The Chronicle of Neurology + Psychiatry Aug 30 2011

by Josh Long,
Assistant Editor, The Chronicle

I
TS TOO SOON to establish
causality, but research has
shown one thing about
obesity and headaches, accord-
ing to an assistant professor at
Johns Hopkins University
School of Medicine.
Obesity and migraine
headaches are related, said
Dr. Lee Peterlin.
Specifically, several studies
have established that obesity
increases the odds of migraine
in reproductive aged women
and men. More recently a
study published in Headache
(April 2011; 51(4):559-569)
which she co-authored with
Dr. Michelle Williams evaluat-
ed the relationship between
weight gain, obesity, and
migraine in over 3,700 pre-
menopausal women.
In this study, women with
migraine as children had a 67
per cent increased risk of gain-
ing 10 or more kgthat is 20
lbs or moreby adulthood as
compared to women who did
not have migraine, she said
Furthermore she said, this
study demonstrated that the
risk of migraine substantially
increased with increasing
severity of obesity. Those
women with class I obesity
(BMI 30-34.9) had a 48%
increased odds of migraine,
Mi g r a i n e
Possible link between
headaches and obesity
n But specialists are unsure of directionality
THE CHRONICLE is commit-
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encouraging green aware
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We are now proud to pro-
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Guest Editorial: Neurosurgical treatment delays ................3
Clinical practices in intimate partner violence ..................15
Canadian Psychiatric Association meeting preview ............16
Canadas National Newspaper of the CNS Sciences nAugust 2011
In this months Chronicle Vitae profile, we talk to Dr.
Steven Cohen, a psychiatrist with Doctors without Borders
who has gone on missions to Chad and the Sudan. He
talks about his travels, his motivation, and the patients he
treated. See page 22
A d d i c t i o n
Smoking while on a low-dose patch
n Patients smoke less and experience fewer cravings
by Josh Long, Assistant Editor, The Chronicle
W
HEN SOME OF HIS schizophrenia patients told him that they were contin-
uing to smoke while on the nicotine patch, Dr. Peter Selby says he
became concerned.
Initially, I got a bit of tachycardia myself, said the head of the nicotine
dependence clinic at the Centre for Addiction and Mental Health in Toronto.
Then he asked his patients how it felt, and they told him that when smoked
while on the patch, they did not want to smoke as
P a t i e n t s a f e t y
Schizophrenia and substance abuse
STATISTICALLY SPEAKING the most at risk population of people
with schizophrenia are those who have comorbid substance
abuse. Dr. Soojin Chun explains the risk factors on page 8.
please turn to page 10
The photograph above comes from a new radiological scanning method using
123
I-ioflupane, which can visually identify dopamine receptor loss. On the left is
a normal brain and on the right is the abnormal brain. please turn to page 12
Diagnosing
Parkinsons Disease
Radiologically
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XEOMIN
science New
Revised Indications
For the treatment of hypertonicity disorders of the 7
th
nerve such as blepharospasm including
benign essential blepharospasm and hemifacial spasm in adults
To reduce the subjective symptoms and objective signs of cervical dystonia (spasmodic torticollis)
in adults
For the treatment of upper limb spasticity associated with stroke in adults

X
E
O
M
I
N

U
P
D
A
T
E
(Clostridium Botulinum Neurotoxin Type A [150 kD],
free from complexing proteins)
INDICATIONS AND CLINICAL USE: XEOMIN
is indicated for the treatment of hypertonicity disorders of the 7th nerve such as blepharospasm including benign essential blepharospasm and hemifacial spasm, upper
limb spasticity associated with stroke, and to reduce the subjective symptoms and objective signs of cervical dystonia (spasmodic torticollis) in adults.
XEOMIN
as a treatment for focal spasticity has been studied in association with usual standard care regimens and is not intended as a replacement for these treatment modalities.
XEOMIN
is not likely to be effective at a joint affected by a xed contracture.

XEOMIN
may only be used by physicians with suitable qualications and proven experience in the application of Botulinum toxin type A and in the use of the necessary equipment, e.g. EMG (electromyography).
CONTRAINDICATIONS: Hypersensitivity to Botulinum neurotoxin type A or to any of the excipients. Generalised disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome). Presence of infection at the
proposed injection site.
Serious Warnings and Precautions
The term unit or U upon which dosing is based, is a specic measurement of toxin activity that is unique to XEOMIN
. Therefore, the unit or U used to describe XEOMIN
activity are different from those used

to describe that of other Botulinum toxin preparations and the units representing XEOMIN
activity are not interchangeable with other products.

Follow the recommended dosage and frequency of administration for XEOMIN
(See product monograph for DOSAGE AND ADMINISTRATION).

General: Patients and caregivers should be advised to seek immediate medical consultation if swallowing, speech, or respiratory disorders arise.
In very rare cases severe adverse events like muscle weakness, dysphagia or aspiration pneumonia with a suspected causal relationship to toxin spread have been reported with the use of botulinum toxin. Also very rare
cases of adverse events with a fatal outcome have been reported. Patients with a neurological underlying disease or swallowing, speech or respiratory difculties have an increased risk for these adverse drug reactions
and should be treated and supervised very carefully.
An anaphylactic reaction may occur rarely after injection of Botulinum neurotoxin type A (See ADVERSE REACTIONS). Adrenaline and other medical aids for treating anaphylaxis should be available.
Extra caution is required when injecting at sites close to sensitive structures such as the carotid artery and lung apices.
XEOMIN
should be used with caution: in patients suffering from amyotrophic lateral sclerosis or other diseases which result in peripheral neuromuscular dysfunction; in targeted muscles which display pronounced
weakness or atrophy. Spasmodic torticollis: Patients should be informed that injections of XEOMIN
for the management of spasmodic torticollis may cause mild to severe dysphagia with the risk of aspiration and
dyspnoea. Dysphagia can last for up to two to three weeks after injection. Patients with smaller neck muscle mass, or patients who require bilateral injections into the sternocleidomastoid muscles are at greater risk.
The occurrence of dysphagia is attributable to the spread of the pharmacological effect of Botulinum toxin as the result of the neurotoxin spread into the oesophageal musculature.
Please see product monograph for full warnings, precautions, adverse events and patient selection criteria
To report an adverse reaction please notify Health Canada at 1-866-234-2345 or MERZ Canada at 1-866-815-8715.
XEOMIN
is a registered trademark of Merz GmbH. Full product monograph available on request by contacting Merz Pharma Canada Ltd. at 1-877-811-6379.
XEOMIN
is a registered trademark of Merz GmbH.

See Prescribing Summary on page 19

benig
For th

osp r gn essential blepha
eatment of hyperto r he t

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pasm in adults
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N I M O E X
o s s a y t i c i t s a p s b m i l
N A S N O I T AAT C I D N I

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i d i d t b h t i i t l f f t t
e v i t c e j b u s e h t e c u d e r o t d n a , e k o r t s h t i w d e t a i c o
r o f d e t a c i d n i s i
N I M O E X : E S U L A C I N I L C D N

limb spasticity associat
mptoms and objective s
i d d t l h t i i t i
t s y d l a c i v r e c f o s n g i s e v i t c e j b o d n a s m o t p m y s e
7 e h t f o s r e d r o s i d y t i c i n o t r e p y h f o t n e m t a e r t e h t

oke in adult r ted with st
signs of cervical dyston
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t h t f t l d d t i t i d
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e b g n i d u l c n i m s a p s o r a h p e l b s a h c u s e v r e n h t 7

ts
nia (spasmodic torticoll
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Prescribing Summary ee

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r e p p u , m s a p s

o c e r e h t w o l l o F
t a h t e b i r c s e d o t
t i n u m r e t e h T
i n r a W s u o i r e S
n o i t c e j n i d e s o p o r p
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k i l t o n s i
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t a e r t a s a
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i t a r t s i n i m d a f o y c n e u q e r f d n a e g a s o d d e d n e m m
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s n o i t u a c e r P d n a s g n
. e t i s
t n i x o t o r u e n m u n i l u t o B o t y t i v i t i s n e s r e p y H : S N O
i t a c i l a u q e l b a t i u s h t i w s n a i c i s y h p y b d e s u e b y
o c d e x a y b d e t c e f f a t n i o j a t a e v i t c e f f e e b o t y l e
s a n i d e i d u t s n e e b s a h y t i c i t s a p s l a c o f r o f t n e m t
e s o t d e s i v d a e b d l u o h s s r e v i g e r a c d n a s

D r o f h p a r g o n o m t c u d o r p e e S (
NN
I M O E X r o f n o i
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. ) N O I T AAT R T S I N I M D A D N A E G A S O D
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o t d e s u U r o t i n u e h t , e r o f e r e h T .
NN
I M O E X o
r g a i n e h t s a y m . g . e ( y tty i v i t c a e l c s u m f o s r e d r o s i d
n e h t f o e s u e h t n i d n a A e p y t n i x o t m u n i l u t o B f o
e r t e s e h t r o f t n e m e c a l p e r a s a d e d n e t n i t o n s i d n
r o s i d y r o t a r i p s e r r o h c e e p s g n i w o l l a w s

o h t m o r f t n e r e f f i d e r a y tty i v i t c a
N I M O E X e b i r c s e d
n i f o e c n e s e r P . ) e m o r d n y s n o t a E - t r e b m a L , s i v a
p a r g o y m o r t c e l e ( G M E . g . e , t n e m p i u q e y r a s s e c e
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a e r c i t c a l y h p a n a n A
e t a e r t e b d l u o h s d n a
v e e s r e v d a f o s e s a c
e s s e s a c e r a r y r e v n I
t n e i t a P : l a r e n e G

6 6 8 - 1 t a a d a n a C h t l a e H y f i t o n e s a e l p n o i t c a e r e
e v d a , s n o i t u a c e r p , s g n i n r a w l l u f r o f h p a r g o n o m
a h p e h t f o d a e r p s e h t o t e l b a t u b i r t t a s i a i g a h p s y d
e j n i r e t f a s k e e w e e r h t o t o w t o t p u r o f t s a l n a c a i g
o f n i e b d l u o h s s t n e i t a P : s i l l o c i t r o t c i d o m s a p S . y
a m o r f g n i r e f f u s s t n e i t a p n i : n o i t u a c h t i w d e s u e b
s e v i t i s n e s o t e s o l c s e t i s t a g n i t c e j n i n e h w d e r i u
n i l u t o B f o n o i t c e j n i r e t f a y l e r a r r u c c o y a m n o i t c a
. y l l u f e r a c y r e v d e s i v r e p u s d n a d e
P . d e t r o p e r n e e b e v a h e m o c t u o l a t a f a h t i w s t n e
s y d , s s e n k a e w e l c s u m e k i l s t n e v e e s r e v d a e r e v e
e s o t d e s i v d a e b d l u o h s s r e v i g e r a c d n a s

1 7 8 - 5 1 8 - 6 6 8 - 1 t a a d a n a C Z R E M r o 5 4 3 2 - 4 3 2 - 6
a i r e t i r c n o i t c e l e s t n e i t a p d n a s t n e v e e s r e
r e h t s a n i x o t m u n i l u t o B f o t c e f f e l a c i g o l o c a m r a
s s a m e l c s u m k c e n r e l l a m s h t i w s t n e i t a P . n o i t c e
a n a m e h t r o f
NN
I M O E X f o s n o i t c e j n i t a h t d e m r o
s e s a e s i d r e h t o r o s i s o r e l c s l a r e t a l c i h p o r t o y m a
p a g n u l d n a y r e t r a d i t o r a c e h t s a h c u s s e r u t c u r t s
O I T C A E R E S R E V D A e e S ( A e p y t n i x o t o r u e n m u
e s a e s i d g n i y l r e d n u l a c i g o l o r u e n a h t i w s t n e i t a P
c e p s u s a h t i w a i n o m u e n p n o i t a r i p s a r o a i g a h p s
s f i n o i t a t l u s n o c l a c i d e m e t a i d e m m i k e e

. 5 1
a h p o s e o e h t o t n i d a e r p s n i x o t o r u e n e h t f o t l u s e r
o t n i s n o i t c e j n i l a r e t a l i b e r i u q e r o h w s t n e i t a p r o , s
i m e s u a c y a m s i l l o c i t r o t c i d o m s a p s f o t n e m e g a
u f s y d r a l u c s u m o r u e n l a r e hhe p i r e p n i t l u s e r h c i h w
. s e c i p
a e r t r o f s d i a l a c i d e m r e h t o d n a e n i l a n e r d A . ) S N O
s e i t l u c f i d y r o t a r i p s e r r o h c e e p s , g n i w o l l a w s r o
e e b e v a h d a e r p s n i x o t o t p i h s n o i t a l e r l a s u a c d e t c
r o s i d y r o t a r i p s e r r o , h c e e p s , g n i w o l l a w s

. e r u t a l u c s u m l a e g
e t a e r g t a e r a s e l c s u m d i o t s a m o d i e l c o n r e t s e h t o
o i t a r i p s a f o k s i r e h t h t i w a i g a h p s y d e r e v e s o t d l
n o r p y a l p s i d h c i h w s e l c s u m d e t e g r a t n i ; n o i t c n
. e l b a l i a v a e b d l u o h s s i x a l y h p a n a g n i t a
r g u r d e s r e v d a e s e h t r o f k s i r d e s a e r c n i n a e v a h s
s l A . n i x o t m u n i l u t o b f o e s u e h t h t i w d e t r o p e r n e
. e s i r a s r e d r

. k s i r r e
d n a n
d e c n u o
s n o i t c a e r
e r a r y r e v o s

s i g e r a s i
N I M O E X
e t s i g e r a s i
N I M O E X

o m t c u d o r p l l u F . H b m G z r e M f o k r a m e d a r t d e r e t s
. H b m G z r e M f o k r a m e d a r t d e r

r e M g n i t c a t n o c y b t s e u q e r n o e l b a l i a v a h p a r g o n o

. 9 7 3 6 - 1 1 8 - 7 7 8 - 1 t a . d t L a d a n a C a m r a h P z

ote rro om complexing p r ee f r f
(Clostridium Botulinum Neu

eins)
, A [150 kD] ype TTy otoxin r
Dr. Klimeks letter to the Ontario Minister of Health and Long-Term Care
T
he consequences of acute neurologic catastrophe are
devastating and ample evidence demonstrates that the
best care for patients is timely care, but given the
scarcity of resources this is not always what we are able to
provide for our patients.
As a neurologist in a community setting, my
first catastrophe sent out of country for emer-
gent care occurred in July 2006. Since my
letter to then Ontario Health Minister
George Smitherman, the Ministry of
Health and Long-term Care recog-
nized the reduced surge capacity to
deal with catastrophes. In 2008-09,
120 patients went out of country
for neurosurgery. In 2009-10, 202
patients went out of country. The
most recent data I heard was 50
patients were sent to the U.S. for
this purpose alone this last year.
Family members of a patients of
mine said 12 Canadians were also
treated in the same U.S. facility.
Several studies and interviews
at high levels promised improve-
ment. Now we have a 24 hour tele-
phone CritiCal network available,
complete with preprinted forms, for
emergent out-of-country transfer to pre-
ferred providers offering prenegotiated dis-
count service invoiced to the Ontario government.
Health Minister Deborah Matthews admits, The member
opposite is absolutely right: There has been a dramatic
increase in out-of-country health care provided and covered
through OHIP. (Hansard, Nov. 26, 2011). Maybe this is
effective cost reduction. If so, the cheapest form of care is
neglect and comes with an immensely personal cost.
If we dont inform the public, and the patient, that the
best care may not be available in Ontario, then we are not
defending ourselves or fully informing the person consenting
to the care proposed. But should we do so, then we generate
more (CYA) nonmedical activity or risk allegations of unpro-
fessionalism in commenting on the availability of others (or
other centres).
This is particularly true if treatment else-
where is not equivalent or identical to treat-
ment in Ontario and the proposed treat-
ment is not available anywhere in
Ontario. Cases in the public domain
brought before the Health Services
Appeal and Review Board (HSARB)
by educated and persistent patients
have shown the magnitude of the
problem. It is clear in the findings
of the HSARB that patients are
obliged to seek care across the
border for which OHIP must pay.
(File # 10-HIA-0063 Health
Services Appeal and Review
Board, Oct. 27, 2010 Toronto)
Simultaneously health care
providers are considered technical
experts and agents responsible for
implementing a social policy of
rationing and delayed care. Any MD has
difficulty defending a foreseeable and pre-
ventable adverse outcome. It is compounded
if one is also held to a standard of care which pre-
sumes infrastructural shortage is an inadequate defense, no
attempt has been made to correct it and no immunity is
granted for acting as an agent of social policy in rationing
care.
Dr. Edwin Klimek is president of the Association of Ontario Neurologists
and operates a neurology practice in St. Catharines, Ont.
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Volume 14, Number 3, published August 2011
ISSN 1209-0565
Guest editorial: Treatment delayed is treatment denied
THIS LETTER IS directed to several who may
be in a position of authority to correct a
remediable and foreseeable problem, and
the Minister of Health and Long-term Care
of Ontario specifically. It is unclear to me
who has the greatest burden for shared
responsibility (hospital, LHIN, province) in
the neurosurgical infrastructure of Ontario.
Vignette 1
On July 5, 2006, Mr. X, a 47-year-old,
arrived 10 a.m. in the office with an overt spastic para-
paresis of subacute onset. He used a cane and was bare-
ly ambulatory. A symptomatic navel level was noted with
sphincter involvement.
The required emergent MRI scan was scheduled for
noon after telephone solicitation. Unable to lie adequate-
ly motionless due to pain, he was sedated in ER. A
second effort proved diagnostic by 2:30 of a tho-
racic spine central posterior disc herniation with a
lunate crescent of residual spinal cord visible.
After engaging Critical in futile hours of can-
vassing the province for emergent neurosurgical
assistance, the case was transferred out-of-coun-
try by 8 p.m. for definitive immediate neurosurgical
management. Faxing of paper work for out of
country treatment approval occurs at 9 pm.
Homeland Security required documentation of citizenship
without a criminal record.
Vignette 2
Mr. X, a 39-year-old man, experiences an injury to the
neck and is confirmed to have a fractured spine. The
emergency room seeks advice on management and is
advised that patient needs surgical stabilization at region-
al spine centre, but there are no beds. Patient is held
over. He is found on the morning of the 3rd day awaiting
transfer in hospital not moving legs.
These vignettes taken from professional practice in St.
Catharines demonstrate that patients suffer from neuro-
surgical infrastructural inadequacies in Ontario and this
results in transfer of patients to the United States. By any
estimate, the cost of long term care of the latter unfortu-
nate man exceeds the cost of the definitive care he was
denied. Surely, either individuals loss of societal contri-
bution alone should persuade anyone the current inade-
quate neurosurgical infrastructure is not in societys best
interest.
See the Ontario Association of Neurologists
website at http://www.aoneuro.on.ca
Dr. Edwin Klimek
August 2011 n3
I spend a lot of my time trying to draw the attention of actors to the minute and
subtle details of human behavior, which was the sort of thing I was looking at when
I was a neurologist. Jonathan Miller
I n t h e n e ws
n In the London [Ont.] Free Press, Dr.
Klimek talks about the problems
hes experienced with CritiCall,
including what he calls an inabili-
ty to keep track of empty beds,
and how patients entering the
U.S. for surgery must still be
cleared by Homeland Security
and have a valid passport to
enter.
Read this London Free Press
article at http://ow.ly/4WpHg
nIf Alzheimers disease grows at the
rate predicted by the Alzheimers
Society, that is 40% in 10 years,
Dr. Klimek says this single disor-
der will take up the time of every
neurologist in Ontario. This was
part of a presentation made on
Jan. 24, 2011 to the Standing
Committee on Finance and
Economic Affairs. He also said
that though additional services
had been supported, they had not
been funded.
Read Dr. Klimeks Hansard
excerpt in the St. Catharines
Standard at http://ow.ly/4WoNl
n In a CBC interview, Dr. Klimek esti-
mates that the cost of sending
patients to the U.S. costs Canada
over $100 million a year. Though he
says hes been writing letters about
this for years, hes seen little action.
Read the CBC article at
http://ow.ly/4WqLB
N

