Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical

Psychopharmacology

ISSN: 1017-7833 (Print) 1302-9657 (Online) Journal homepage: http://www.tandfonline.com/loi/tbcp20

A Serious Risk: Excessive and Inappropriate

Antipsychotic Prescribing

Mesut Cetin M.D.

To cite this article: Mesut Cetin M.D. (2014) A Serious Risk: Excessive and Inappropriate
Antipsychotic Prescribing, Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology,
24:1, 1-4

To link to this article: http://dx.doi.org/10.5455/bcp.20140314014626

© 2014 Taylor and Francis Group, LLC

Published online: 08 Nov 2016.

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Editorial DOI: 10.5455/bcp.20140314014626

A Serious Risk: Excessive and In recent years, recommendations such as those

Inappropriate Antipsychotic from NICE, CANMAT guidelines and Harvard and
Prescribing Texas Treatment Algorithm Projects as well as
guidelines published by professional organizations
Mesut Cetin such as the American Psychiatric Association,
American Diabetes Association, International
Bulletin of Clinical Psychopharmacology 2014;24(1):1-4 Diabetes Federation, American Heart Association
and American Geriatrics Society have emphasized
Although antipsychotics are known to be capable the necessity of following up patients who use
of effectively treating many mental disorders when antipsychotics for clinical safety related to
used appropriately, misuse and/or purposeless use neuromuscular, metabolic and cardiovascular side
of these agents, especially in the long term, may effects. In addition, these guidelines have
place the patients at serious risk1-7. As a matter of recommended investigation of genetic illness
fact, a comprehensive study by Khan, et al. revealing potential and implementation of some tests such as
the association of psychotropic agents with increased body weight, waist circumference or BMI, blood
mortality has been published recently1. This study pressure, pulse, fasting blood glucose, lipid profile
covered in detail 92,542 patients recruited for trials (triglycerides, LDL and HDL cholesterol levels etc.)
sponsored by pharmaceutical companies for FDA even before starting an antipsychotic medication.
indication approval programs, in particular for Studies have demonstrated that the frequency
treatment of schizophrenia, depression, bipolar of use of two or more antipsychotics (antipsychotic
disorder and anxiety, or for FDA approval for polypharmacy) is 4-35% amongst outpatients and
maintenance treatment of attention deficit and 30-50% amongst hospitalized patients. Although
hyperactivity disorder. This population polypharmacy could provide benefit for a limited
corresponded to 47 acute, placebo controlled number of patients if applied rationally, casual
psychopharmacology trials and safety extension and/or irrational use of polypharmacy may lead to
trials conducted between 1990 and 2011. In this very serious side effects, even to death, and a
group of patients, death risk was found to be pharmacoeconomic burden as well. This relatively
significantly higher and associated with the high frequency of polypharmacy in psychiatric
24
psychiatric diagnosis (χ = 1.760, p<.001). When practice may be based on a number of factors such
compared with the overall adult population, the as the chronic nature of some mental disorders,
highest mortality ratios were found to be with resistance to pharmacological treatment, multiple
schizophrenia (3.8 fold increase), depression (3.15 etiologies in many cases, high frequency of
fold increase) and bipolar disorder (3.0 fold increase), co-morbidity, substance misuse and
respectively. The total number of suicides of 109 noncompliance to treatment. In addition, the
corresponded to 41.1% of all deaths (n=265). Modern evidence for polypharmacy is limited and the risks
psychotropic drugs such as atypical antipsychotics, associated with drug interactions, noncompliance
selective serotonin reuptake inhibitors and selective and erroneous use of medications increase because
serotonin-norepinephrine reuptake inhibitors did of irrational polypharmacy. As a general rule,
not increase the risk of mortality upon exposure for a polypharmacy should only be considered after
period of 3-4 months. Moreover, appropriate use of three consecutive failures of monotherapy with
modern psychotropic agents decreased the mortality clozapine used in one of those attempts. Switching
risk associated with the leading complications of from one medication to the next should be made
mental disorders such as suicidal ideation and using stepwise cross-titration, if applicable.
tobacco or substance use by 25-70%1. Behavioral and psychological symptoms of

Klinik Psikofarmakoloji Bülteni, Cilt: 24, Sayı: 1, 2014 / Bulletin of Clinical Psychopharmacology, Vol: 24, N.: 1, 2014 - www.psikofarmakoloji.org 1
A Serious Risk: Excessive and inappropriate antipsychotic prescribing

Table 1: IMS Health moving annual term data for antipsychotic sales in units and value7
Units Units Units Units Units Units Units Units Units Units Units Units Units
Oct/12 Nov/12 Dec/12 Jan/13 Feb/13 Mar/13 Apr/13 May/13 Jun/13 Jul/13 Aug/13 Sep/13 Oct/13

NO5A1 ATYPICAL ANTIPSYCHOTICS 812.114 951.573 832.330 870.051 814.731 912.315 928.602 944.845 854.838 880.924 808.473 917.458 907.243

TL TL TL TL TL TL TL TL TL TL TL TL TL
Oct/12 Nov/12 Dec/12 Jan/13 Feb/13 Mar/13 Apr/13 May/13 Jun/13 Jul/13 Aug/13 Sep/13 Oct/13

NO5A1 ATYPICAL ANTIPSYCHOTICS 23.816.508 27.153.405 24.455.912 24.866.382 23.301.372 26.552.191 26.486.598 27.789.417 25.559.042 25.873.394 23.889.066 27.083.720 26.355.018

dementia are defined as non-cognitive symptoms, increasing in Turkey, where almost all active
including behaviors such as agitation or hostility, pharmaceutical ingredients are imported. For
anxiety, volatility, depression, lack of interest and instance, the total national health spending of
even psychosis. Antipsychotics should only be used 57,911 million TL (37,493 million USD) in 2009, has
for those patients for whom a non-pharmacological reached 76,278 million TL (42,332 million USD),
treatment is not efficacious or who have become which corresponds to an increase of 131.71%,
harmful to themselves and others. Relatively high despite state discounts. The ratio of national health
susceptibility to extrapyramidal symptoms, spending to gross domestic product was 6.1% in
depleted drug metabolism and elevated use of other 2009 and 5.4% in 20125.
medications for comorbid physical illnesses when In particular antipsychotic use, according to IMS
compared to younger populations should limit the year-to-date data, has increased, with total sales of
use of antipsychotics in the elderly population6. SGAs in October 2012 of 23,816,508 TL and in
Another highly prevalent misapplication is the October 2013 of 26,335,018 TL (a 110% increase) 5
empirical use of second generation antipsychotics (Table 1, 2).
(SGAs) such as quetiapine for the treatment of sleep Moreover, trespassing beyond the boundaries
disorders (primary or secondary to a psychiatric or between specializations is frequent. Antipsychotic
physical condition) even in psychologically non- prescribing (initiation or maintenance treatment)
symptomatic patients. This use is irrational because habits of general practitioners and some specialists
there is a lack of evidence for the efficacy of SGAs are shown in the table below (Table 3). Of all
such as quetiapine in sleep disorders and these antipsychotic prescriptions, 55.68% were produced
medications may cause more harm than benefit by psychiatrists whereas 66.39% of initial
because of their metabolic side effects1. antipsychotic prescriptions (initiation treatment)
Recent studies have demonstrated that the were issued by psychiatrists.
pediatric use of antipsychotics in the USA for For the reasons presented above, the ABIM
conditions other than schizophrenia has increased Foundation has announced a 5 item advice letter
almost 3 folds in the last 10-15 years. Evidence for about the use of antipsychotics2.
the safety (weight gain, metabolic side effects,
relatively high cardiovascular risks compared to 1. Do not prescribe antipsychotics for any
adults) and efficacy of antipsychotics in children indication without a prior appropriate evaluation
and adolescents is scant1. and continuous follow up.
In Turkey, the propensity for use of antipsychotics 2. Do not routinely prescribe two or more
in particular and for use of medications in general antipsychotics at a time.
seems to be similar to the USA and other parts of the 3. Do not use antipsychotics as first-line treatment
world. Indeed, the total expenditure in Turkey for in elderly patients for the treatment of behavioral
drugs in 2001 was 3,213 million Turkish Liras and and psychological symptoms.
15,726 million Turkish Liras in 2013, corresponding 4. Do not use antipsychotics as first-line treatment
to an almost 5 fold of increase5 (Table 1). in elderly patients for the treatment of sleep
Health spending has been progressively disorders.