P
n
PARALYZED WITH AN INJURY to his spinal
cord from C7-T1, Rob Summers is now
able to stand with the help of electrical
stimulation to the spinal cord, according
to The Lancet (May 20, 2011).
Epidural stimulation enabled the
man to achieve full weight-bearing
standing with assistance provided only
for balance for 4-25 minutes, wrote the
authors.
The patient achieved this standing
during stimulation using parameters
identified as specific for standing while
providing bilateral load-bearing proprio-
ceptive input. We also noted locomotor-
like patterns when stimulation parame-
ters were optimized for stepping.
MedPage Today reports that Summers
was struck by a hit-and-run driver and
was unable to walk due to the spinal
cord injury he received, and that since
the device was implanted in December
of 2006, he has regained control of his
bladder, sexual functioning, and the abil-
ity to regulate his body temperature.
His ability to carry his own weight has
also improved. Though he was initially
only able to carry 65% of his weight, he
may now carry all of it with the assis-
tance of balance aids.
Reggie Edgerton, PhD, was one of
the researchers who worked on this ther-
apy. He told National Public Radio that
seeing Summers move his legs was a big
surprise.
This demonstrates that you can
regain voluntary control, Dr. Edgerton
said, but the voluntary control is only
regained in the presence of stimulation.
So far, the device implanted into
Summers is only active about two hours
a day, but he did say that there are linger-
ing effects when the device is not acti-
vated, including increased feeling.
I had a shot in my lower back just
the other day as part of a check-up and
I felt the entire thingthe needle go in,
the pain, everything, he said. So that
was both good and bad, exciting to
experience that again, but knowing that I
continue to make progress is very excit-
ing.
Read this Lancet article
at http://ow.ly/51DCv
4 nAugust 2011
Neurology Editor
Richard Gladstone,
MD, FRCPC
Psychiatry Editor
J. J. Warsh, MD, FRCPC
Editor, Innovation in the Mind Sciences
Roger S. McIntyre,
MD, FRCPC
Editorial Director
R. Allan Ryan
Senior Associate Editor
Lynn Bradshaw
Assistant Editor
Josh Long
Publisher
Mitchell Shannon
Sales Director
Peter M. Stamp
Production and Circulation
Cathy Dusome
Comptroller
Rose Arciero
sAtelier:
The artist who created this work is 90 years of age, and has experienced a
stroke. She can only use her right dominant hand.
She is restricted to a wheelchair, and she takes medication for depression.
Esther Zeller, her art therapist, says that this client considers her atwork to be
an outlet for extreme sadness of her personal, physical, and emotional challenges.
There is little conversation between us, said Zeller, but she feels enabled,
valued and determined to share her emotions as expressed through her art.
More information on Esther Zeller and her work in art therapy is available at
www.artdynamics.ca
sQuick-start guide to The Chronicle, August 2011:
Conference Index
Ontario Psychiatric Association Smoking while on the patch (p.1),
Substance abuse puts schizophrenia patients at risk (p. 8), Treating sub-
stance abuse in schizophrenia (p. 9)
American Academy of Neurology: New adjunct diagnostic tool for
Parkinsons examined by Dr. Frederick Weiland (p. 12)
Canadian Psychiatric Association: Conference preview (p. 16)
Chronicle Vitae: Overseas psychiatry (p. 22)
SEV
to
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Electrical spinal stimulation puts man back on his feet
n Patient with paraplegia able to walk using electrical stimulation, and has returned sensation
by Jo
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Parental Alienation Syndrome and the DSM-5
n DSM-5 working group says insufficient evidence to classify condition as a mental disorder
erton
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August 2011 n5
Attempts have been made to educate psychiatrists about
adult ADHD, but many doctors still dont believe in it.
Dr. Umesh Jain, an ADHD researcher at Toronto's Centre for
Addiction and Mental Health
I n t h e n e ws . . .
nQuestions were raised regarding the
ethics and efficacy of behaviour
modification in prisons. Not only is
this treatment unethical and inef-
fectual in the real world, not only is
its refusal to see the underlying
causes tantamount to professional
negligencethis form of treatment
undoubtedly exacerbates certain
forms of mental illness, while caus-
ing others, wrote Dave Holmes,
PhD, and University Research
Chair in Forensic Nursing at the
University of Ottawa in the
Journal of Nursing Management
(April 2011; 19(3):293301). He
says this is because it treats
prisoners like children. Forensic
psychiatrist Dr. Adekunle Garba
Ahmed disagreed, saying that the
repeat offender rates are much
lower at prisons that use this pro-
gram, and that Dr. Holmes study
places too much emphais on
social scientists rather than psy-
chological studies.
Read this original study at
http://ow.ly/51ILo
n The link between suicide and native
North Americans may be purely
incidental. When controlling for
mental illness, suicide was found
to be no more prevalent in this
group than in the general popula-
tion, says Shay-Lee Bolton, PhD,
of the University of Manitoba in
Winnipeg. This research was pre-
sented during an oral session at
the American Psychiatric
Association meeting in Honolulu,
Hawaii.
Read this article at
http://ow.ly/51Mz6
O n t h e we b
nThought-controlled video games are
being explored as a possible ther-
apy for ADHD. Its a very innova-
tive strategy, said CAMH psychia-
trist Dr. Umesh Jain, who is cur-
rently in the process of applying for
a grant to fund this research. The
idea is to use technology being
developed by the Toronto-based
company, Interaxon. In this sys-
tem, a gamer wears a headband
with sensors that monitor their
brain waves. Dr. Jain still questions
whether this will enhance attention
skills when not playing the game.
Read the CBC article at
http://ow.ly/51NtB
ub-
SEVERAL PERSPECTIVES OVER whether
to include alienation syndrome in the
DSM-5 were expressed on the CBC
radio program, The Current (May 17,
2011).
Dr. Rachel Klein, a member of the
DSM-5 Child and Adolescent Working
Group, said that it was unlikely to be
included as a mental disorder.
There are [many] clinical anec-
dotes but thats insufficient for inclu-
sion in the [DSM]. said Dr. Klein..
I want to add that I think its real-
ly real, that it happens, its a big prob-
lem. The question is whether it reflects
mental dysfunction.
Joseph Goldberg, the founder of
the Canadian Symposium for
Parental Alienation Syndrome, dis-
agreed that there was no scientific
evidence to support the idea that
parental alienation syndrome exists
as a mental disorder, and that it
should be considered a mental disor-
der in the DSM-5.
What makes this a mental disorder
is that they have a gradual denegation
of the parent they were once bonded
to, he said. Thats different than
when a child rejects a parent for legiti-
mate reasons.
Opposed the inclusion of this syn-
drome in the DSM-5 is Terry ONeill,
the President of the National
Organization for Women.
The problem with this so-called
syndrome is that it confuses law and
policy with medicine, she said.
Treatment requires cutting off con-
tact with the preferred parent and put
ing the child into the custody of the
rejected parent, ONeill said,
Classifying parental alienation syn-
drome as a mental disorder could lead
to children being misdiagnosed with
parental alienation syndrome when they
could have a legitimate reason for
rejecting one parent, either due to abuse
or neglect.
ONeill said that frequently in
divorce cases where a child rejects a
parent, the situation resolves itself
after two years and the child often
expresses remorse for their actions.
Listen to the show online
on the CBC website at
http://ow.ly/5A1l8
n
U
NIVERSITY OF TORONTO students have developed a speech
enabling mobile phone application called MyVoice that
will allow people who are unable to speak to communicate.
Freely available,
the program offers
users a more cost
effective option to
find out if the prod-
uct suits their needs.
When we met
users and read sto-
ries about the com-
munities that use the
aids that we com-
pare with, weve
heard something
that we found par-
ticularly troubling.
That was a phenom-
enon where people
took a leap of faith
into a device, spend-
ing $10,000 or
$12,000, and finding
three or six months
later that it wasnt
the right device for
that person, said
Alexander Levy, the creator and lead researcher on the proj-
ect.
Once the money is spent, either by the purchaser or
through a possible government subsidy program, he said,
they were effectively committed to a product that may not
have been the most suitable.
By contrast, MyVoice is free, though Levy says that there
will be a $30 a month subscription fee later for people who
want premium services added.
In the meantime, the free version of the MyVoice applica-
tion allows the user to prepare phrases according to common
situations and uses the GPS feature now available in many
mobile phones, a
feature that they
call location
awareness.
L o c a t i o n
awareness is a
feature which
a ut oma t i c a l l y
provides words
and phrases
based on where
you are, said
Levy. One
example, very
Canadian, is if
you walk into
Tim Hortons the
words Timbits
and double-dou-
ble could auto-
matically come
onto the screen if
you tag them to
do so. This
means easier,
more comfort-
able communication for people with speech and language
challenges.
Users can create a customized vocabulary if, for example,
they regularly order their coffee as half decaf and half regu-
lar. They also have access to specialized vocabulary lists
Giving the voiceless a voice through new technology
n Text-to-speech software allows aphasiacs to speak through their smartphones
Aakash Sahney (left) and Alexander Levy (right) discuss their smartphone
application for people unable to speak
by Lo
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much, he said at the Ontario
Psychiatric Associations 91st annual meeting in Toronto.
Dr. Selby says it is because with the steady dose of nicotine
provided by the patch, the patient no longer experienced the
dopaminergic effect implicated in addictive response to nico-
tine they once received when they smoked.
PUTTING NICOTINE ADDICTION IN PERSPECTIVE
Any drug you inhale is more addictive than anything you inject,
he said. Think about it. It goes straight to your lungs, straight to
your right, left atrium, left ventricle, and
through your carotids to your brain. It
takes seven to thirty seconds to hit your
brain and release dopamine.
It also bypasses the first pass metab-
olism in the liver, so that a higher drug
level is delivered through the respirato-
ry route versus the injected route.
Thats with every puff, he says. And
with an average cigarette taking about 10
puffs to finish, Dr. Selby said a person
smoking 20 cigarettes a day would take
200 puffs per day. Each puff would be a
positive reinforcement to continue smok-
ing. Its part of the reason that he says
smoking is such an addictive behaviour.
In essence that behaviour has been rewarded more than
eating, sex, voiding, you name it, he said.
And so, he said, taking a drag of a cigarette remains a
strongly conditioned response.
When the patient cant have a cigarette because of their
nicotine patch dosage, the patient has a choice. Stay on the
patch and have no way to safely satisfy their cravings, or give
up the patch to give in to the craving.
Guess what happens? Because they are in a personified
relationship with the cigarette, the new kid on the block comes
off, said Dr. Selby, and patients switch back to cigarettes.
In traditional nicotine therapy, patients start with a high
dose patch and titrate until they dont need a patch at all. Dr.
Selby has turned that approach on its head, starting the patient
on a low dose patch and gradually increasing the dose until the
patient no longer wants to smoke, and then titrating down
after six weeks over a four week period.
Weve got to figure out how to get the dose of nicotine to
the level where if you have a cigarette with it, youre going to
say, The cigarette doesnt do anything, he said.
In an interview with THE CHRONICLE, Dr. Selby explained
the role pharmacological interventions can play.
He first said that nicotine replacement therapy makes sense
as first-line treatment because the patient has already demon-
strated that nicotine is well-tolerated.
Still, other pharmacological interventions may be helpful,
he said, if nicotine replacement therapy has not had the
desired effect after four weeks of treatment. However, any
level of success requires careful analysis, he said, which he
calls more art than science.
In the case of a partial
response to treatment, Dr. Selby
said that it may be necessary to
tweak the treatment.
If they say theyre smoking
steady, like seven cigarettes a day
[...] then we may boost their dosage
[of nicotine replacement therapy]
by seven milligrams, he said.
ANALYSING EFFECTIVENESS
Finding the best approach
requires an assessment of the
environmental factors that may
cause the patient to smoke. These
factors may affect the patients success but can be remedied by
a change in the environment, or other non-pharmacological
techniques, he said, adding that. if the patient says they smoke
in response to a stress trigger, an inhaler or nicotine gum
might be a viable option to consider.
On the other hand, if they say they have to smoke ten or
twenty cigarettes on top of the patch, then we know the treat-
ment isnt working, said Dr. Selby.
And then you make a decisionare you going to up the
dose, add a medication or switch?
Bupropion is effective in tobacco cessation among patients
with comorbid mental illness, is well-tolerated, and compati-
ble with nicotine replacement therapy.
But you have to be careful in people with [mania in bipo-
lar disorder] because you may precipitate a manic episode, he
said, regarding bupropion.
So you can use it in people with [bipolar disorder] but you
[have to] make sure theyre stable and they have their mood
stabilizers in place.
Dr. Selby says if nicotine replacement doesnt work, hes
Low-dose nicotine patch as first line treatment
6 nAugust 2011
C l i n i c a l T r i a l s
n While bupropion has been shown to
double quit rates, an Ontario study
aims to determine whether if cost of
this medication could be a barrier to
patients. The study seeks volunteers
over the age of 18 who smoke 10 or
more cigarettes a day who have not
enrolled in any of the STOP study
NRT models in the last six months.
Subjects will be given bupropion
(150 mg) for up to eight weeks, sup-
plemented by brief individual coun-
selling sessions focused on smoking
cessation and relapse prevention.
Contact: Centre for Addiction and
Mental Health, Laurie Zawertailo,
PhD, 416-535-8501 ext 7422, lau-
rie_zawertailo@camh.net
More info on
this clinical study
at http://ow.ly/5NKxG
#Any drug you #Any drug you
inhale is more inhale is more
addictive than addictive than
anything you anything you
inject" inject"
DSM-5 distinguishes between addiction and dependence
ADDICTION IS BEING redefined in the DSM-5 according to an article
in Addiction (May 2011: 106(5):866867).
The term dependence, while used in past decades to refer
to uncontrolled drug-seeking behavior, has an alternative mean-
ingthe physiological adaptation that occurs when medications
acting on the central nervous system are ingested with rebound
when the medication is abruptly discontinued, wrote Charles
OBrien, MD, PhD.
The authors said the dual meanings led to confusion, and may
have resulted in under treatment of pain as physicians fear creat-
ing a physical addiction in their patients by prescribing opioids.
The DSM-5 seeks to address this problem in a chapter called
addiction and related disorders.
Dr. OBrien says that the criteria for diagnosis will remain sim-
ilar but for the removal of the committing illegal acts.
In its place will be the addition of craving to the criteria.
The other major change relates to the elimination of the
abuse/dependence dichotomy, given the lack of data supporting
an intermediate stage, he wrote.
These changes are anticipated to improve clarification and
diagnosis and treatment of substance use and related disorders.
Read the study at http://ow.ly/5WlhF
continued from page 1
by Louise Gagnon,
Correspondent, The Chronicle
U
NDERSTANDING THE
neurological basis for
drug addiction may lead
to possible treatments for
drug addiction, according to a
researcher at Queens
University in Kingston, Ont.
We know some of the risk
factors for drug addiction,
such as stress at an early age or
exposure
to a trau-
m a t i c
envi ron-
ment, has
a huge
effect on
your sus-
ceptibility
to devel-
op a drug abuse problem later
in life, said Eric Dumont,
PhD, an assistant professor in
the department of anesthesi-
ology at Queens.
Speaking at a neurosciences
seminar in Toronto highlight-
ing neurological research proj-
ects where Canada and France
are collaborating, Dr. Dumont
said he and co-investigators
are aiming to identify mecha-
nisms that are distinctly linked
with drug-taking behaviour.
They are performing similar
experiments to confirm find-
ings and are working in a com-
plementary fashion, he said.
We want to be able to spare
natural motivations to allow
someone to operate normally,
he said. We could reduce
motivations that affect drug-
taking behaviour, but it will
also affect motivations such as
wanting to feed ones self.
Specifically, Dr. Dumont
and his collaborators have
identified that Src, a non-
receptor tyrosine kinase, plays
a part in drug-taking behav-
iours in animal models.
Tyrosine kinases play crucial
roles in signalling between
cells in multi-cellular animals.
We see these src tyrosine
kinases as only contributing to
drug-taking behaviours in ani-
mals that have been chronical-
ly taken psychostimulants like
cocaine or methampheta-
mine, said Dr. Dumont.
This target is uniquely associ-
ated with drug-taking behav-
iour, and it has nothing to do
with normal motivation.
Src tyrosine kinase (STK)
inhibitors are being explored
in clinical trials as treatment
for various cancers, he said,
which means that a safety pro-
file of the drug is available.
This may speed up
attempts at using them to treat
addiction behaviours,said Dr.
Dumont, who added that as of
now there is no evidence that
this drug can be abused.
Dr. Dumont says a poten-
tial therapy using STK
inhibitors would assist in curb-
ing the use of not only illicit
psychostimulants such as
cocaine, but also keep a lid on
Understanding mechanisms of addiction could lead to new therapies
n Queens University researcher says that research could disable reward response and avoid addiction in opioid treatments
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P
EOPLE WITH SCHIZOPHRENIA are at significantly greater
risk for violence and self harm when they have comor-
bid substance abuse, according to research presented at
the annual meeting of the Ontario Psychiatric Association.
The rate of violence is about 8% among schizophrenia out-
patients but 30% when combined with substance abuse, accord-
ing to Dr. Soojin Chun of The Ottawa Hospital, referring to a
study in Hospital and Community Psychiatry
(July 1990; 41:761-770).
Dr. Chun also cited a report in the
journal Progress in Neuro-Psychopharmacology
and Biological Psychiatry (June 2006;
30(4):586-598), which identified possible
risk factors for violence and aggression as
males, between the ages of 15 and 24,
who are unemployed, have little education, and often have
organic syndrome and exhibit substance use. Clinical features
for violence and aggression from this study included common
auditory hallucination, and paranoid delusions seen in psy-
chotic disorders.
In theory, if no substance [abuse] was involved, the rate of
violence or aggression in psychiatric patients is actually almost
[the] same as [the] general population, she said, referring to a
study (Arch Gen Psychiatry May 1998; 55(5):393-401).
However when there is substance use, the rate can triple
or even quadruple.
HARM TO SELF
Aside from harm to others, Dr. Chun also said that there was
greater risk of self harm in schizophrenia patients who engage
in substance abuse.
Identifying the groups most likely
to commit suicide, Dr. Chun said
that it varied by gender.
For males, suicide is more likely to
occur in youths with schizophrenia,
while for females the most likely is a
mid-aged single divorced women
with a mood disorder.
Ninety per cent of suicides are
committed by people with [a] docu-
mented mental illness or substance use
problem, she said.
Among conditions commonly
found in patients with safety issues
were, most commonly, primary mood
disorders, including bipolar affective disorder and major depres-
sive disorder. Schizophrenia was the second most common diag-
nosis, and the third included delirium, dementia, and other cog-
nitive disorders.
Read more on schizophrenia
and patient safety at http://ow.ly/605fY
Substance abuse puts schizophrenia patients at risk
n Psychiatrist suggests that treating comorbid drug addiction would improve quality of life
SEEKING TO FIND the mechanisms that cause malfunctions of working memory, semantics, prediction error,
and dopamine neuromodulation in schizophrenia, the researchers of a study published in Biological
Psychiatry created an artificial neural network model and tested it for narrative understanding and recall
(May 15, 2011; 69(10):997-1005).
Findings suggest that exaggerated prediction-error signalling in schizophrenia intermingles and cor-
rupts narrative memories when incorporated into long-term storage, thereby disrupting narrative language
and producing fixed delusional narratives, concluded the authors. If further validated by clinical studies,
these computational patients could provide a platform for developing and testing novel treatments.
In the study, an artificial neural network learned sets of autobiographical and impersonal crime sto-
ries with associated emotion coding. The authors then compared these eight illness mechanisms against
subjects with schizophrenia or schizoaffective patients using a delayed story recall task. Control subjects
also completed the task.
One of the authors of the study, Dr. Ralph Hoffman of Yale University in New Haven, Conn. explained
what they learned from this experiment on National Public Radios Science Friday.
What surfaced was a clear cut, at least a statistical winner, said Dr. Hoffman. And that was what we
now term as hyperlearning.
What this means, he says, is that when the simulated neural network modules were engaged in a
learning processin this case learning the previously described crime storiesthe errors that occurred
in the simulation were similar to those that were created by schizophrenics.
If this memory consolidation process was accelerated to an excessive degree that the system began
to confuse different stories or memories and to corrupt these representations in very specific ways, he
said, it seemed to be suggestive of certain language manifestations of schizophrenia.
Read this article in
Biological Psychiatry at http://ow.ly/52B2M
A possible mechanism of schizophrenia
Un
W
T
n
New quetiapine label in U.S.
n Includes more detail on associated heart risks
ASTRAZENECA REVISED the label for quetiapine in mid-July for the
U.S. market, as requested by the FDA.
The passage added to the label is as follows:
The use of quetiapine should be avoided in combination with
other drugs that are known to prolong QTc including Class 1A
antiarrythmics (e.g., quinidine, procainamide) or Class III antiarryth-
mics (e.g., amiodarone, sotalol), antipsychotic medications (e.g.,
ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gati-
floxacin, moxifloxacin), or any other class of medications known to
prolong the QTc interval (e.g., pentamidine, levomethadyl acetate,
methadone).
In a New York Times interview (July 19, 2011), AstraZeneca
spokeswoman Stephanie Andrzejewski said the new warning will
provide additional guidance to physicians treating patients at risk
for QT prolongation. While the old label had mentioned the risk of
a prolonged QT, she said it was not as specific as the current label.
The product information sheet issued by Health Canada for
quetiapine was last updated in April 2008.
It says: Because of its potential for inducing hypotension, que-
tiapine may enhance the effects of certain antihypertensive agents.
Read all about it at http://nyti.ms/pe3fqy
Dr. Soojin Chun, at the Ontario Psychiatric
Association meeting
8 nAugust 2011
#Ninety per cent of
suicides are committed by
people with a documented
mental illness or substance
use problem"
A
LCOHOL ADDICTION IN patients with comorbid schizo-
phrenia tends to have a high relapse rate, as well as detri-
mental effects on schizophrenia-related outcomes. Dr.
Shaul Lev-Ran from the Centre for Addiction and Mental
Health reviewed pharmaceutical options to improve the odds at
the Ontario Psychiatric Association annual meeting in Toronto.
A medication that seems to stick
out, says Dr. Lev-Ran, is clozapine.
[Its] particularly good for treating
schizophrenia patients with substance use
disorders and there are a number of case
reports and case series that show quite
dramatic results when schizophrenia
patients with co-morbid substance use
disorders are treated with clozapine, he
said. In one of those studies they were
twice as likely to have remission of their alcohol-use disorder.
As well, he said that a 10-year study, published in the
Schizophrenia Bulletin (July 2000; 26(2):441-449), had found
patients on clozapine had lower relapse rates.
Most studies reporting that clozapine treatment is associated
with remission of substance use disorders in schizophrenia
patients are retrospective, he said, but just recently there was an
RCT showing its efficacy in reducing cannabis smoking among
schizophrenia patients with cannabis use disorders, he said,
referring to a study published in the Journal of Dual Diagnosis
(May 2011; 7(1-2): 50-63) that was led by Mary F. Brunette.
Depot antipsychotics, also called long acting injections, have
also shown promise. There are a few studies of depot antipsy-
chotics, he said, where schizophrenia patients decreased their
alcohol use. He added that part of the improvement in alcohol
use outcomes can be attributed to improved compliance to
treatment and reduced symptoms of schizophrenia.
There is also some evidence that long acting risperidone
is more effective than first generation antipsychotics, though
this has been shown in schizophrenia patients with sub-
stance use disorders in general, and not specifically for alco-
hol dependence.
Approved pharmacological treatments for alcoholism in
the general population have also been found to be effective
at treating alcoholism in schizophrenia, he said, particularly
disufiram and naltrexone.
Disulfiram is actually somewhat surprising as clinicians have
been afraid to use it in people with schizophrenia because of
fear that it might increase psychosis, he said, adding that this is
mainly due to clinical reports in the 1970s when the doses of
disulfiram used were much higher than those suggested today.
Recent reports have shown that disulfiram may be safe in indi-
viduals with psychiatric disorders, including schizophrenia.
Naltrexone, he said, appears to be both efficacious and
safe, and has been found to reduce alcohol consumption
among schizophrenia patients in a randomized-controlled
trial (referring to the study conducted by Petrakis
(Psychopharmacology; March 2004; 172(3):291-297)).
MORE RESEARCH NEEDED
Though there have been recent reports of successful treat-
ment of alcohol dependence in schizophrenia patients using
acamprosate, much more research is needed. Other promis-
ing medications, particularly topiramate, have not been
investigated yet in this patient population and currently only
case reports showing its efficacy in schizophrenia patients
with alcohol dependence are available.
The bottom line is that conventional drugs for treating alco-
hol dependence are probably effective in schizophrenia patients
as well, though more evidence is needed in order to guide clini-
cal decision making. Regarding antipsychotic medications, cloza-
pine and long-acting antipsychotics seem to be particularly effec-
tive. Finally, though effective treatment of schizophrenia symp-
toms is necessary to improve alcohol use outcomes, it may not
be enough; targeting the alcohol use disorder with proper med-
ications can have significant effects on outcomes.
Read more on alcohol addiction in
schizophrenia at http://ow.ly/66YXL
August 2011 n9
most
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said
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United Kingdom Cognitive behavioural
therapy may be no more efficacious
than other simpler strategies, accord-
ing to the Cochrane Database of
Systemic Reviews (April 13, 2011).
Trial-based evidence suggests no
clear and convincing advantage for
cognitive behavioural therapy over
other and sometime much less sophis-
ticated therapies for people with schiz-
ophrenia, wrote the authors.
Compared to other psychotherapies,
there was no difference in outcome in
terms of relevant adverse events, nor
in relapse rates over any time period,
or rehospitalization. Various global
mental state measures failed to show
difference (4 RCTs, n=244, RR no
important change in mental state 0.84
CI 0.64 to 1.09). More specific meas-
ures of mental state failed to show dif-
ferential effects on positive or negative
symptoms of schizophrenia but there
may be some longer term effect for
affective symptoms (2 RCTs, n=105,
MD BDI -6.21 CI -10.81 to -1.61).
Read more at
http://ow.ly/51Xzs
China The reliability of the Symbol Digit
Modalities Test (SDMT) and the Digit
Vigilance Test (DVT) was clarified in
the Archive of Clinical Neuro-
psychology (August 2011; 26(5):405-
411). The SDMT and DVT are reliable
for a group of subjects but limited for
individual subjects with schizophrenia
in 1-week interval clinical trials, wrote
the authors. The study was conducted
on 147 participants with schizophrenia.
Each subject had both tests adminis-
tered twice at one week intervals.
Test-retest reliability was determined
through the calculation of the intra-
class correlation coefficient (ICC),
wrote the authors, who also used the
Bland-Altman analy-
sis which included a
scatter plot of the dif-
ferences between test
and retest against their
mean. Using a paired t-test,
researchers evaluated system bias.
The ICC for the SDMT was 0.87 and
that for the DVT was 0.83, wrote the
authors. The mean difference scores
of the SDMT and DVT were 1.5 (4.7%
of the first session mean; p= .002) and
-46.4 (7.6% of the first session mean;
p< .001). The ICCs show both tests to
be stable measures but the paired t-
test indicates a practice effect, and the
LOAs show large variations. Thus, the
SDMT and DVT are reliable for a group
of subjects but limited for individual
subjects with schizophrenia in 1-week
interval clinical trials.
Read more at
http://ow.ly/671eD
Wo r l d B r i e f s i n S c h i z o p h r e n i a
n Magnetic pulses are being tested in
schizophrenia patients to determine
whether they have an effect on audi-
tory hallucinations. Suitable candi-
dates must have auditory hallucina-
tions more than five times a day,
have been on antipsychotic medica-
tion including one atypical medica-
tion for six weeks or longer, and
have been on stable medication for
four weeks prior to the start of the
study. Candidates may not have
either a personal or family history of
seizure disorder in first degree rela-
tives, nor may they have had recent
head injury, acute suicidality, sub-
stance abuse, an implanted pace-
maker or metal in the head or neck.
Patients may not be pregnant.
Contact: St. Josephs Healthcare,
Rose Marie Mueller, RN 905- 522-
1155 ext 36629
More info including full
eligibility critieria is available
at http://ow.ly/4YG82
n Patients with metabolic syndrome are
being recruited for a one year trial of
oral ziprasidone. The purpose of the
study is determine ziprasidones
effect on the distribution of risk fac-
tors associated with metabolic
sydrome in patients presenting with
gulcose intolerance, dylipidema
and/or elevated waist circumference
associated with their current antipsy-
chotic medication. Patients are
excluded if they have a history of
treatment resistance, contraindica-
tions to the use of ziprasidone
according to Canadian prescribing
information, or have a medical con-
dition. Eligible patients also must
also have a minimum of 40 BMI at
baseline. Contact: Pfizer CT.gov Call
Center, 1-800-718-1021
at http://ow.ly/4YG61
n Cognitive remediation is being tested
in a randomized trial to see whether
it is more effective when compared
with a social and functional compo-
nent. There will be three arms. One
arm is experimental cognitive reme-
diation, another with functional
adaptive skills training with
social skills group treatment.
The third arm will include
combined cognitive remediation and
functional adaptive skills training.
Contact: Queens University,
Christopher R. Bowie, 613-533-
3347, christopher.bowie@queen-
su.ca
at http://ow.ly/60b0L
Treating alcohol use disorders in schizophrenia
n Pharmacological interventions identified at Ontario Psychiatric Association meeting
Dr. Shaul Lev-Ran Dr. Shaul Lev-Ran
while those with severe or class II
obesity (BMI 35-39.9) had a 200% increased odds, and those
with morbid or class III obesity (BMI =40) had a 275%
increased odds of migraine.
These findings are interesting because it suggests that
people who have migraines have greater risk of gaining weight
than women who dont have migraines and that the risk of
migraine increases with increasing weight gain, she said.
So its possible that migraine contributes to weight gain or that
weight gain contributes to migraine, but more data is needed.
Further research is needed to determine if migraine can
contribute to causing obesity and/or if
obesity contributes to causing
migraine, she said. It is possible both
disorders share common pathophysio-
logical abnormalities.
To address obesity in people who
have migraine, Dr. Peterlin noted that
evidence suggests lack of exercise may
be one trigger of migraine headaches,
citing an article published in Cephalalgia
(April 2007; 27(4):304-314) by Dr.
Wober and colleagues.
Dr. Wobers study demonstrated that the lack of physical
activity was associated with a 21% increased risk of headache
attacks in adult migraineurs and a 50% increased risk of
migraine in adolescents. In addition, limited data suggest aerobic
activity may reduce headache frequency in episodic migraineurs.
Further evidence suggesting a relationship between obesi-
ty and episodic migraine keeps popping up. A recent study
published in the journal Neurology (Mar. 29, 2011; 76(13):1135-
1138), found that when a group of 24 severely obese patients
with infrequent episodic migraine underwent bariatric bypass
surgery, their headache frequency was significantly reduced.
Specifically, following surgery, migraineurs went from about 4
headaches per month to about 2 headache days per month.
The odds of experiencing a 50% reduction in headache
days was related to greater [mean percent excess weight loss],
independent of surgery type (p<0.05), wrote the authors.
Reductions in severity were also observed (p<0.05) and the
number of patients reporting moderate to severe disability
decreased from 12 (50.0%) before surgery to three (12.5%)
after surgery (p<0.01).
Research presented at the American Society for Metabolic
and Bariatric Surgerys 28th Annual Meeting in Orlando, Fla. in
June provides additional supporting evidence.
In the research, 81 morbidly obese patients with migraines
underwent gastric bypass surgery, and lost 55% of their excess
weight on average. In all, 89% of the patients experienced report-
ed significant improvement in migraine headaches, while 57 of 81
reported complete resolution. Nine per cent reported no change.
Research lead by Dr. Peterlin suggests the possibility that
proteins produced by
fat itself could be a
contributing mecha-
nism for developing
migraine.
Adipose tissue is a
dynamic neuroen-
docrine organ that
participates in multiple
physiological and
pathological processes
including inflammation. A manuscript by Dr. Peterlin sug-
gests it is associated with migraine.
Clinical, population-based, translational, and basic science
research show multiple areas of overlap between the central and
peripheral pathways regulating feeding and migraine pathophysi-
ology. The current epidemiological research suggests that chron-
ic daily headache prevalence is increased in adults with obesity
and that the prevalence of episodic headaches may be increased
in reproductive aged adults with obesity as well, she wrote in the
manuscript published in Headache (April 2010; 50(4):631-648).
In addition to the epidemiological associations, basic and
translational research has suggested that several proteins and neu-
rotransmitters, which modulate the pathways regulating feeding
and energy homeostasis, may also play a role in migraine patho-
physiology, including serotonin, orexin, and adipocytokines.
To be certain of this association, Dr. Peterlin said it would
be necessary to conduct a longitudinal study on people who do
not have headaches and are obese at baseline to determine
whether obesity causes
Link between migraine and obesity unclear, say specialists
#Obesity and migraine
headaches are related,"
said Dr. Lee Peterlin, an
assistant professor at
Johns Hopkins University
School of Medicine.
10 nAugust 2011
Dr. Lee Peterlin
Spain Risk factors that may cause a patient to drop out
of preventive treatment for migraines include the
drug used as preventive treatment, side effects, a
younger age of the patient and a lower number of
seizures, according to a study published in Revista
de Neurologia (August 16, 2011; 53(4):201-208).
The researchers conducted a prospective study of
patients who had migraines requiring preventive
treatment. They were treated with one of the top
three drugs including nadolol; a beta blocker, topira-
mate; a neuromodulator, and flunarizine; a calcium
antagonist. Of 800 patients with migraine who
required preventive treatment for the first time, the
drop-out rate was 19.7%. In the drop-out group, the
variables age, number of seizures, number of
seizures prior to preventive treatment and side
effects showed significant differences with those
from the group of patients who did not drop out of
preventive treatment, the authors wrote. Preventive
measures for migraines have a drop out rate of 30%.
Read more
at http://ow.ly/671mk
China Women using triptans or ergots during pregnan-
cy were found to have low risk for adverse events in
delivery outcome, according to a study in Drug
Safety (August 2011; 34(8):691-703), though data
on triptans other than sumatriptan is lacking. The
register study was conducted. Exposure to migraine
medication was determined from interviews con-
ducted by the attending midwife
and medical records in antenatal
care (1995-2008) and partly by link-
age to the Prescribed Drug Register (2005-2008).
Use of ergots or triptans during early pregnancy
(first trimester) occurred in 3,286 women with 3,327
infants, while use after the first trimester occurred in
1,394 women with 1,419 infants, wrote the authors.
Women using drugs for migraine had not previous-
ly had more miscarriages than expected. Women
that were using such drugs for migraine were older,
had no previous infants, and more often had a high
body mass index.
Read more
at http://ow.ly/671pl
Wo r l d B r i e f s i n Mi g r a i n e
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by Louise Gagnon, Correspondent, The Chronicle
S
URGICAL INTERVENTION CAN treat migraine in patients
who do not respond to standard therapies, according to
research presented at the annual meeting of the
American Society of Aesthetic and Plastic Surgery in Toronto.
We had a high success rate
at five-year follow up, said Dr.
Bahman Guyuron, the chair of
the department of plastic sur-
gery at Case Western
University in Cleveland.
A study of 125 patients ran-
domized 100 patients to surgi-
cal deactivation of migraine
headache trigger sites while 25
patients served as control subjects. This ratio was used in accor-
dance with the studys biostatistician using the envelope technique
to determine the size of the control group and the intervention
group (Plast Reconstr Surg Feb. 2011; 127(2):603-608).
Of 100 patients, 89 underwent surgical deactivation of
migraine trigger sites, and 79 were followed for five years. Of
the 79 patients, Dr. Guyuron noted that 10 patients underwent
deactivation of additional trigger sites, and were not included
in the five-year analysis, leaving 69 patients for analysis.
A total of 20 patients experienced complete elimination of
their migraines, 41 patients experienced a significant decline
in the frequency and severity of their migraines (at least 50%
reduction), and eight patients had no significant change,
defined as less than 50% improvement.
When compared with the baseline values, all measured
variables at 60 months improved significantly (p<0.0001),
wrote the authors of the article in Plastic & Reconstructive
Surgery. The results of this five-year analysis were not com-
pared with the control group who were only followed for one
year. Based on the design of the initial study, most patients in
the control group underwent surgical treatment at one year.
There have been advances in the medical management of
patients with migraine, but there continue to be patients who
do not respond to medical management or who do not toler-
ate the side effects of standard pharmacotherapies. In the
U.S., for instance, it is estimated 30 million patients with
migraine are not aided by standard management.
The typical medications that are used to treat migraines
are triptans, said Dr. Guyuron. But these medications have
side effects and not every patient can tolerate them.
SURGERY AN OPTION
Surgery is a good option for patients with migraines who fail
to respond to medical management, noted Dr. Guyuron, cit-
ing a study he co-authored that was published in Plastic &
Reconstructive Surgery (Jan. 2005; 115(1):1-9), which found that
surgical deactivation of migraine trigger sites can eliminate
or significantly reduce migraine symptoms.
The motivation to explore the impact of surgical intervention
came when he noticed that patients who had undergone fore-
head rejuvenation as a cosmetic procedure also enjoyed the ancil-
lary benefit of a decrease in headaches or migraines.
The idea for surgical treat-
ment started when I reviewed
results from a retrospective
study of patients who had
forehead lifts and reported that
their headaches went away after
the esthetic procedure, he
said. This led to a pilot
prospective study to see the
impact on treating migraines.
FACTORS LEADING TO A MORE POSITIVE OUTCOME
In further investigation, Dr. Guyuron has found that a higher
rate of use of over-the-counter medications, a higher rate of
head and neck injury, and older age increase the chances of a
successful surgical intervention.
By contrast, he said, patients who have had a younger age
of onset of migraines are less likely to benefit from surgical
treatment for migraines.
If the headaches are occurring when they are younger, [it
is] more likely the migraines are being triggered from the nose
and from the septum, he said, citing the 2005 article in Plastic
& Reconstructive Surgery. The chance of success for those who
have nose-related migraine headaches is slightly less than those
who have migraines triggered from other sites.
SOME TRIGGER SITES MORE RESPONSIVE
Other sites that are more usually responsible to elicit migraines
are the frontal, temporal, and occipital sites. Dr. Guyuron
removes the corrugator supercilii muscles in the forehead to
address the frontal migraine trigger, and where patients have
occipital migraine headaches, he removes a small piece of mus-
cle encasing the nerve and replaces it with a soft tissue flap.
Dr. Guyuron said his experience to date has shown that he
needs to be more surgically aggressive in treating patients
whose trigger sites lie in the nose.
Botulinum toxin type A has been applied as a therapy to
treat migraine headaches, noted Dr. Guyuron, and was
approved for the indication in Canada in 2011.
It paralyzes the muscles, he said, noting Botox can also be
used for other purposes, such as identification of trigger sites.
Botox can be used to confirm the trigger sites, he said. We
have also put together a constellation of symptoms that repre-
sent specific trigger sites.
Some trigger sites include frontal, temporal, and occipital sites.
In another study of 75 patients
Surgical intervention and migraine treatment
n Shows promise in patients who do not respond to traditional therapies, says plastic surgeon
n A clinical trial is being conducted to
evaluate whether the frequency of
migraine headaches can be con-
trolled in migraineurs with aura and
a patent foramen ovale. Patent fora-
men ovale is a slit-like opening
between the right and left atria which
normally close at or soon after birth.
Patients are randomized to have the
ovale closed, or to continue with
standard medical treatment. Primary
outcome measures include
headache frequency before and
after ovale closure, secondary out-
come measures include acute
migraine medication use, quality of
life evaluations, the effects of anti-
thrombotic medication, adverse
events, and patent foramen ovale
closure. Patients must be between
18 and 65, have migraine
headaches with aura diagnosed by a
physician, who have not responded
to or cannot take migraine preventa-
tive medications. Patients are
excluded if they have a clinical histo-
ry of stroke, if they cannot take ASA
or clopidogrel, or if they are pregnant
or wish to become pregnant within
the next year. Contact: Contact:
PRIMA Trial Staff
info@primatrial.com
Full study criteria including
trial locations is available at
http://ow.ly/5Nzwz
n Intravenous fluid hydration is being
studied to determine whether it may
be used to reduce headache pain in
emergency room pediatrics. The
investigators propose a study to
examine the response to intra-
venous fluid hydration as initial ther-
apy comparing a group with expec-
tation of medication and another
group without the initial expectation
of medication, wrote the authors.
The intervention is 0.9% saline
administered over a period of 30
minutes, with primary outcome
measures being the nine faces pain
scale, the visual analogue scale,
and four categories (none, mild,
moderate, or severe). Secondary
outcomes are nausea and/or vomit-
ing within 30 minutes, headache
recurrence or worsening within 24
hours after leaving the emergency
department, or returning to the
emergency department. Patients
must be between five and 17 years
of age. Contact: Stollery Childrens
Hospital Emergency Department,
Edmonton, Lawrence P Richer, MD,
MSc 780-407-7329 lricher@ualber-
ta.ca
Full study criteria including
trial locations is available at
http://ow.ly/5NBvG
ALMOST HALF OF all adults have headache
disorders such as migraine and tension
headache resulting in an economic burden,
according to the World Health Organization.
Migraine alone is the cause of an esti-
mated 400,000 lost days from work or school
every year per million of the population in
developed countries, and in the EU, the total
annual cost of all headache has recently
been estimated at 155 billion euros ($219 bil-
lion), reports Reuters (May 4, 2011).
"The financial costs to society through
lost productivity are enormous," wrote the
authors of this study.
Headache and migraine disorders are
greatly underrated and underreported by
health systems and receive too little atten-
tion, said Dr. Shekhar Saxena, the World
Health Organization's director of mental
health and substance abuse disorders,
said in a press release.
Headaches can be debilitating for
many people, rendering them unable to
work. During migraine attacks, 90 per cent
of people postpone household chores,
almost three-quarters have limited ability to
work and half of them miss work entirely.
The study also found that 47% of adults
have a headache disorder, and that
headaches are under-recognized, under-
diagnosed, and under-treated.
Read this study online at
http://ow.ly/671ss
Headache disorders are economic burden, says WHO
Dr. Bahman Dr. Bahman
Guyuron Guyuron
# The typical medications that
are used to treat migraines are
triptans," said Dr. Guyuron.
#But these medications have
side effects and not every
patient can tolerate them."
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A
N EFFECTIVE MEASURE to assist in diagnosis of parkin-
sonian syndromes in clinically uncertain cases is
123
I-
ioflupane, according to research presented at the annual
American Academy of Neurology
meeting in Honolulu, Hawaii.
The research found that of the
patients who had a management plan
when they started the study, signifi-
cantly more patients who had taken
123
I-ioflupane had management plan
changes in 12 weeks, compared to
the control group (p=0.004).
In the imaging and control group,
the movement disorder specialist
would see them at four weeks, and 12 weeks, said Dr. Frederick
Weiland, Sutter Medical Group Diagnostic Medical Imaging co-
director of nuclear medicine in Sacramento, Calif. and co-author
of this presentation. There was management plan change in 49
per cent of patients over 12 weeks if they had [
123
I-ioflupane ]
and 31 per cent if they did not have the [
123
I-ioflupane] results.
He said this diagnostic tool could lead to a quicker and more
accurate diagnosis in patients with a clinically uncertain parkin-
sonian syndrome (44% in the imaging group vs. 12% in the
control group had changes in diagnosis at 12 weeks, p<0.001),
and that could bring more appropriate treatment faster.
[
123
I-ioflupane] provides objective versus subjective evidence.
Early evaluations can lead to misdiagnosis even in the best of
hands, he said, citing a study in Movement Disorders (Oct. 2004;
19(10):1175-1182) that found that confidence in a diagnosis of
presynaptic parkinsonian syndromes was increased from 58.4
22.2% at baseline to 88.4 14.1% when
123
I-ioflupane was used.
Recently, we tested 20 patients that were referred by move-
ment disorder specialists because they had suspected
Parkinsons disease (PD) and 12 patients had normal scans.
This means that only eight patients had abnormal scan results
suggesting PD. The neurologists that I work with tend to treat
patients with negative scans very conservatively and will typi-
cally stay away from prescribing PD drugs.
He said in cases where the diagnosis is unclear and the
123
I-
ioflupane radiological examination is unavailable, the only way to
be sure patient has Parkinsons disease is to treat them, and see
if they improve. The sensitivity of this procedure is between 95
and 97%, while the specificity is between 93 and 100%.
He also said that
123
I-ioflupane shows the loss of dopamine
transporters that are the hallmark of
Parkinsons disease, permitting a diagnosis to
be confirmed more quickly. By virtue of
what it is, [
123
I-ioflupane] is a very elegant
indicator of the loss of functional striatal
dopaminergic neuron terminals in patients
with degenerative forms of parkinsonian syn-
drome he said. You have to have 60 to 80
per cent loss of nigro-striatal dopaminergic
neuron function before symptoms manifest
themselves, citing an article in the Journal of
Neurology (2006; 253:IV/2-IV/7).
He says that in this procedure significant loss of these trans-
porters is easily visible to a trained nuclear medicine physician.
CONTROVERSY
News that U.S. FDA approved
123
I-ioflupane for this purpose was
accompanied by criticism from Dr. William Weiner, director of the
Maryland Parkinsons Disease and Movement Disorders Center.
In a Neurology Today article, Dr. Weiner was quoted as saying
quite honestly, we expect medical students to be able to dif-
ferentiate between essential tremor and parkinsonism.
In an interview with THE CHRONICLE, Dr. Anthony Lang,
director of the Morton and Gloria Shulman Movement Disorders
Centre in Toronto and officer of the Order of Canada, said Dr.
Weiners comments should be taken with a grain of salt.
There is some validity in his opinion, he said, but [...]while
hopefully most medical students can differentiate between garden
variety essential tremor and garden variety Parkinsons disease, we
still commonly see errors in diagnosis in both directions.
Though this diagnostic adjunct is not yet available in
Canada, Dr. Lang said he was optimistic about its growing use.
I think that this tool would be very useful. In fact I would
use it in my own practice periodically, he said. One would
not like to see this tool used to the exclusion of actually think-
ing about the problem clinically.
Read more on
123
I-ioflupane at http://ow.ly/5Uvhi
Radiological test shows promise as diagnostic adjunct
n Results presented at the annual American Academy of Neurology meeting in Hawaii
C l i n i c a l T r i a l
n ELND002 is being tested for safety and
tolerability in patients with multiple
sclerosis, with the possibility that it
may reduce clinical relapses. The
12-week study requires patients
between the ages of 18 and 65, who
have a documented medical history
of relapse in the last year, an inade-
quate response or intolerability to
interferon and/or glatiramer acetate,
and who are able to undergo GD
administration and repeat MRI test-
ing. Patients are excluded if they
have primary progressive MS, a his-
tory of treatment with recombinant
humanized monoclonal antibodies,
have received treatment with
immunosuppressant medications or
any component of the investigational
drug, a medical history that would
impact outcome, or any other clini-
cally significant abnormality that
would affect physical, neurological,
laboratory, or ECG examination.
Contact: Elan Pharmaceuticals,
Lacey Powers, 469-916-8641, lpow-
ers@dandersoncompany.com
More information on this
clinical trial at http://ow.ly/4YFe5
12 nAugust 2011
Wo r l d B r i e f s i n Mo v e me n t D i s o r d e r s
USA Functional loss occurs at different points
in the progress of Parkinsons disease
which can be used to monitor the status
of patients, says a study in Physical
Therapy (July 21, 2011). In the study, 339
patients had their disease severity evalu-
ated using the Unified Parkinsons
Disease Rating Scale motor score. The
mean score for the sample was 39.2
(SD=12.93). At each stage of PD (from
least to most involved), scores on func-
tional measures indicated a significant
and progressively reduced functional sta-
tus, wrote the authors. They noted that
limitations began early in the disease
from measurements for functional capac-
ity using the Continuous Scale Physical
Functional Performance Test, and with
functional axial rotation. Both of these
measures were found to mark consistent
loss of performance throughout all stages
of the disease.
More info at http://ow.ly/670Pe
United Kingdom Impulse control disorders
were associated with Tourette syndrome
in a study published in the Journal of the
Neurological Sciences (July 6, 2011).
The study included 31 patients with a
Tourette syndrome diagnosis who were
screened for impulse control disorders
using the Minnesota Impulse Disorders
Interview. The Health Related Quality of
Life was assessed using
the Medical Outcomes
Study 36-Item Short-Form
Health Survey and the Gilles de la
Tourette Syndrome Quality of Life Scale.
Twenty-three out of 31 participants
(74.2%) had at least one ICD. The most
common ICDs were intermittent explo-
sive disorder (51.6%) and compulsive
buying disorder (41.9%), wrote the
authors, who also noted that the number
of impulse control disorders significantly
correlated with a reduced health related
quality of life (p=0.011) as measured by
the Gilles de la Tourette Syndrome
Quality of Life Scale.
More info at http://ow.ly/670QT
Dr. Frederick Dr. Frederick
Weiland Weiland
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Dr. Anthony Lang
by Kristina Fiore, Special to The Chronicle
P
ATIENTS WHO ABUSE methamphetamine and other related
stimulants may be increasing their chances of developing
Parkinsons disease, researchers have found.
Those hospitalized in California for
methamphetamine or other ampheta-
mine-related conditions had a significant-
ly greater risk of developing the neurolog-
ical condition than those admitted for
appendicitis or cocaine use, Dr. Russell
Callaghan, of the University of Toronto,
and colleagues reported online in Drug and
Alcohol Dependence.
The findings support the long-
hypothesized notion, based on animal
data, that meth/amphetamine exposure might lead to enduring
damage of brain dopamine neurons in humans, they wrote.
Research has shown that methamphetamine and other
amphetamine-type stimulants can damage dopaminergic neu-
rons, and scientists have long suspected that the drugs can pre-
dispose users to Parkinsons disease, a dopamine-deficiency dis-
order. Recently, Kaiser Permanente researchers found in an
observational study that amphetamine sulfate and dextroam-
phetamine sulfate abuse can increase the risk of the disease.
So Dr. Callaghan and colleagues conducted a retrospective
cohort study using all linked statewide California inpatient hos-
pital episodes and death records via the California Patient
Discharge Database and Vital Statistics Database from Jan. 1,
1990 through Dec. 31, 2005.
They compared the 40,472 patients admitted for ampheta-
mine-related conditions with the 207,831 patients admitted for
appendicitis and with the 35,335 admitted for cocaine-use disor-
ders. Patients were at least 30 years old and were followed for up
to 16 years. The researchers found that the amphetamine cohort
had a greater risk of Parkinsons than either control group.
They had a 76% increased risk of developing the disease
compared with the appendicitis patients (95% CI 1.12 to 2.76,
p=0.014) and almost a 2.5-fold greater risk than cocaine users
(HR 2.41, 95% CI 1.32 to 4.41, p=0.004).
They noted that the cocaine cohort didnt have a significantly
increased risk of disease compared with the appendicitis patients.
Cocaine and amphetamines are both dopaminergic stimu-
lants, the researchers explained, but they have a different pri-
mary mechanism of action. Cocaine is active in monoamine
neurotransmitter transporter blockade, while methampheta-
mine is active in monoamine neurotransmitter release and
transporter blockade. The findings coincide with animal mod-
els that havent shown dopamine neuron toxicity after expo-
sure to cocaine.
Dr. Callaghan and colleagues wrote that the work extends
an earlier study they performed, by including a longer follow-
up time, a younger and larger sample, and linked mortality
information. They also noted that their study was subject to
the usual limitations of a retrospective study relying on admin-
istrative diagnostic codes.
The investigators cautioned that the findings likely only pertain
to high-dose meth/amphetamine users, as 96% of patients in that
cohort were diagnosed with abuse or dependence at admission.
While our study does raise the question of whether licit
amphetamines might also increase the risk of Parkinsons dis-
ease, they wrote, it is important to emphasize that our find-
ings might not at all relate to those individuals who take much
lower doses of amphetamine drugs for therapeutic purposes.
Copyright Med Page Today, LLC. All rights reserved. Reprinted with
permission. www..medpagetoday.com
Stimulants increase likelihood of developing Parkinsons
n Hypothesis linking stimulant usage and Parkinsons confirmed in University of Toronto study
(Clostridium Botulinum Neurotoxin Type A [150 kD],
free from complexing proteins)
XEOMIN
is indicated for blepharospasm, cervical dystonia of a predominantly rotational form (spasmodic torticollis) and post-stroke spasticity of the upper limb.
Merz Pharma Canada Ltd. wishes to inform physicians of the This new program is designed to make it easier for
patients in need of XEOMIN
by paying up to 20% of the

total prescription costs.
For more information contact your Merz Pharma Canada
representative, call us at 1-866-RxHelp4 (1-866-794-3574)
or go to www.iTrialRx.com
Advantage Program
XEOMIN
Patient Assistance Plan

N
ew
L a y p r e s s
nLewy body dementia is discussed by a
physician who has the condition him-
self. Dr. Geoff Kalchman, a retired
physician in Toronto, talks about his
experiences with the condition that
led to him having several car acci-
dents. His wife discusses how a lack
of facial expression symptomatic of
the condition caused her some dis-
turbance over the years that the con-
dition progressed undiagnosed and
unrecognized.
Watch the CTV news item at
http://ow.ly/4WvbH
nClinics outside of Canada are capitaliz-
ing on impatient patients who want
CCSVI treatment immediately,
reports the Globe and Mail (May, 10,
2011). Patients are paying upwards
of tens of thousands of dollars to
recieve the treatment in the U.S.,
Costa Rica and Bulgaria, for what
would cost around $6,300 in Ontario.
The fact that patients are being
charged for a procedure that is not
yet validated, that it involves serious
risks and that there isnt systematic
collection of information about the
safety and efficacy raises major red
flags, said Jonathan Kimmelman,
associate professor of biomedical
ethics at McGill University in the
newspaper article.
Read this Globe and Mail
article at http://ow.ly/5WmBJ
n Using small-angle neutron scattering
equipment at the laboratorys high
flux isotope reactor, researchers at
the Oak Ridge National Laboratory
and the University of Tennessee.
have identified the earliest aggre-
gate species of the protein that are
believed to be the most toxic,
Science Daily reports, (May 19,
2011). Researchers say the next step
is to take drug molecules and see
how they can interact and affect
these structures in the hope that a
drug could prevent neurdegeneration
associated with Huntingtons dis-
ease.
Read this article at
http://ow.ly/5WmFy
d see
en 95
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HALF OF MULTIPLE SCLEROSIS patients on dis-
ease modifying drugs (DMD) cease adher-
ence after two years, suggests a study in
the Canadian Journal of Neurological
Sciences (May 2011; 38(3):429-433).
Adherence to [disease-modifying
drugs] in adult MS patients in Ontario is
poor, which is consistent with previously
reported adherence rates to MS [disease-
modifying drugs] in other regions. No sig-
nificant differences in adherence exist
between the DMD evaluated in this study,
wrote the authors.
The study looked at four different inter-
feron-based drugs included in this study:
intramuscular interferon beta-1a (i.m.
IFN-1a, Avonex), subcutaneous interfer-
on beta-1a (s.c. IFN-1a, Rebif), subcuta-
neous interferon beta-1b (IFN-1b,
Betaseron) and glatiramer acetate
(Copaxone).
The data was collected from an Ontario
drug-coverage database which identified
682 people newly prescribed multiple scle-
rosis medications. The researchers fol-
lowed their progress from April 2006 until
March 2008.
Cumulative persistence rates were
analysed by the Kaplan-Meier method.
The proportion of patients reaching the
study endpoints after the two year follow-
up period was also calculated, wrote the
authors of the study.
Though 56% had stopped their medica-
tion after two years, this finding marked a
trend in nonadherence that started after
six months.
Cumulative persistence rates for all
four [disease-modifying drugs] were similar
over time (p=0.80), ranging from 73.6-
79.1% at six months, 59.1-63.1% at one
year and 41.5-47.4% at two years. After
two years, the proportion of patients who
had discontinued treatment, switched to
another DMD or died was similar among
DMDs (p=0.79, Fishers exact test).
Switching between [disease-modifying
drug] types was low and occurred in 3.4-
6.5% of new DMD users.
Read this study online at
http://ow.ly/670SU
Adherence to MS meds less than half after 2 years
Dr. Russel
Callaghan
by Jo
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by Louise Gagnon, Correspondent, The Chronicle
H
YPOMANIA IS AN effective response to combat depres-
sive episodes that occur in bipolar depression, and
does not need to be treated,
according to a Toronto psychiatrist in
private practice.
It is a short-term effective treatment
that helps people deal with depressive
states, said Dr. Brad Bowins in an inter-
view with THE CHRONICLE OF
NEUROLOGY & PSYCHIATRY.
Most clinicians miss hypomania
because they rely on the definition of
hypomania as outlined in the fourth edi-
tion of the Diagnostic and Statistical Manual of Mental
Disorder (DSM-IV), which states it has to be present for at
least four days, noted Dr. Bowins.
If people are going by the manual, they are missing the
majority of what is out there, said Dr. Bowins. It is very often
out there if you look for it. It can take place for a few hours to
three days. It is more of a spectrum than a discreet entity.
HYPOMANIA USUALLY ACCOMPANIES DEPRESSION
When hypomania is activated in one to three days, depressive
symptoms are not usually eliminated altogether, according to
several studies in the literature. Research indicates that hypo-
mania is as prevalent as depression, and mania is far less com-
mon, said Dr. Bowins. What is usually present is a mixture of
hypomanic and depressive symptoms.
When depression co-exists with hypomania, there can be
extraordinary periods of functioning for individuals in which
they rebound from their distressing periods.
Depressive inhibitions impair motivation, physical behav-
iour, and cognition, said Dr. Bowins. In addition, depressive
inhibitions engender social avoidance.
Depressive inhibitions are very much linked to social inhi-
bitions or social anxiety, said Dr. Bowins. When individuals
are depressed, there is usually reduced social extroversion.
When there is less social inhibition, there is better social func-
tioning and greater social extroversion.
Hypomania, however, can act as a defense mechanism
which overrides depressive inhibition. Given it has that ability,
clinicians should encourage their patients who report that they
are depressed to engage in more mental and physical activity as
ways of coping with their depression, said Dr. Bowins.
It is worthwhile to try to engage patients in social activity,
but not in an overwhelming sense, said Dr. Bowins.
Studies show that the
worse an individual is at
baseline in terms of
their depressive state,
the more that the indi-
vidual can benefit from
hypomania, said Dr.
Bowins. The lower the
functioning of the indi-
vidual to begin with, the
higher the impact that
hypomania will have, he said.
PHARMACOTHERAPY MAY NOT BE NECESSARY
In one small study, monoamine oxidase inhibitors induced
hypomania, and optimal social adaptation, and optimal adapta-
tion was achieved in about half of the patients.
Pharmacotherapy is not necessary to induce hypomania in
patients, noted Dr. Bowins.
Clinicians do not need fear induction of hypomania in an
individual with depression. The vast majority do not go into
a manic state, he said, adding that many of those who experi-
ence manic episodes also have hypomanic episodes that do not
progress to mania. There is a tremendous upside and limited
downside to get people [who are depressed] into a hypomanic
state.
If an individual has a predisposition to mania, it would be
wise to prescribe a mood stabilizer as well as an antidepressant,
said Dr. Bowins.
Contemporary culture values hyperthymic personalities,
where individuals are perpetually in a hypomanic state, are
highly productive, engaging, and are tireless, notes Dr. Bowins.
About one per cent of the population is this type of per-
sonality, but there is an increasing frequency, he said. In
todays society, to be on is a good thing. Many people are
drinking coffee and other stimulating drinks like Red Bull,
pushing themselves to adopt a hyperthymic personality.
Read Dr. Brad Bowins special review article in the Journal
of Affective Disorders at http://ow.ly/5W7jT
Hypomania could be the bodys way to combat depression
n Private practitioner says psychiatrists shouldnt rely on DSM-IV to diagnose hypomania
#Studies show that the
worse an individual is at
baseline in terms of their
depressive state, the more
that the individual can
benefit from hypomania,"
said Dr. Bowins.
n Oral OPC-34712 will be tested as an adjunctive therapy in adults with major
depressive disorder. The non-randomized study will attempt to measure the safe-
ty and tolerability of the drug by examining frequency and severity of adverse
events. It will also determine the change from baseline in the Sheehan Disability
Scale, the Inventory of Depressive Symptomatology, and the Clinical Global
ImpressionSeverity of Illness scales. Patients must be between 18 and 65
years of age to qualify. The study will begin in October 2011. Contact: Susan
Honn, 512-579-4714, shonn@incresearch.com.
Full study criteria available
at http://ow.ly/5T7Sv
n Mindfulness-based cognitive therapy (MBCT) and its contribution to combating depres-
sion in patients with a traumatic brain disorder is being examined at Lakehead
University. Outcome measures include evidence of decreased depression symptoms
as measured by several scales. Secondary outcome measures include improvement
of pain intensity, attention/concentration, satisfaction with life and other psychological
symptoms. There are two arms to the study, a control arm and MBCT. In the non-con-
trolled MBCT arm, subjects participate in weekly one and a half hour group sessions
over a period of 10 weeks. These sessions include exercises such as meditation,
awareness, and breathing techniques, which subjects are encouraged to practice out-
side of the sessions. Contact: Lakehead University, Michel Bdard, PhD, 807-343-
8630 mbedard@lakeheadu.ca Full study criteria available
at http://ow.ly/5TaWb
Dr. Brad Bowins
14 nAugust 2011
August 2011 n15
A
new clinic is opening up to treat the after effects
of intimate partner violence in London, Ont at
the Merrymount Family Support and Crisis
Centre.
Marilyn Ford-Gilboe, PhD, is a registered nurse and
professor at the University of Western Ontario in
London, Ont., and Faculty Scholar and Echo Chair in
Rural Womens Health Research.
She has recently entered into a partnership with
London Middlesex Housing Corporation to open this
clinic.
She says that while the clinic will be open to every-
one, it has been designed to be of particular service to
women who are in various stages of removing them-
selves from a situation where they are experiencing
intimate partner violence.
There are a wide range of issues that are all docu-
mented in research literature [for which] the nurse
practitioner and the rest of the staff who work in this
clinic will be supporting women, she said.
Along with a wide range of physical health symp-
toms that women typically report after intimate part-
ner violence are physical fatigue, anxiety, depression,
and chronic pain.
So there'll be counselling services available for
women with these issues, she said.
PAIN A CONTINUING SYMPTOM
Dr. Norman Buckley is the founder and director of
the Pain Management Centre for Hamilton Health
Sciences and McMaster University. He said that while
he is not a specialist in chronic pain resulting from
domestic violence, he has heard of cases where chron-
ic pain has conicided with psychiatric symptoms fol-
lowing intimate partner violence.
There was one woman who had an anxiety disor-
der that manifested itself in non-specific pain, said
Dr. Buckley, who also said this anxiety began occur-
ring after having her life was put in jeopardy by her
spouse. Another had pain persisting in the scars of
knife wounds. One mode of treatment is to offer
injections of local anesthetic and steroids, he said, but
even though
the treat-
m e n t
reduced the
pain the
p a t i e n t
found that
the process
of injection
consistently
c r e a t e d
flashbacks which elevated her anxiety.
Chronic pain, he said, is a symptom associated with
depression.
FINANCIAL BARRIERS A BARRIER TO TREATMENT
Financial barriers can be an obstacle to women who
are experiencing or have experienced intimate partner
violence, but its not the only one that is at play for
women experiencing intimate partner violence..
Its currently difficult for women without financial
resources to access any kind of psychological coun-
selling, said Dr. Robin Mason, PhD, a psychologist at
the Womens College Research Institute in Toronto.
She has studied domestic violence for 10 years and
has developed an education program to help physi-
cians and other clinicians learn how to work with
patients who may be undergoing intimate partner vio-
lence.
She said the added stress of trying to maintain
themselves financially is one of many barriers to seek-
ing help before and after leaving an abusive relation-
ship.
In addition, she said, many may feel that seeking
medical help suggests a problem exists within them-
selves, and
so they may
avoid treat-
ment alto-
gether.
M a n y
choose not
to see psy-
c h i a t r i s t s
because it
feels like its
medicalizing them, like they have become the problem
in some way, Dr. Mason said.
This may make it difficult for a patient to recognize
they are experiencing the after effects of an abusive
relationship that may require psychiatric assistance.
Dr. Mason also said that while the results of this
study may be useful, physicians should consider that
each case is unique.
Its important to recognize women are also enor-
mously resilient, and not all women have that same
trajectory of experience, she said, adding that this is
particularly true in patients who have quickly removed
themselves from a situation where they may have
experienced intimate partner violence.
Read a recent study by
Dr. Ford-Gilboe at http://ow.ly/673Gf
Treating the long-term effects of intimate partner violence
n Womens health researcher intends for clinic to be accessible to women after intimate partner violence
Identifying suspected intimate partner violence
THERE MAY BE LESS obvious signs a patient
may be experiencing an abusive relation-
ship, said Robin Mason, PhD.
Shes a psychologist who has studied
domestic violence and developed an edu-
cation program to help physicians and
other clinicians learn how to work with
patients who may be undergoing intimate
partner violence.
She said the signs of abuse may vary.
It depends on the kind of abuse in the
relationship, because not all abuse
includes physical abuse. There are also
very abusive relationships with psycho-
logical or emotional abuse.
Emotional or psychological abuse may
be more difficult to diagnose, said Dr.
Mason, and more difficult to recover from.
If you have a physical episode, a
physical assault, its very clear something
has happened. But if someone is eroding
your self-esteem in a very continuous
form, minimizing your experiences,
devaluing your opinion and experiences,
its a slow erosion of the self thats hard to
put your finger on.
She said self doubting, having difficul-
ty identifying feelings, or describing ones
self as incompetent may be red flags. As
well, she said, a patient may be very anx-
ious about her partner finding out that she
is seeking help and thereby exposing the
abuse.
Another sign is substance abuse,
which she said may make people sus-
ceptible to abuse, as well as be a form of
self-medicating to lessen the symptoms
of abuse.
Dr. Mason provided a sample script of
what she might say to a patient who she
suspects may be experiencing intimate
partner violence.
Sometimes when I see this sort of pic-
ture I begin to wonder about whats going
on in this persons life and this persons
relationship so Im going to ask you some
questions about your relationship with
your partner.
She said techniques like these may be
necessary for patients who are reluctant
to recognize a problem with their relation-
ship. Even after a problem is identified,
intimate partner violence can continue.
One reason is that those experiencing
intimate partner violence may remain with
their partner, said Dr. Mason.
It can take a really long time to extri-
cate from these relationships for a whole
host of reasons, she said.
When you add to that the lack of afford-
able housing, whether she has access to
financial means or not, having to take her
kids out of school to relocate, the harass-
ment that can develop as these cases go
through the court system, its not surprising
it takes so long for these women to extri-
cate, she said. Women are being
harassed for a long time on their way out of
a relationship.
Dr. Mason has developed an interac-
tive online video gaming platform to teach
intimate partner violence in many mani-
festations. It currently comprises 17 sep-
arate units, with each divided into three
parts: an interactive didactic section, a
section that uses a simulated patient
avatar, and a quiz.
Its available free, and paid for by the
province of Ontario. And there are CME
credits attached to it, she said.
Read more at www.dveducation.ca
ity as
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n A study led by Dr. Jeffrey Meyer, who
holds a Canada Research Chair in
the Neurochemistry of Major
Depression, may explain the link
between depression and smoking
cessation, e! Science News reports
(Aug. 2, 2011). MAO-A is a chemical
found in cigarettes that helps main-
tain a normal mood. When MAO-A
levels are higher as in early cigarette
withdrawal, it means that this removal
process is overly active, making peo-
ple feel sad, wrote the author.
During active smoking, harman
attaches to MAO-A. During early
withdrawal in heavy smokers who
had 25 or more cigarettes a day,
MAO-A levels rose rapidly to a level
beyond that seen in the healthy com-
parison group. CAMH used the only
PET scanner in the world specifically
dedicated to research in mental
health and addiction to complete this
study.
Read this news report
on addiction and depression
at http://ow.ly/5W9pP
Dr. Norm Buckley Dr. Robin Mason
#Its currently difficult for
women without
financial resources to
access any kind of
psychological counselling,"
said Dr.Robin Mason.
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16 nAugust 2011
co
Speech enabling smartphone app now freely available
which they can download at will,
called the bookshelf tool.
These books are hand-
crafted collections of words
and phrases about specific
subjects, said Levy. Suppose
youre interested in cooking
for example. For the purposes
of chatting with your friends
about recipes, you could
painstakingly add every ingre-
dient that you needed to dis-
cuss, but the bookshelf lets
you do the same thing in sec-
onds.
The phone must have
access to a data plan or wire-
less connection to download a
book, or the customized
vocabulary.
However, already down-
loaded content is accessible
when offline, Levy says.
Alexandra Carling-
Rowland, PhD, is an aphasia researcher at the University of
Toronto who has recently joined this project. She said that she
will examine the effectiveness of MyVoice technology.
When youre living with a severe communication barrier,
you can become very isolated and
you can really begin to lose your con-
fidence, she said. What were going
to do is look at those two areas. Does
MyVoice increase someones com-
munication confidence? Does it help
them participate more in life and
does it help them to become more
independent?
Dr. Carling-Rowland also said this
research would be conducted in col-
laboration with partners from
Sunnybrook Health Sciences, the
Toronto Rehabilitation Institute and
the Aphasia Institute, all located in
Toronto.
The application is currently avail-
able for the iPhone and Android.
Research in Motion recently
announced future versions of the
Blackberry would support Android
applications, and so the application
will work on these phones as well.
More info on this app at http://myvoiceaac.com/
THE NEXT CANADIAN Psychiatric
Association meeting is being held this
October in Vancouver.
This years expert psychiatry series
will be on Emerging Trends in Geriatric
Psychiatry: From Personality Disorders
To Electroconvulsive Therapy, featuring
Drs. Caroline Gosselin and Joel Sadavoy.
Guest speakers include Dr. Anthony
Phillips, the scientific director of CIHRs
institute of neurosciences, Mental
Health and Addiction, who has a presen-
tation called Harnessing a Window of
Opportunity to Transform Mental
Health Research in Canada.
Named for the Canadian Psychiatric
Association founding president, the R.O.
Jones Memorial Lecture will be Setting
the Balance: Energy Metabolism in
Mood Disorders lead by Dr. Trevor
Young, the chair of the University of
Toronto psychiatry department.
Dr. Matthew Hill from the University
of Calgarys psychiatry department will be
presenting Structural Remodelling in
Cortico-Limbic Circuts Following Chronic
Stress Mechanisms and Implications.
Two distinguished member lecturers
include Dr. Gary Chiamowitz from
McMaster University in Hamilton, and
Dr. Harry Karlinsky.
In addition to his work as a clinical
professor in the deptartment of psychia-
try at the University of British
Columbia, Dr. Karlinsky is also an nov-
elist, having written a biography of
Thomas Darwin, the son of Charles
Darwin who in 1879 was involuntarily
admitted to the London Aslym in
Ontario. At the Canadian Psyciatric
Association meeting, hell be moderating
a discussion on the documentary film
Suicide Tourist about people who
travel to Zurich, Switzerland seeking
assisted suicide.
Dr. Chiamowitzs presentation is
called The Criminalization of the
Seriously Mentally Ill: The Need for
Centres of Humility.
This meeting marks the 60th anniver-
sary of the CPA, a milestone that will be
marked by the organizers.
In celebration of this year being the
60th anniversary of the CPA, our open-
ing reception and closing gala will be
extra special. The opening reception will
have a Happy Days are Here Again
theme in our 1950s diner so it is highly
recommended you find those poodle
skirts and letter sweaters and there will
be costume judging, said a letter in the
preliminary program signed by Drs.
Nancy Brager and Glendon Tait, co-
chairs of the organizing committee.
If you have never been to the closing
gala, you will not want to miss this years
B.C. Food and Wine Extravaganza
where Chef Robert Lecrom of Hotel
Vancouver will spoil us with delectable
food and especially chosen wine pairings
for every course, on what will be one of
his final events. This feast will truly befit
our 60th anniversary!
More on the CPA
at http://www.cpa-apc.org
Mi
an
Agenda
Oct. 13-15, 2011
Canadian Psychiatric Associations
Annual Conference
Vancouver
Phone: 613-234-2815
Fax: 613-234-9857
Email: cpa@cpa-apc.org
Oct. 14-16, 2011
ADHD Research into Practice:
A Global View
International conference on
ADHD research and practice
Toronto
Website: www.caddra.ca
Phone: 416-637-8583
Fax: 905-475-3232
Oct. 15-18, 2011
Academy Of Aphasia 49th Annual
Meeting 2011
Montreal
Website: www.academyofaphasia.org
Email: contact@academyofaphasia.org
Phone: 952-920-0484
Oct. 27-29, 2011
6th Canadian Conference on Dementia
Montreal
Website:
canadianconferenceondementia.com
Email: conferences@torontorehab.on.ca
Phone: 416-597-3422, ext. 3693
Fax: 416-597-6202
Oct. 28, 2011
Child and Youth Mental Illness:
Cultural Competency and Pathways
to Reduce Recidivism
Toronto
Email: info@careconferences.com
Website: www.careconferences.com
Phone: 416-444-8455
Fax 416-391-5984
Feb. 1518, 2012
INS - International Neuropsychological
Society Annual Meeting
Montreal
Website: www.the-ins.org/
Phone: 614-263-4200
Fax: 614-263-4366
Let us know about
upcoming conferences
of interest. Contact us at
health@chronicle.org
Canadian Psychiatric Associations annual congress
n The 60th annual conference will be held in Vancouver from Oct. 13 to 15
Aakash
Sahney
Dr. Alexandra
Carling-
Rowland
Alexander
Levy
migraine or vice-versa.
Another way to interpret the
results is that people who are
less obese simply eat less
migraine triggering food, said
Dr. William Pryse-Phillips, a
neurologist and former profes-
sor at the Memorial University
of Newfoundlands faculty of
medicine in St. Johns.
We should point out that
cheese, chicken liver, mono -
sodium glutamate, nitrites of all
kinds in hotdogs, in hamburg-
ers, [...] beer, red wine, and in
some people things like choco-
late, nuts and so on [are] well-
documented precipitants of
migraine headaches-usually
within the next 12 [to] 24 hours
of ingestion in those people
who are susceptible, he said.
He also said that in the
Neurology study, the improved
condition of the migraineurs
could have been a secondary
outcome in patients who
underwent lap-band surgery.
My suspicion is that this is
slightly due to the reduction of
the ingestion of migraine-pre-
cipitating foods as anything
else, said Dr. Pryse-Phillips.
And if theyre eating less, then
theyre eating less of those
foods that can, in some people,
precipitate migraine head aches.
However, Dr. Peterlin noted
that while food choices may
trigger migraines and many
patients do report food triggers,
with the exception of alcohol
and nitrite ingestion, most have
not been well substantiated by
research, including chocolate.
She suggested that patients
can keep a headache and food
journal that tracks what foods
they eat and if they suspect
food could be a trigger to
remove that food. She also said
patients with migraine and obe-
sity should be educated on the
link between these two condi-
tions, and tailor choices of
migraine preventive medica-
tions based on patients obesity
status. Furthermore, she said,
clinicians should promote that
patients maintain healthy
lifestyle choices in both diet
and exercise routines.
More on obesity and
migraine at http://ow.ly/65Orm
THERAPEUTIC CLASSIFICATION Antidepressant/Anxiolytic/Antiobsessional
INDICATIONS AND CLINICAL USE
Adults Cipralex
(escitalopram oxalate) is indicated for the symptomatic relief of Major Depressive Disorder (MDD).
Cipralex
is indicated for the symptomatic relief of anxiety causing clinically significant distress in patients with
Generalized Anxiety Disorder (GAD). Cipralex
is indicated for the symptomatic relief of obsessive-compulsive disorder

(OCD). The obsessions and compulsions must be experienced as intrusive, markedly distressing, time consuming
or interfering significantly with the persons social or occupational functioning. Physicians who elect to use Cipralex
for extended periods should periodically re-evaluate the usefulness of the drug for individual patients.
Geriatrics Although there was no evidence from clinical studies suggesting that use in geriatric populations is
associated with differences in safety and effectiveness, a greater sensitivity of some older individuals to effects of
escitalopram cannot be ruled out (see ADMINISTRATION). Pediatrics Escitalopram is not indicated for use in patients
below the age of 18 (see WARNINGS AND PRECAUTIONS General, Potential Association with Behavioural and
Emotional Changes, Including Self-Harm).
CONTRAINDICATIONS Cipralex
(escitalopram oxalate) is contraindicated in patients with known hypersensitivity

to escitalopram or any of the excipients of the drug product. Monoamine Oxidase Inhibitors (MAOIs) Escitalopram
should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly, at
least 14 days should elapse after discontinuing escitalopram treatment before starting a MAOI. Pimozide Escitalopram
should not be used in combination with the antipsychotic drug pimozide, as results from a controlled study with citalopram
indicate that concomitant use is associated with an increased risk of QTc prolongation compared to pimozide alone.
WARNINGS AND PRECAUTIONS
General
POTENTIAL ASSOCIATION WITH BEHAVIOURAL AND EMOTIONAL CHANGES, INCLUDING
SELF-HARMPediatrics: Placebo-Controlled Clinical Trial Data Recent analyses of placebo-controlled
clinical trial safety databases from SSRIs and other newer antidepressants suggest that use of
these drugs in patients under the age of 18 may be associated with behavioural and emotional
changes, including an increased risk of suicidal ideation and behaviour over that of placebo.
The small denominators in the clinical trial database, as well as the variability in placebo rates,
preclude reliable conclusions on the relative safety profiles among these drugs. Adults and
Pediatrics: Additional Data There are clinical trials and post-marketing reports with SSRIs and
other newer antidepressants, in both pediatrics and adults, of severe agitation-type adverse
events coupled with self-harm and harm to others. The agitation-type events include: akathisia,
agitation, emotional lability, hostility, aggression, depersonalization. In some cases, the events
occurred within several weeks of starting treatment. Rigorous clinical monitoring for suicidal
ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages.
This includes monitoring for agitation-type emotional and behavioural changes. Discontinuation
Symptoms Patients currently taking escitalopram should NOT be discontinued abruptly, due to
risk of discontinuation symptoms. At the time that a medical decision is made to discontinue an
SSRI or other newer antidepressant drug, a gradual reduction in the dose rather than an abrupt
cessation is recommended.
Discontinuation of Treatment with Escitalopram When discontinuing treatment, patients should be monitored
for symptoms that may be associated with discontinuation (e.g., dizziness, abnormal dreams, sensory disturbances
[including paraesthesias and electric shock sensations], agitation, anxiety, emotional indifference, impaired concentration,
headache, migraine, tremor, nausea, vomiting and sweating) or other symptoms that may be of clinical significance.
A gradual reduction in the dosage over several weeks, rather than abrupt cessation is recommended whenever possible.
If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should
be managed on the basis of the patients clinical response (see ADVERSE REACTIONS). Escitalopram Treatment
during Pregnancy-Effects on Newborns Post-marketing reports indicate that some neonates exposed to SSRIs
such as escitalopram and other antidepressants late in the third trimester have developed complications requiring prolonged
hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. When
treating a pregnant woman with escitalopram during the third trimester, the physician should carefully consider the potential
risks and benefits of treatment. The physician may consider tapering Cipralex
in the third trimester. Interference with

Cognitive and Motor Performance In a study with healthy volunteers, citalopram did not impair cognitive function
or psychomotor performance. However, psychotropic medications may impair judgement, thinking or motor skills.
Consequently, patients should be cautioned against driving a car or operating hazardous machinery until they are
reasonably certain that escitalopram does not affect them adversely.
ADDITIONAL PRECAUTIONS For complete details on the following precautions, please refer to the SUPPLEMENTAL
PRODUCT INFORMATION section: Carcinogenesis and Mutagenesis, Cardiovascular (Patients with Cardiac Disease), Endocrine
and Metabolism (Diabetic Patients), Hematologic (Bleeding Disorders), Hepatic/Biliary/Pancreatic (Hepatic Impairment),
Neurologic (Seizures, Serotonin Syndrome/Neuroleptic Malignant Syndrome (NMS)- like events), Psychiatric (Suicide,
Activation of Mania/Hypomania, Electroconvulsive Therapy (ECT), Renal (Hyponatremia, Renal Impairment), Special
Populations (Pregnant and Nursing Women, Complications following late third trimester exposure to SSRIs, Risk of PPHN
and exposure to SSRIs, Pediatrics, Geriatrics).
ADVERSE REACTIONS Adverse Events Observed in Controlled Trials Adverse Events Associated
with Discontinuation of Treatment: MDD Discontinuation due to adverse events was more common in the active
treatment groups (5.9% in escitalopram and 5.4% in citalopram) than in the placebo group (2.2%). The events that were
associated with discontinuation of escitalopram in 1% or more of patients at a rate of at least twice that of placebo were:
nausea (1.7% vs. 0.2%) and ejaculation failure (1.8% vs. 0.0% of male patients). GAD In GAD trials, 7.8% discontinued
treatment due to an adverse event, as compared to 3.2% of patients receiving placebo. Adverse events that were associated
with the discontinuation of at least 1% of patients treated with escitalopram, and for which the rate was higher than the
placebo rate, were: dizziness (1.2% vs. 0.2%), fatigue (1.1% vs. 0.2%) and nausea (1.8% vs. 0.2%). OCD In OCD
trials, discontinuation of treatment due to adverse events was reported for 9% and 11% of patients who were treated
with 10 mg/day or 20 mg/day escitalopram, respectively, compared to 5% receiving placebo. Adverse events that were
associated with discontinuation of at least 1% of patients treated with escitalopram, and for which the rate was higher
than the placebo rate, were: nausea (1.8% vs. 0.0%), insomnia (1.8% vs. 0.9%), and erectile dysfunction (1.1% vs. 0.0%).
Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the
adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be
compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful
for identifying drug-related adverse events and for approximating rates. Treatment-emergent adverse events in placebo-
controlled clinical trials for MDD: The most commonly observed adverse events (>5% and twice the rate of that seen in
placebo) in escitalopram-treated patients was: insomnia. Adverse reactions observed with escitalopram are in general mild
and transient. Treatment-emergent adverse events in placebo-controlled clinical trials for GAD: The most commonly
observed adverse events (>5% and twice the rate of that seen in placebo) in escitalopram-treated patients were: nausea,
fatigue, insomnia, delayed ejaculation. Treatment-emergent adverse events in placebo-controlled clinical trials for OCD:
The most commonly observed adverse events (>5% and twice the rate of that seen in placebo) in escitalopram-treated
patients were: fatigue, delayed ejaculation, hyperhidrosis. Weight Changes: Patients treated with escitalopram in short-term
controlled trials did not differ from placebo-treated patients with regards to clinically important change in body weight. In
one 24-week randomized clinical trial in patients with Social Anxiety Disorder, 8.0% of patients treated with escitalopram
and 3.2% of patients treated with placebo experienced weight gain of 7% or more. For more details on adverse events
reported during clinical trials or in post-marketing, see ADVERSE REACTIONS in the Product Monograph available on request.
To report suspected adverse reactions, contact Lundbeck Canada Medical Information & Pharmacovigilance at
1 866 880-4636 or (514) 844-8088. Suspected adverse reactions can also be reported to Health Canada at
1 866 234-2345 or faxed at 1 866 678-6789 or emailed at CanadaVigilance@hc-sc.gc.ca. They can also be mailed to:
Canada Vigilance National Office, Marketed Health Products Safety and Effectiveness Information Division, Marketed
Health Products Directorate, Health Products and Food Branch, Health Canada, Tunney's Pasture AL 0701C, Ottawa,
Ontario, K1A 0K9.
DRUG INTERACTIONS
Serious Drug Interactions
Monoamine Oxidase Inhibitors: see CONTRAINDICATIONS.
Pimozide: see CONTRAINDICATIONS.
Drug-Drug Interactions Monoamine Oxidase Inhibitors (MAOIs) Combined use of escitalopram and MAO
inhibitors is contraindicated (see CONTRAINDICATIONS; PRECAUTIONS Serotonin Syndrome/Neuroleptic Malignant
Syndrome (NMS)- like events). Cytochrome P450 Isozymes: Escitalopram: Using in vitro models of human liver
microsomes, the biotransformation of escitalopram to its demethylated metabolites was shown to depend on three parallel
pathways (CYP2C19, CYP3A4 with a smaller contribution from CYP2D6)(see ADMINISTRATION, CYP2C19 Poor metabolizers).
Studies also indicate that escitalopram is a very weak or negligible inhibitor of human hepatic isoenzyme CYP1A2, 2C9,
2C19, 2E1, and 3A4, and a weak inhibitor of 2D6. Although escitalopram has a low potential for clinically significant drug
interactions, caution is recommended, when escitalopram is co-administered with drugs that are mainly metabolized by
CYP2D6, and that have a narrow therapeutic index. The possibility that the clearance of escitalopram will be decreased
when administered with the following drugs in a multiple-dose regimen should be considered: potent inhibitors of CYP3A4
(e.g., fluconazole, ketoconazole, itraconazole, erythromycin), or potent inhibitors of CYP2C19 (e.g., omeprazole,
esomeprazole, fluvoxamine, lansoprazole, ticlopidine). Caution should be exercised at the upper end of the dosage range
of escitalopram when it is co-administered with CYP2C19 inhibitors. In addition, a single-dose study of escitalopram
co-administered with a multiple-dose regimen of cimetidine led to significant changes in most of the pharmacokinetic
parameters of escitalopram. The overall metabolic pathways for escitalopram and citalopram are qualitatively similar and the
interaction potential for escitalopram is expected to closely resemble that of citalopram. Thus, this allows for extrapolation
to previous studies with citalopram. CNS drugs Drug interactions have not been specifically studied between either
escitalopram or racemic citalopram and other centrally acting drugs. Given the primary CNS effects of escitalopram, caution
should be used as with other SSRIs when escitalopram is taken in combination with other centrally acting drugs.
Serotonergic Drugs: Based on the mechanism of action of escitalopram and the potential for serotonin syndrome,
caution is advised when Cipralex
is coadministered with other drugs or agents that may affect the serotonergic
neurotransmitter systems, such as tryptophan, triptans, serotonin reuptake inhibitors, lithium, tramadol, or St. John's Wort
(see SUPPLEMENTAL PRODUCT INFORMATION, PRECAUTIONS Serotonin Syndrome/Neuroleptic Malignant Syndrome
Patient Selection Criteria
Safety Information
Prescribing Summary
10 mg and 20 mg tablets
Considering surgery in treatment resistant migraine patients
August 2011 n17
(Plast Reconstr Surg Aug. 2009;
124(2):461-468.), those who had
such trigger sites were random-
ized in double-blind fashion for
either sham or actual surgery.
While patients in both study
arms experienced at least 50%
reduction in migraine head ache,
there was a statistically significant
difference (p<0.05) between the
two groups on that outcome, a
difference that favoured those
who had actual surgery.
Moreover, there was a highly
statistically significant differ-
ence across the two groups in
those patients who had com-
plete elimination of migraine
headaches, favouring those
who underwent surgical
decompression, p<0.001.
Multiple basic science stud-
ies are underway in our lab to
shed some light into the ration-
al for the efficacy of the surgi-
cal treatment of migraine
headaches, he said.
Non-proprietary names of ther-
apies: Botulinum Toxin Type A,
(Botox, Allergan)
Migraine
and obesity
a
s
al
g
rg
ntia
m
ca
ys
m
ical
bout
ces
s at
.org
18 nAugust 2011
done.
If people use nicotine
replacement after theyve start-
ed varenicline, theoretically it
will block nicotine replace-
ment, he said, but he added
that anecdotal evidence sug-
gests some effectiveness when
combined with nicotine gum or
lozenges for the patient who
has only the occasional ciga-
rette while on varenicline.
He emphasized though that
in general, varenicline should
not be used with nicotine
replacement therapy.
Varenicline generally
should be used by itself. You
can make a case for its combi-
nation with bupropion, but its
very difficult to make a case for
its use during nicotine replace-
ment, he said.
Between the two approach-
es, he said, each has advantages.
From a safety profile, nico-
tine replacement wins hands
down, said Dr. Selby.
And from an efficacy per-
spective, though we dont have
a good head to head compari-
son study... varenicline appears
to be the most effective.
Read about Dr. Selby
in the news at
http://ow.ly/65C3P
Mechanisms
of addiction
Nicotine replacement therapy and its role in pharmacological treatments
prepared to use varenicline.
If theyve tried NRT,
bupropion, and they have a
really compelling need to stop,
such as COPD, then Im going
to bring out the big guns.
He said that varenicline is gen-
erally contraindicated with nico-
tine replacement therapy, since it
acts as an antagonist to block the
nicotine receptors if given after
the person is on the patch.
It doesnt make a whole lot
of sense, because with the stan-
dard dosing of varenicline,
almost all the nicotinic recep-
tors are saturated. But, thats
not definitive, said Dr. Selby.
Varenicline is a partial agonist
of the a42 subtype of the nico-
tinic acetylcholine receptor. It
also acts on a34 and weakly on
a32 and a6-containing receptors.
There may be other recep-
tors subtypes that may not be
blocked by varenicline, but
those studies havent been
(NMS)- like events). Concomitant use of Cipralex
and MAO inhibitors (including linezolid, an antibiotic which is a

reversible non-selective MAO inhibitor) is contraindicated (see CONTRAINDICATIONS). Triptans (5HT1 agonists):
Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake
inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. If concomitant treatment
with Cipralex
and a triptan is clinically warranted, careful observation of the patient is advised, particularly during
treatment initiation and dose increases (see SUPPLEMENTAL PRODUCT INFORMATION, PRECAUTIONS Serotonin
Syndrome/Neuroleptic Malignant Syndrome (NMS)- like events). Racemic Citalopram As escitalopram (Cipralex
)
is the active isomer of citalopram (Celexa
), the two drugs should not be taken together. Alcohol use Although
citalopram did not potentiate the cognitive and psychomotor effects of alcohol in volunteers, the concomitant use of
alcohol in depressed patients taking escitalopram is not recommended. Polymorphism It has been observed that poor
metabolisers with respect to CYP2C19 have twice as high a plasma concentration of escitalopram as extensive
metabolisers (see ADMINISTRATION, CYP2C19 Poor metabolizers). Although no significant change in exposure was
observed in poor metabolizers with respect to CYP2D6, caution is recommended when escitalopram is co-administered
with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index.
Established or Predicted Drug-Drug Interactions with Escitalopram Cimetidine: Caution should be
exercised when used concomitantly with cimetidine. A reduction in the dose of escitalopram may be necessary based
on clinical judgement. Imipramine/Desipramine: substrate for CYP2D6: Resulted in a 50% increase of
desipramine concentrations. Concomitant treatment with escitalopram and imipramine/desipramine should be undertaken
with caution. Metoprolol: substrate for CYP2D6: Resulted in a 50% increase in the peak plasma levels of the
-adrenergic blocker with no clinically significant effects on blood pressure or heart rate. Omeprazole: CYP2C19
inhibitor: Caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole). A reduction
in the dose of escitalopram may be necessary based on clinical judgement. Ritonavir: substrate for CYP3A4:
Combined administration did not affect the pharmacokinetics of either ritonavir or escitalopram. Carbamazepine: Since
carbamazepine is a microsomal enzyme inducer, the possibility that carbamazepine may increase the clearance of
escitalopram should be considered if the two drugs are given concomitantly. Lithium: Since lithium may increase
serotonergic neurotransmission, concomitant treatment with escitalopram should be undertaken with caution. Drug-Food
Interaction Although there is a theoretical possibility of pharmacokinetic drug interactions resulting from co-administration
of escitalopram with grapefruit juice, the onset of an interaction is considered unlikely. Drug-Herb Interactions St-Johns
Wort: In common with other SSRIs and newer antidepressants, pharmacodynamic interactions between escitalopram and
the herbal remedy St-Johns Wort may occur and may result in undesirable side effects.
Dosing Consideration Cipralex
(escitalopram oxalate) is not indicated for use in children under

18 years of age (see WARNINGS AND PRECAUTIONS Potential Association with Behavioural and Emotional Changes,
Including Self-Harm). General: Escitalopram should be administered as a single daily dose, with or without food.
Recommended Dose and Dosage Adjustment Adults MDD/GAD/OCD Escitalopram should be administered
as a single oral dose of 10 mg daily. Depending on individual patient response, an increase in the dose to a maximum of
20 mg daily should be considered. Where initial sensitivity to adverse events may be a concern, escitalopram could be
started at 5 mg daily and titrated upwards as tolerated. Treatment of Pregnant Women During the Third
Trimester (see WARNINGS AND PRECAUTIONS). Elderly Patients A longer half-life and decreased clearance have been
demonstrated in the elderly, therefore lower doses and a lower maximum dose should be considered. It may be desirable to
start at 5 mg daily and titrate upwards as needed and tolerated. Renal Impairment No dosage adjustment is necessary
for patients with mild or moderate renal impairment. Since no information is available on the pharmacokinetic or pharma-
codynamic effects of either escitalopram or citalopram in patients with severely reduced renal function (creatinine clearance
<30mL/min), escitalopram should be used with caution in these patients. Hepatic Impairment Dosages should be
restricted to the lower end of the dose range in patients with mild to moderate hepatic insufficiency. Accordingly, an initial
single oral dose of 5 mg daily is recommended. Subsequently, the dose may be increased based on the patients response and
clinical judgement. A daily dose of 10 mg is the recommended maximum dose for most patients with hepatic impairment.
No information is available about the pharmacokinetics of escitalopram in patients with severe hepatic impairment (Child-Pugh
Criteria C). Escitalopram should be used with additional caution in patients with severe hepatic impairment. CYP2C19 Poor
metabolizers The metabolism of escitalopram is mainly mediated by CYP2C19. For patients who are known to be poor
metabolizers with respect to CYP2C19, an initial dose of 5 mg daily is recommended. The dose may be increased based
on the patients response and clinical judgement. Long-Term Treatment During long-term therapy, the dosage should be
maintained at the lowest effective level and patients should be periodically reassessed to determine the need to continue treat-
ment. Switching Patients To or From a Monoamine Oxidase Inhibitor (MAOI) (see CONTRAINDICATIONS).
Discontinuation of Escitalopram Treatment Symptoms associated with the discontinuation or dosage reduction of
escitalopram have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment
or during dosage reduction (see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS). Children (see WARNINGS
AND PRECAUTIONS General, Potential Association with Behavioural and Emotional Changes, Including Self-Harm).
Missed Dose In the event that a dose is missed, the patient should take the next dose when it is due.
OVERDOSAGE: See SUPPLEMENTAL PRODUCT INFORMATION section.
STORAGE AND STABILITY: Escitalopram tablets should be stored in a dry place at room temperature (15 and 30C).
DOSAGE FORMS, COMPOSITION AND PACKAGING: Escitalopram tablets contain escitalopram oxalate
corresponding to 10 mg or 20 mg escitalopram, and the following non medicinal ingredients: colloidal silicon
dioxide, croscarmellose sodium, hydroxypropyl methyl cellulose, magnesium stearate, microcrystalline cellulose,
polyethylene glycol 400, talc, titanium dioxide (white E-171). Availability of dosage forms: 10 mg tablets:
Each film-coated, white, oval, scored tablet, marked with EL on one side, contains: escitalopram 10 mg (as escitalopram
oxalate). Blister packages of 7 and 30. Bottle of 100. 20 mg tablets: Each film-coated, white, oval, scored tablet,
marked with EN on one side, contains: escitalopram 20 mg (as escitalopram oxalate). Blister packages of 30.
Consult Product Monograph for full prescribing information.
SUPPLEMENTAL PRODUCT INFORMATION
CONTRAINDICATIONS: Monoamine Oxidase Inhibitors Cases of serious reactions have been reported in patients receiving selective serotonin reuptake
inhibitors (SSRIs) in combination with a monoamine oxidase inhibitor (MAOI) or the reversible MAOI (RIMA), moclobemide, and in patients who have recently discontinued
an SSRI and have been started on a MAOI (see DRUG INTERACTIONS). With the co-administration of an SSRI with MAOI, there have been reports of serious, sometimes
fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible fluctuations of vital signs, and mental status changes, including extreme
agitation progressing to delirium and coma. Some cases presented with features resembling serotonin syndrome.
PRECAUTIONS The following additional precautions are listed alphabetically. Carcinogenesis and Mutagenesis See complete product monograph.
Cardiovascular Patients with Cardiac Disease Neither escitalopram nor racemic citalopram has been systematically evaluated in patients with a recent history
of myocardial infarction or unstable heart disease. In line with other SSRIs, including racemic citalopram, escitalopram causes statistically significant, but clinically
unimportant decrease in heart rate. In patients <60 years old, the mean decrease with escitalopram was approximately 2.3 bpm, while in patients 60 years old, the
mean decrease was approximately 0.6 bpm. Endocrine and Metabolism Diabetic Patients Neither escitalopram nor racemic citalopram has been systematically
evaluated in diabetic patients; in the case of citalopram, diabetes constituted an exclusion criterion. Rare events of hypoglycaemia were reported for citalopram. Treatment
with an SSRI in patients with diabetes may alter glycaemic control (hypoglycaemia and hyperglycaemia). Escitalopram should be used with caution in diabetic patients on
insulin or oral hypoglycaemic drugs. Hematologic Bleeding Disorders SSRIs and serotonin/norepinephrine reuptake inhibitors (SNRIs), including Cipralex
, may
increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk.
Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake
and the occurrence of gastrointestinal bleeding. There have been reports of bleeding events ranging from ecchymoses, hematomas, epistaxis, and petechiae to
life-threatening haemorrhages, associated with treatment with SSRIs and SNRIs. Caution is advised in patients taking SSRIs and SNRIs, particularly in concomitant use
with drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, anticoagulants, platelet aggregation
inhibitors, acetylsalicylic acid and NSAIDs), as well as in patients with a history of bleeding disorders or predisposing conditions (e.g., thrombocytopenia).
Hepatic/Biliary/Pancreatic Hepatic Impairment Based on a study conducted with escitalopram in patients with mild to moderate hepatic impairment, the
half-life was approximately doubled and the exposure was increased by approximately two third, compared to subjects with normal liver function. Consequently, the use
of escitalopram in hepatically impaired patients should be approached with caution and a lower dosage is recommended (see ADMINISTRATION). Neurologic Seizures
Escitalopram has not been systematically evaluated in patients with a seizure disorder. These patients were excluded from the clinical studies. In clinical trials with
escitalopram, convulsions have been reported very rarely (2 out of 3981 patients) in association with treatment with escitalopram. From post-marketing data, the reporting
of seizures with escitalopram is comparable to that of other antidepressants. Like other antidepressants, escitalopram should be used with caution in patients with a history
of seizure disorder. Serotonin Syndrome/Neuroleptic Malignant Syndrome (NMS)-like events On rare occasions serotonin syndrome or neuroleptic
malignant syndrome-like events have occurred in association with treatment with SSRIs, including escitalopram, particularly when given in combination with other
serotonergic and/or neuroleptic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with Cipralex
should be discontinued if such events

(characterized by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes
including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Cipralex
should not
be used in combination with MAO inhibitors or serotonin-precursors (such as L-tryptophan, oxitriptan) and should be used with caution in combination with other serotonergic
drugs (triptans, certain tricyclic antidepressants, lithium, tramadol, St. Johns Wort) due to the risk of serotonergic syndrome (see CONTRAINDICATIONS and DRUG
INTERACTIONS, Serotonergic Drugs, Triptans). Psychiatric Suicide The possibility of a suicide attempt is inherent in depression and may persist until remission occurs.
Therefore, high-risk patients should be closely supervised throughout therapy with consideration to the possible need for hospitalization. In order to minimize the opportunity
for overdosage, prescription for escitalopram should be written for the smallest quantity of drug consistent with good patient management. Because of the well established
comorbidity between depression and other psychiatric disorders, the same precautions observed when treating patients with depression should be observed when treating
patients with other psychiatric disorders (see WARNINGS AND PRECAUTIONS General, Potential Association with Behavioural and Emotional Changes, Including Self-
Harm). Activation of Mania/Hypomania In placebo-controlled trials of escitalopram oxalate activation of mania/hypomania was reported in one patient of the
n=715, treated with escitalopram and in a small proportion of patients treated with citalopram, and with other marketed antidepressants. Escitalopram should be used
with caution in patients with a history of mania/hypomania. Electroconvulsive Therapy (ECT) The safety and efficacy of the concurrent use of either escitalopram
or citalopram and ECT have not been studied. Renal Hyponatremia As with other antidepressants, cases of hyponatremia and SIADH (syndrome of inappropriate
antidiuretic hormone secretion) have been reported with escitalopram and racemic citalopram as a rare adverse event. The majority of these occurrences have been
in elderly individuals, some in patients taking diuretics or who were otherwise volume-depleted. Elderly female patients in particular seem to be a group at risk.
Renal Impairment (see ADMINISTRATION). Special Populations Pregnant and Nursing Women: The safety of escitalopram during human pregnancy and
lactation has not been established. Therefore, escitalopram should not be used during pregnancy, unless the potential benefit to the patient outweighs the possible risk to
the foetus. Studies with escitalopram have not been performed in nursing mothers, but it is known that citalopram is excreted in human milk and it is expected that
escitalopram is also excreted into breast milk. Escitalopram should not be administered to nursing mothers unless the expected benefits to the patient outweigh the possible
risk to the child. Complications following late third trimester exposure to SSRIs: Post-marketing reports indicate that some neonates exposed to SSRIs
such as Cipralex
and other antidepressants late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube
feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnoea, seizures, temperature
instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent
with either a direct toxic effect of SSRIs and other newer antidepressants, or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical
picture is consistent with serotonin syndrome (see SUPPLEMENTAL PRODUCT INFORMATION, PRECAUTIONS Serotonin Syndrome/Neuroleptic Malignant Syndrome
(NMS)- like events). Risk of PPHN and exposure to SSRIs: In one epidemiological case-control study on persistent pulmonary hypertension (PPHN) with n = 377
infants with PPHN and n = 836 matched control infants, PPHN was six times more common in babies whose mothers took an SSRI antidepressant after the 20th week
of pregnancy compared to babies whose mothers did not take an antidepressant. The study was too small to determine relative risks among the specific SSRIs. This
information is considered to be preliminary at this time. The absolute risk of PPHN in the general population is reported to be 1 2 per 1000. Pediatrics (see WARNINGS
AND PRECAUTIONS, General, Potential Association with Behavioural and Emotional Changes, Including Self-Harm). Geriatrics (see ADMINISTRATION).
OVERDOSAGE Clinical data on escitalopram overdose are limited and many cases involve concomitant overdoses of other drugs. In the majority of cases mild or no
symptoms have been reported. Fatal cases of escitalopram overdose have rarely been reported with escitalopram alone (doses unknown); the majority of cases have involved
multiple drug overdose. Doses up to 800 mg of escitalopram alone have been taken without any severe symptoms. In clinical trials with citalopram, there were no reports
of fatal citalopram overdoses of up to 2000 mg. Post-marketing reports of drug overdoses involving racemic citalopram have included fatalities with citalopram alone. In
many cases, details regarding the precise dose of racemic citalopram or combination with other drugs and/or alcohol are often lacking. However, three fatalities with known
overdoses of citalopram alone have been reported in the literature, (doses of 2800 mg, 2880 mg, and 3920 mg) although survival has also been reported with overdoses
of up to 5200 mg. In comparing the data from racemic citalopram with that of escitalopram, it is important to be aware that the latter product is expected to have similar
pharmacodynamic effects at a lower dose of the racemic product. Fatal cases of serotonin syndrome have been reported in patients who took overdoses of moclobemide
(Manerix
) and racemic citalopram. Symptoms most often accompanying overdose of racemic citalopram included dizziness, sweating, nausea, vomiting, tremor, and
somnolence. In more rare cases, observed symptoms included confusion, loss of consciousness, convulsions, coma, sinus tachycardia, cyanosis, hyperventilation and
rhabdomyolysis and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and one possible case of Torsades de pointes). Management of
Overdose As with racemic citalopram, there is no specific antidote to escitalopram. Treatment is symptomatic and supportive. Establish and maintain an airway to ensure
adequate ventilation and oxygenation. Gastric lavage and use of activated charcoal should be considered as soon as possible after oral ingestion. Cardiac and vital sign
monitoring are recommended, along with general symptomatic and supportive measures. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis,
haemoperfusion and exchange transfusion are unlikely to be of benefit. In managing overdosage, the possibility of multiple drug involvement must be considered.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
Cipralex
tablets are made by:

H. Lundbeck A/S, Ottiliavej 9, DK-2500, Copenhagen, Denmark
Product License Holder/Distributor:
Lundbeck Canada Inc., 1000 de la Gauchetire Street West, Suite 500, Montreal (Quebec), H3B 4W5, Canada 1-800-586-2325 www.lundbeck.ca
Product Monograph available on request.
Reference: 1. Cipralex Product Monograph, June 12, 2009. Lundbeck Canada Inc.
Registered trademark of Lundbeck Canada Inc.
ADMINISTRATION
CIP-253-09E
the use of prescription thera-
pies, such as opioids.
Current responses to drug
addiction like methadone are
palliative, and not actually treat-
ment for drug addiction. We
want to aim at reversing what is
happening in the brain, said
Dr. Dumont.
The potential therapy he
envisions could be added to an
existing drug like oxycodone,
according to Dr. Dumont.
It could be an adjuvant to a
painkiller, said Dr. Dumont.
It would not interfere with the
painkillers ability to reduce
pain, but it would reduce its
addictive properties.
Read a recent article by
Dr. Dumont at
http://ow.ly/65Bkz
PRESCRIBING SUMMARY
THERAPEUTIC CLASSIFICATION
Muscle relaxant, peripherally acting agent
INDICATIONS AND CLINICAL USE
XEOMIN
is indicated in adults for the symptomatic management of:

blepharospasm; cervical dystonia of a predominantly rotational form
(spasmodic torticollis); post-stroke spasticity of the upper limb.
XEOMIN
as a treatment for focal spasticity has been studied in association with

usual standard care regimens and is not intended as a replacement for these treat-
ment modalities.
XEOMIN
is not likely to be effective at a joint affected by a xed contracture.

XEOMIN
may only be used by physicians with suitable qualications and proven

experience in the application of Botulinum toxin type A and in the use of the neces-
sary equipment, e.g. EMG (electromyography).
CONTRAINDICATIONS
Hypersensitivity to Botulinum neurotoxin type A or to any of the excipients. Gen-
eralised disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syn-
drome). Presence of infection at the proposed injection site.
SERIOUS WARNINGS AND PRECAUTIONS
The term "unit" or "b" uon which dosinq is based, is a secilc measure-
ment of toxin activity that is unique to XEOMIN
. Therelore, the "unit" or "b"

used to describe XEOMIN
activity are different from those used to describe

that of other botulinum toxin preparations and the units representing XEOMIN

activity are not interchangeable with other products.
Follow the recommended dosaqe and lrequency ol administration lor XE0Mh

(See DOSAGE AND ADMINISTRATION).
General
Patients and caregivers should be advised to seek immediate medical
consultation if swallowing, speech, or respiratory disorders arise.
In very rare cases severe adverse events like muscle weakness, dysphagia
or aspiration pneumonia with a suspected causal relationship to toxin spread
have been reported with the use of botulinum toxin. Also very rare cases of
adverse events with a fatal outcome have been reported. Patients with
a neurological underlying disease or swallowing, speech or respiratory
difculties have an increased risk for these adverse drug reactions and should be
treated and supervised very carefully.
An anaphylactic reaction may occur rarely after injection of Botulinum neurotoxin
tye A (See ABvERSE REACT0hS). Adrenaline and other medical aids lor treatinq
anaphylaxis should be available.
Extra caution is required when injecting at sites close to sensitive structures such
as the carotid artery and lung apices.
XEOMIN
should be used with caution: in patients suffering from amyotrophic lateral

sclerosis or other diseases which result in peripheral neuromuscular dysfunction; in
targeted muscles which display pronounced weakness or atrophy.
GASTROINTESTINAL
Spasmodic torticollis
Patients should be informed that injections of XEOMIN
for the management of

spasmodic torticollis may cause mild to severe dysphagia with the risk of aspiration
and dyspnoea. Medical intervention may be necessary (e.g. in the form of a gas-
tric leedinq tube) (See ABvERSE REACT0hS). Byshaqia can last lor u to two to
three weeks after injection. Patients with smaller neck muscle mass, or patients who
require bilateral injections into the sternocleidomastoid muscles are at greater risk.
The occurrence ol dyshaqia is attributable to the sread ol the harmacoloqical el-
fect of Botulinum toxin as the result of the neurotoxin spread into the oesophageal
musculature.
Hematologic
XEOMIN
should be used with caution if bleeding disorders of any type occur. It

should be used with caution in patients receiving anticoagulant therapy.
OPHTHALMOLOGIC
Blepharospasm
Because of the anticholinergic effect of Botulinum toxin type A, XEOMIN
should be
used with caution in patients at risk of developing an angle closure glaucoma.
In order to prevent ectropion, injections into the lower lid area should be avoided, and
viqorous treatment ol any eithelial delect is necessary. This may require rotective
drops, ointments, soft bandage contact lenses, or closure of the eye by patching or
similar means.
Reduced blinking following XEOMIN
injection into the orbicularis muscle can

lead to corneal exposure, persistent epithelial defects and corneal ulceration,
especially in patients with cranial nerve disorders (facial nerve). Careful testing of cor-
neal sensation should be performed in patients with previous eye operations.
Ecchymosis easily occurs in the soft tissues of the eyelid. Immediate gentle pressure
at the injection site can limit that risk.
SPECIAL POPULATIONS
Pregnant Women:
There have been no studies in reqnant women. Studies in animals have shown
reroductive toxicity (See T0XC0L0Y). The otential risk lor humans is
unknown.
XEOMIN
should not be used during pregnancy unless clearly necessary and unless
the potential benet justies the risk.
Nursing Women:
t is not known whether Botulinum toxin tye A is excreted into the breast milk. There-
fore, the use of XEOMIN
during lactation is not recommended.

Pediatrics (<18 years of age):
No data is available on the use of XEOMIN
in children and it is therefore not currently

recommended in this age group.
Geriatrics (>65 years of age):
Although clinical studies included a number of patients over the age of 65, no clinical
trials specically designed for elderly patients have been performed.
Initial dosing should begin at the lowest recommended dose for the specic indi-
cation and be cautiously titrated within the recommended range for optimal patient
outcome.
ADVERSE REACTIONS
Adverse Drug Reaction Overview
bndesirable ellects associated with the theraeutic use ol Botulinum toxin tye
A are mainly related to the diffusion of Botulinum neurotoxin type A from the tar-
get muscle to adjacent muscles. Such undesirable effects are rare, and most are
localized in close proximity to the injection site; systemic side effects are un-
common. Intramuscular injection into neck muscles for treatment of cervical
dystonia occasionally results in transient dysphagia and a general weakness in the
neck muscles. Treatment ol bleharosasm by eriocular injection can result in
ptosis and diplopia. Intramuscular injections of Botulinum toxin type A for up-
per limb spasticity were reported to be commonly associated with local reac-
tions like hypertonia, ecchymosis, purpura, pain in shoulder, arm or hand, muscle
weakness, bleeding and itching after administration at the injection site.
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specic conditions the adverse reac-
tion rates observed in the clinical trials may not reect the rates observed in practice
and should not be compared to the rates in the clinical trials of another drug. Adverse
drug reaction information from clinical trials is useful for identifying drug-related ad-
verse events and for approximating rates.
In the 6 studies conducted to provide data on the safety of XEOMIN
1082 subjects
were treated with trial medications (XEOMIN
, active comparator or placebo). See

product monograph for study parameters.
Table 1: Adverse Drug Reactions Reported in *1% of Cervical Dystonia Patients
System organ class
Preferred term
Number of subjects (%)
XEOMIN

N=272
Active Comparator 1
(Botulinum toxin
type A-complex)
N=244
Gastrointestinal disorders 24 (8.8) 15 (6.1)
Dysphagia 24 (8.8) 15 (6.1)
Musculoskeletal &
connective tissue disorders
9 (3.3) 2 ()1)
Muscular weakness 4 (1.5) 1 ()1)
Neck pain 5 (1.8) 1 ()1)
Powder for solution for injection, 100 LD
50
units per vial
Prescribing Summary
Patient Selection Criteria
Safety Information
(Clostridium Botulinum Neurotoxin Type A (150 kD), free from complexing proteins)
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Table 2: Adverse Drug Reactions Reported in *1% of Blepharospasm Patients
System organ class
Preferred term
XEOMIN

N=148
Active Comparator 1
(Botulinum toxin
type A-complex)
N=152
Eye disorders 12 (8.1) 12 (7.9)
Dry eye 3 (2.0) 0 (0.0)
Eyelid oedema 0 (0.0) 2 (1.3)
Eyelid ptosis 9 (6.1) 7 (4.6)
Vision blurred 0 (0.0) 3 (2.0)
Table 3: Adverse Drug Reactions Reported in *1% of Patients with Post-stroke
Spasticity of the Upper Limb (Double-blind Period)
System organ class
Preferred term
XEOMIN

N=73
Placebo
N=75
Gastrointestinal disorders 0 (0.0) 1 (1.3)
Dysphagia 0 (0.0) 1 (1.3)
General dis. & admin. site conditions 0 (0.0) 1 (1.3)
Injection site pain 0 (0.0) 1 (1.3)
Nervous system dis. 1 (1.4) 0 (0.0)
Headache 1 (1.4) 0 (0.0)
Table 4: Adverse Drug Reactions Reported in *1% of Patients with Post-Stroke
Spasticity of the Upper Limb (Open-Label Extension Period)
System organ class
Preferred term
XEOMIN
Number of Subjects (%)

N= 145
Gastrointestinal disorders
Dysphagia 2 (1.4)
General dis. & admin. site conditions
Injection site pain 4 (2.8)
Musculoskeletal and connective tissue
disorders
Muscular weakness 5 (3.4)
Pain in extremity 2 (1.4)
To reort an adverse reaction lease notily health Canada at 18GG2842845 or
MERZ Canada at 1-866-815-8715.
Drug-Drug Interactions
Theoretically, the ellects ol Botulinum toxin may be otentiated by aminoqlycoside anti-
biotics or other medicinal products that interfere with neuromuscular
transmission, e.g. tubocurarine-type muscle relaxants.
Therelore, the concomitant use ol XE0Mh
with aminoglycosides, polymyxins,

tetracyclines, linomycin, spectinomycin or any other drugs that interfere with neuro-
muscular transmission requires special care. Peripheral muscle relaxants should be
used with caution, if necessary reducing the starting dose of relaxant, or using an
intermediate-acting substance such as vecuronium or atracurium rather than sub-
stances with longer lasting effects.
4-Aminochinolines may reduce the effect of XEOMIN
.
Recommended Dose and Dosage Adjustment
Blepharospasm
The initial recommended dose is 1.25 to 2.5 b (O.O5O.1 mL volume) er
injection site. The initial dose should not exceed 25 b er eye. n the manaqement ol
bleharosasm, total dosinq should not exceed 7O b and the eriod between each
treatment session is recommended to be at least every 12 weeks.
The median time to lrst onset ol ellect is observed within lour days alter
injection. The ellect ol each treatment qenerally lasts aroximately 84
months, however, it may last siqnilcantly lonqer or shorter. The treatment
can be reeated il required. There is limited exerience in treatment ol naive
patients and in long-term repeat-dose treatment.
At repeat treatment sessions, the dose may be increased up to two-fold (as long as
the total dose ol 7O b is not exceeded) il the resonse to the initial treatment is con-
sidered insufcient usually dened as an effect that does not last longer than two
months. However, there appears to be no additional benet obtainable from injecting
more than 5.O b er site. hormally, no additional benelt is conlerred by treatinq more
frequently than every three months.
In the management of spasmodic torticollis, XEOMIN
dosing must be tailored

to the individual patient, based on the patients head and neck position, loca-
tion of possible pain, muscle hypertrophy, patients body weight, and response
to the injection. A suitable sterile needle (e.g. 25-30 gauge/0.30-0.50 mm) is
used for injections into supercial muscles, and an e.g. 22 gauge/0.70 mm nee-
dle may be used for injections into deeper musculature. An injection volume of
approximately 0.1 to 0.5 mL per injection site is recommended.
n ractice, the usual total dose does not exceed 2OO b. Boses ol u to 8OO b may be
qiven. ho more than 5O b should be qiven at any one injection site.
The median lrst onset ol ellect is observed within seven days alter injection. The
effect of each treatment generally lasts approximately 3-4 months; however, it may
last siqnilcantly lonqer or shorter. The eriod between each treatment session is
recommended to be at least 12 weeks. There is limited exerience in treatmentnaive
patients and in long-term repeat-dose treatment.
Post-stroke Spasticity of the Upper Limb
Reconstituted XEOMIN
is injected using a suitable sterile needle (e.g.

26 gauge/0.45 mm diameter/37 mm length, for supercial muscles and a
longer needle, e.g. 22 gauge/0.7 mm diameter/75 mm length, for deeper
musculature). An injection volume of approximately 0.2 to 1 mL per injection site is
recommended, but it can be exceeded to 1.5 mL in selected cases.
The doses (units) usually administered in the manaqement ol oststroke
sasticity ol the uer limb are resented in Table 5.
Table 5: Dosage guide for the management of post-stroke spasticity of the up-
per limb
Clinical Pattern
Muscle
Units
Flexed Wrist (Total) 90
Flexor carpi radialis 50
Flexor carpi ulnaris 40
Clenched Fist (Total) 80
Flexor digitorum supercialis 40
Flexor digitorum profundus 40
Flexed Elbow (Total) 130-190
Brachioradialis 60
Biceps 80
Brachialis 50
Pronated Forearm (Total) 25-65
Pronator quadratus 25
Pronator teres 40
Thumb-in-Palm (Total) 10-40
Flexor pollicis longus 20
Adductor pollicis 10
Flexor pollicis brevis/
Opponens pollicis
10
Total dosinq should not exceed 4OO units er treatment session involvinq
different muscles.
Initial dosing should begin at the lowest recommended dose for the specif-
ic indication and be cautiously titrated within recommended dose range for
optimal patient outcome.
The median time to lrst onset ol ellect is observed within lour days alter injection.
The ellect ol each treatment qenerally lasts aroximately 8 months, however, it
may last siqnilcantly lonqer or shorter. The eriod between each treatment session
is recommended to be at least 12 weeks.
The multile oint injection technique into tarqet muscles with diserse
innervation zones can reduce undesirable effects and, at the same time, may reach
more intrafusal bres.
Blepharospasm
After reconstitution, the XEOMIN
solution is injected using a suitable

sterile needle (e.g. 27-30 gauge/0.30-0.40 mm). Electromyographic guidance is not
necessary. An injection volume of approximately 0.05 to 0.1 mL is recommended.
XEOMIN
is injected into the medial and lateral orbicularis oculi of the upper lid and
the lateral orbicularis oculi of the lower lid. Additional sites in the brow area, the
lateral orbicularis and in the upper facial area may also be injected if spasms here
interfere with vision.
Administration
Injections near the levator palpebrae superioris should be avoided to reduce the oc-
currence of ptosis. Diplopia may develop as a result of Botulinum neurotoxin type A
diffusion into the inferior oblique. Avoiding medial injections into the lower lid may
reduce this adverse reaction.
In the management of spasmodic torticollis, XEOMIN
is usually injected into

the sternocleidomastoid, levator scapulae, scalenus, splenius capitis, and/
or the trae/ius muscle(s). This list is not exhaustive as any ol the muscles
responsible for controlling head position may be involved and therefore
require treatment. If difculties arise isolating single muscles, injec-
tions should be erlormed usinq electromyoqrahic quidance. The muscle
mass and the degree of hypertrophy or atrophy are factors to be taken into
consideration when selecting the appropriate dose.
Multiple injection sites permit XEOMIN
more uniform coverage of the innervated areas

ol the dystonic muscle and are esecially uselul in larqer muscles. The otimum
number of injection sites is dependent upon the size of the muscle to be chemically
denervated.
The sternocleidomastoid should not be injected bilaterally as there is an
increased risk of adverse reactions (in particular dysphagia) when bilateral injec-
tions or doses in excess ol 1OO b are administered into this muscle.
Post-stroke Spasticity of the Upper Limb
Localisation of the involved muscles with electromyographic guidance or nerve
stimulation techniques may be necessary. Multiple injection sites may allow
XEOMIN
to have more uniform contact with the innervation areas of the muscle and
are especially useful when larger muscles are injected.
The exact dosaqe and number ol injection sites should be tailored to the individual a-
tient based on the size, number and location of muscles to be treated, the severity of
spasticity, and the presence of local muscle weakness. Initial dosing should begin at
the lowest recommended dose and be cautiously titrated within the recommended
dose range for optimal patient outcome.
Reconstitution
This medicinal roduct must not be mixed with other medicinal roducts
except those mentioned below.
XEOMIN
is reconstituted prior to use with sterile unpreserved sodium chloride 9 mg/

mL (0.9%) solution for injection. Reconstitution and dilution should be performed
in accordance with good clinical practice guidelines, particularly with respect to
asepsis.
It is good practice to perform vial reconstitution and syringe preparation
over plastic-lined paper towels to catch any spillage. An appropriate amount
ol solvent (Table G) is drawn u into a syrinqe. The exosed ortion ol the
rubber stopper of the vial is cleaned with alcohol (70%) prior to insertion of the
needle. The solvent must be injected qently into the vial. The vial must be discarded,
if the vacuum does not pull the solvent into the vial. Reconstituted XEOMIN
is a
clear colourless solution free of particulate matter.
XEOMIN
should not be used if the reconstituted solution (prepared as above) has

a cloudy appearance or contains occular or particulate matter.
Table 6: Possible Dilutions of XEOMIN
in the Reconstituted Solution

Solvent added
(sodium chloride 9 mg/mL (0.9%)
solution for injection
Resulting dose in units
per 0.1 mL
0.5 mL
1.0 mL
2.0 mL
4.0 mL
8.0 mL
20.0
10.0
5.0
2.5
1.25
b
b
b
b
b
Any solution for injection that has been stored for more than 24 hours as well as
any unused solution lor injection should be discarded. For sale disosal ol the
reconstituted solution, see SPECIAL HANDLING INSTRUCTIONS
SUPPLEMENTAL PRODUCT INFORMATION
ABMhSTRAT0h
Dosing Considerations
Unit doses recommended for XEOMIN
are not interchangeable with those for other preparations of

Botulinum toxin.
XEOMIN
may only be used by physicians with suitable qualications and proven experience in the application of Botulinum
toxin and in the use of the necessary equipment, e.g. EMG (electromyography).
Reconstituted XEOMIN
is intended for intramuscular injection. After reconstitution, XEOMIN
should be used for only one

injection session and for only one patient.
The minimal injection intervals and the maximum doses ol XE0Mh
should be as recommended for the specic indica-

tion.
The otimum dosaqe and number ol injection sites in the treated muscle should be determined by the hysician individually
for each patient. A titration of the dose should be performed.
A decrease or increase in the XEOMIN
dose is possible by administering a smaller or larger injection volume. Initial dosing

should begin at the lowest recommended dose for the specic indication and be cautiously titrated within the recommended
range for optimal patient outcome.
If no treatment effect occurs within one month after the initial injection, the following measures should be taken:
Clinical verilcation ol the neurotoxin ellect on the injected muscle. e.q. an electromyoqrahic investiqation in a secialised
facility.
Analysis ol the reason lor nonresonse, e.q. oor isolation ol the muscles intended to be injected, too low dose, oor
injection technique, xed contracture, too weak antagonist, possible development of antibodies.
Review ol Botulinum neurotoxin tye A treatment as an adequate theray.
l no adverse reactions have occurred durinq the initial treatment, an additional course ol treatment can be
performed under the following conditions: 1) dose adjustment with regard to analysis of the most recent therapy failure, 2)
EMG-guidance, 3) the recommended minimum interval between the initial and repeat treatment is followed
A treatmentnaive atient should be reqarded as a rimary nonresonder in cases ol lrst injection lailure. t has
not been investigated whether secondary non-response due to the development of antibodies is less frequent under
XEOMIN
therapy than under treatment with conventional preparations containing the Botulinum toxin type A
complex. In cases of non-response, alternative therapies should be considered.
XEOMIN
has not been studied in the paediatric population and is therefore not recommended in the paediatric age group
until further data become available.
Prior to administering XEOMIN
, the physician must familiarise himself/herself with the patients anatomy and any alterations
to the anatomy due to prior surgical procedures. Extra caution is required when injecting at sites close to sensitive structures
such as the carotid artery and lunq aices. There were no clinical data available in lonqterm reeat dose treatment and in treat-
mentnaive atients lor cervical dystonia and bleharosasm. however, there is inlormation available with reeat dose treat-
ment and in treatment-naive patients for post-stroke spasticity of the upper limb.Clinical effects of XEOMIN
may increase or
decrease with repeated injections. Possible reasons for change in clinical effect are different techniques of reconstitution, the
chosen injection intervals, the injected muscles and marginally varying toxin activity resulting from the biological testing pro-
cedure employed or secondary non-response. Previously akinetic or sedentary patients should be reminded to gradually re-
sume activities following the injection of XEOMIN
. XEOMIN
contains albumin, a derivative of human blood. Standard meas-

ures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include careful
selection of donors, screening of individual donations and plasma pools for specic markers of infection and
the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medi-
cinal products prepared from human blood or plasma are administered, the possibility of transmitting infective
aqents cannot be totally excluded. This also alies to unknown or emerqinq viruses and other athoqens. There are
no reports of viral transmissions with albumin manufactured to European Pharmacopoeia specications by
established processes.
Immune
The risks lor develoment ol neutrali/inq antibodies to Botulinum toxins are related to hiqh dosaqe, too lrequent injections,
young age at disease onset, and higher total dosage received of Botulinum toxin. Antibody development may lead to treat-
ment resistance (See B0SAE AhB ABMhSTRAT0h).
Less Common Clinical Trial Adverse Drug Reactions (<1%)
Cervical Dystonia: eye pain, diarrhoea, dry mouth, vomiting, colitis, asthenia, injection site inammation, injection site tender-
ness, skeletal pain, myalgia, headache, tremor, dysphonia, skin rash, erythema, pruritus, sweating increased.
Blepharospasm: conjunctivitis, dry mouth, inicted injury, muscle weakness, paraesthesia, headache, skin rash.
Post-stroke Spasticity ol the ber Limb. dry mouth, eriheral oedema, myalqia, couqh.
Abnormal Hematologic and Clinical Chemistry Findings
In all clinical trials, there were no ndings indicative of underlying pathological changes as a result of trial medication, both
with regard to the incidence of abnormal hematologic and clinical chemistry values and with regard to the mean change in
laboratory values for either treatment group.
Post-Market Adverse Drug Reactions
The lollowinq adverse reactions have been reorted since XE0Mh
has been marketed: eye swelling, eyelid

edema, madarosis, vision blurred; injection site reactions; asthenia, fatigue; dysphagia, nausea, abdominal disten-
sion; hypersensitivity including allergic dermatitis, skin rash, erythema, drug eruptions, lymphadenopathy, alopecia;
dysphonia, cough, dyspnoea, asthma; herpes zoster; muscular weakness, muscle spasm, myalgia, trismus;
dysarthria, headache, somnolence; cardiovascular insufciency, circulatory collapse; abnormal dreams.
Side effects related to spread of toxin distant from the site of administration have been reported very rarely
(exaggerated muscle weakness, dysphagia, and aspiration pneumonitis with fatal outcome in some cases).
Byshaqia has been reorted lollowinq injection to sites other than the cervical musculature. The lollowinq other adverse
events have been reported following administration of conventional Botulinum toxin type A complex: dysarthria, abdominal
pain, hyperhidrosis, anorexia, hypoacusis, tinnitus, radiculopathy, and syncope.
There have been rare reorts ol undesirable ellects related to the cardiovascular system, such as arrhythmia
and myocardial infarction, some with fatal outcomes. It remains unclear whether these deaths were induced by
conventional preparations containing the Botulinum toxin type A complex or whether these were caused by
pre-existing cardiovascular disease. Serious and/or immediate hypersensitivity reactions have been rarely reported, includ-
ing anaphylaxis, serum sickness, urticaria, soft tissue oedema, and dyspnoea. Some of these reactions have been reported
following the use of conventional Botulinum toxin type A complex either alone or in combination with other agents known
to cause similar reactions.
0T interval rolonqation has been reorted in 2 out ol 8GG atients lollowinq administration ol XE0Mh
in clin-
ical studies with blepharospasm and cervical dystonia patients. However, these ndings were not considered
clinically relevant in the opinion of the treating cardiologist and the exact relationship of these events to XEOMIN
is un-
known.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably
estimate their frequency or establish a causal relationship to drug exposure.
OTHER INTERACTIONS
Drug-Food Interactions
Interactions with food are not relevant.
Drug-Herb Interactions
Interactions with herbal products have not been established.
Drug-Laboratory Interactions
Interactions with results of laboratory tests have not been established.
Drug-Lifestyle Interactions
XEOMIN
has minor or moderate inNuence on the ability to drive and use machines. This can be comounded by some ol
the therapeutic and/or adverse effects of XEOMIN
, which may also interfere with the ability to drive and operate machinery.
Consequently affected persons should avoid these tasks until their faculties are fully recovered.
OVERDOSAGE:
Increased doses of Botulinum neurotoxin type A may result in pronounced neuromuscular paralysis distant from the injec-
tion site. Symtoms ol overdose are not immediately aarent ostinjection. These tyically occur 12 to 72 hours alter
exposure. Signs of overdose may include general weakness, ptosis, diplopia, swallowing and speech difculties, or paralysis
of the respiratory muscles resulting in an aspiration pneumonia.
In case of an overdose, the patient must be monitored medically for several days. If signs of intoxication appear,
hospitalisation with general supportive measures is necessary. Intubation and assisted ventilation will become
necessary until improvement if paralysis of the respiratory muscles occurs.
The lethal amount ol crystalline Botulinum toxin Tye A lor a 7O kq human is calculated to be aroximately O.OO to O.15
q alied intravenously or intramuscularly, and 7O q alied orally. A vial with 1OO bnits XE0Mh
contains 0.6 ng Botu-

linum heurotoxin Tye A, i.e. less than 1/1OO ol the estimated human lethal dose lollowinq intravenous or intramuscular
application.
XEOMIN
is a registered trademark of Merz GmbH.

Full roduct monoqrah available on request by contactinq Mer/ Fharma Canada Ltd at 1877811G87O.

MERZ PHARMA CANADA
22 nAugust 2011
P
sychiatrist Dr. Steven Cohen has been
on missions with Mdecins Sans
Frontires, or Doctors Without
Borders, in both Chad and Sudan. In
Darfur, Dr. Cohen helped develop a basic
medication management program to train
local physicians how to diagnose and treat
severe mental illness, focusing mainly on
schizophrenia. In Chad he worked with a
team of nine Sudanese refugee counselors
and 26 local community health workers. Together, his mental health
treatment group had about 500 patient encounters per month.
Q:
Has there been a case that particularly struck
you in your travels?
A:
While I was in Sudan I saw one fellow with schiz-
ophrenia who had unfortunately become psychot-
ic. In a violent rage while very ill he killed his brother.
The family and the community were fairly sophisticated.
They recognized that while he did this horrific act, he
was not thinking clearly, and did not know right from
wrong. They continued to support him, but realized that
they had to keep him from hurting others. He was
chained to a big log, so that he couldnt walk very quick-
ly. It seemed to be barbaric and quite inhumane, but
over time and after many discussion with local care
workers, I got a sense that it was actually a tenable, if far
from ideal, short-term solution in that region.
We prescribed haloperiodol 0.5 mg twice daily and
eventually titrated him up to 1 mg twice a day, a remarkably
low dose, but enough to resolve this mans acute psychosis.
He improved quickly, over the span of a month or
two, and became well enough to take part in the family
business, take on familial responsibilities, and, at the
time that I left the region, was engaged to a woman and
planning a marriage.
Q:
So you get off the airplane in Chad. What hap-
pens then?
A:
When I went to Chad, it took about over two
weeks to get to that small camp where the MSF
project was located. I flew into the capital, NDjamena.
Theres a bus that picks you up and drives you to the
terminal even though you could probably walk it faster.
And then you walk out of the small terminal, its just a
sea of white Land Cruisers.
These vehicles are the hallmark of most of the
NGOs who are in that region. And, because nobody
else wants to be targeted as being part of an oil consor-
tium or somebody who has money, other groups start
using them. Quite despicably, even the military has, at
some points, used white Land Cruisers, as [the vehicle]
provides them some protection against being targeted.
This is not good for humanitarians, you can see.
Q:
What was it like in Sudan?
A:
There was, of course, a genocide in Darfur that
had started about 2003, leading to a large number
of people being killed, displaced within Sudan, and
fleeing to neighbouring countries, such as Chad.
There were ongoing acts of violence where villages
were razed and families decimatedwhole villages
would be burned down and women were systematical-
ly raped as an act of war. Men would have their live-
stock stolen or be beaten. It was not unusual to have
their teeth cracked. That was still going on but it was
going on a smaller scale than years before. It is hard to
treat stress-born illness in the context of an ongoing,
unstable, and dangerous conflict.
Q:
Did you see many PTSD patients?
A:
I thought that when I arrived in Chad and Sudan,
that there would be many people with PTSD,
maybe even an epidemic, but we didnt see that much of
it. By the time that I had arrived, the heart of the crisis
had been over for about three and a half to four years.
Many had navigated through that crisis phase and
were rebuilding their lives. Religious groups, sporting
activities, family occasionspeople found support and
meaning in them.
Q:
You were surprised by how few cases of PTSD
there were. Can you speculate as to why that
would be?
A:
I think its human resilience. People get better.
PTSD is a transient illness, in large part. The trau-
ma never leaves entirely, but with the passage of time
and the budding of new and healthy experiences, it
becomes less prominent. Ive never seen communities
as strong those among the Sudanese. It makes a world
of difference.
Dr. Steven Cohen is now a staff psychiatrist at the CAMH law
and mental health program in Toronto. He trained as a physician
at the University of Calgary and spoke with CHRONICLE
assistant editor Josh Long.
Whos making a difference near you?
Tell The Chronicle, so we can tell our readers.
Write us at health@chronicle.org
Psychiatry without borders
n In conversation Steven Cohen, a psychiatrist who volunteers for the group Doctors without Borders
Com
eve
Int
fea
Sig
tio
(T
On F
If the nineteenth century was the age of the editorial
chair, ours is the century of the psychiatrists couch..
Marshall McLuhan (1911-1980) Canadian communications
theorist and educator.
Dr. Steven Cohen Dr. Steven Cohen
oing,
udan,
TSD,
ch of
crisis
ears.
and
rting
t and
PTSD
that
etter.
trau-
time
es, it
nities
world
H law
sician
ICLE
you?
ders.
e.org
Introducing the greenChronicle
Coming soon: A bimonthly electronic supplement to The Chronicle with original multimedia content in
every issue. Optimized for iPad, and readable on your computer, e-reader and electronic device.
Interactive, real-time news, opinion and education in the CNS sciences, with two intriguing value-added
features: Its free. And no trees were harmed in the preparation of this journal.
Sign up for your free subscription now at www.chronicle.ca, and be among the first to receive the revolu-
tionary greenChronicle. And while youre at it, why not follow us on Twitter and Facebook?
Your device. Our content.
(This could be the ultimate word-association.)
On Facebook: Chron Neuropsych On Twitter: CNSChronicle
orial
ch..
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cator.
See prescribing summary on page xxx
References: 1. Cipralex Product Monograph, February 2010. Lundbeck Canada Inc.
2. Data on file. Lundbeck Canada Inc.
CIP-342-11E
Registered trademark of Lundbeck Canada Inc.
For more information, please refer to
the complete Cipralex Product Monograph.
Discover the Power of Cipralex
In Depression
and in GAD
Most common adverse events reported by patients treated with Cipralex
(escitalopram oxalate) for Major Depressive Disorder (MDD)

were mild and transient in nature and included: headache (15.8% vs. 16.4% placebo) and nausea (15.2% vs. 8.1% placebo). The most
common adverse events reported by patients treated with Cipralex for Generalized Anxiety Disorder (GAD) were mild and transient in
nature and included: headache (23.7% vs. 18.6% placebo), nausea (19.4% vs. 9.0% placebo) and insomnia (10.1% vs. 3.7% placebo).
Cipralex is indicated for the symptomatic relief of MDD. The efficacy of Cipralex in maintaining an antidepressant response, in patients with MDD who responded
during an 8-week, acute-treatment phase while taking Cipralex and were then observed for relapse during a period of up to 36 weeks, was demonstrated in a
placebo-controlled trial. Cipralex is indicated for the symptomatic relief of anxiety causing clinically significant distress in patients with GAD. The efficacy of
Cipralex in maintaining anxiolytic response for at least 6 months in patients with GAD was demonstrated in a long-term placebo-controlled trial (in patients who
had initially responded to Cipralex during a 12-week open-label phase). Physicians who elect to use Cipralex for extended periods should periodically
re-evaluate the usefulness of the drug for individual patients.
Cipralex should not be used in combination with an MAOI or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should
elapse after discontinuing Cipralex treatment before starting an MAOI. Cipralex should not be used in combination with the antipsychotic drug pimozide.
Cipralex is not indicated for use in patients under 18 years of age. In these patients, the use of SSRIs and other newer antidepressants may be associated with
behavioural and emotional changes, including an increased risk of suicidal ideation and behaviour over that of placebo.
In both pediatrics and adults, there have been reports of severe agitation-type adverse events coupled with self-harm and harm to others with SSRIs and
other newer antidepressants. The agitation-type events include:
akathisia, agitation, emotional lability, hostility, aggression,
depersonalization. In some cases, the events occurred within
several weeks of starting treatment. Patients currently taking
Cipralex should NOT be discontinued abruptly, due to risk
of discontinuation symptoms. A gradual reduction in the dose
is recommended.
See prescribing summary on page 17

The Chronicle of Neurology + Psychiatry Aug 30 2011

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by Josh Long,

Assistant Editor, The Chronicle

is not likely to be effective at a joint affected by a xed contracture.

. Therefore, the unit or U used to describe XEOMIN

activity are different from those used

activity are not interchangeable with other products.

(See product monograph for DOSAGE AND ADMINISTRATION).

is a registered trademark of Merz GmbH.

C.P. Pharmaceuticals International C.V.,

by paying up to 20% of the

Patient Assistance Plan

is indicated for the symptomatic relief of obsessive-compulsive disorder

(escitalopram oxalate) is contraindicated in patients with known hypersensitivity

in the third trimester. Interference with

and MAO inhibitors (including linezolid, an antibiotic which is a

(escitalopram oxalate) is not indicated for use in children under

should be discontinued if such events

tablets are made by:

is indicated in adults for the symptomatic management of:

as a treatment for focal spasticity has been studied in association with

is not likely to be effective at a joint affected by a xed contracture.

may only be used by physicians with suitable qualications and proven

. Therelore, the "unit" or "b"

activity are different from those used to describe

should be used with caution: in patients suffering from amyotrophic lateral

for the management of

should be used with caution if bleeding disorders of any type occur. It

injection into the orbicularis muscle can

during lactation is not recommended.

in children and it is therefore not currently

, active comparator or placebo). See

Number of Subjects (%)

with aminoglycosides, polymyxins,

dosing must be tailored

is injected using a suitable sterile needle (e.g.

solution is injected using a suitable

is usually injected into

more uniform coverage of the innervated areas

is reconstituted prior to use with sterile unpreserved sodium chloride 9 mg/

should not be used if the reconstituted solution (prepared as above) has

in the Reconstituted Solution

are not interchangeable with those for other preparations of

is intended for intramuscular injection. After reconstitution, XEOMIN

should be used for only one

should be as recommended for the specic indica-

dose is possible by administering a smaller or larger injection volume. Initial dosing

contains albumin, a derivative of human blood. Standard meas-

has been marketed: eye swelling, eyelid

contains 0.6 ng Botu-

is a registered trademark of Merz GmbH.

(escitalopram oxalate) for Major Depressive Disorder (MDD)

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