2 Klinik Psikofarmakoloji Bülteni, Cilt: 24, Sayı: 1, 2014 / Bulletin of Clinical Psychopharmacology, Vol: 24, N.: 1, 2014 - www.psikofarmakoloji.org
 Cetin M

Tab­le 2: IMS Health data for antipsychotic sales: trends in units Tab­
le 3: IMS Health data for distribution of antipsychotic
and value for the last 3 years prescriptions amongst specializations for the last 3 years (7).
Row Labels Sum of 2011 Sum of 2012 Sum of 2013 Row Labels Sum of 2011 Sum of 2012 Sum of 2013
QUETIAPINE 31.63% 32.57% 32.79% PSYCHIATRY 60.47% 58.56% 55.68%
SEROQUEL 9.66% 9.51% 9.92% FAMILY PRACTICE 24.34% 29.71% 32.58%
SEROQUEL XR 6.09% 6.32% 5.58% NEUROOLGY 13.76% 10.23% 10.53%
GYREX 3.33% 3.58% 4.70% INTERNAL MEDICINE 0.91% 0.96% 1.03%
CEDRINA 3.71% 3.87% 3.84% SURGERY 0.09% 0.23% 0.06%
KETILEPT 2.81% 3.43% 2.45% UROLOGY 0.08% 0.00% 0.05%
KETYA 2.43% 2.58% 2.22% GYNECOLOGY 0.06% 0.11% 0.03%
QUET 2.82% 1.74% 1.95% CARDIOLOGY 0.04% 0.06% 0.02%
SEREX 0.79% 1.12% 0.93% RESPIRATORY DISEASES 0.06% 0.06% 0.02%
QUELEPT 0.00% 0.20% 0.77% INFECTIOUS DISESASES 0.06% 0.01% 0.00%
SEQUA 0.00% 0.22% 0.38% DERMATOLOGY 0.03% 0.00% 0.00%
KETINEL 0,00% 0,00% 0,07% PEDIATRICS 0.06% 0.00% 0.00%
OLANZAPINE 17.46% 16.54% 15.98% PHYSICAL MEDICINE 0.02% 0.03% 0.00%
REXAPIN 6.81% 6.07% 5.63% OTORHYNOLARYNGOLOGY 0.00% 0.02% 0.00%
ZYPREXA 5.83% 5.55% 4.82% ORTHOPEDIA 0.02% 0.02% 0.00%
OZAPRIN 1.03% 0.62% 1.20%
ELYNZA 1.28% 1.71% 1.03% Grand Total 100.00% 100.00% 100.00%
OLFREX 0,42% 0,46% 1,01%
OFERTA 0.37% 0.76% 0.81%
OLAXINN 1.16% 0.85% 0.49%
OLNEGIS 0.00% 0.00% 0.47%
ZYZAPIN 0.46% 0.30% 0.31% 5. Do not use antipsychotics as first-line treatment
OLLAFAX 0.08% 0.09% 0.12%
PINOLZA 0.00% 0.00% 0.05% in children and adolescent patients for
ZOLAPINE 0.00% 0.05% 0.02%
ZOPHIX 0.01% 0.08% 0.00% conditions other than psychotic disorders.
RISPERIDONE 16.88% 17.16% 15.16%
RISPERDAL 7.68% 7.80% 7.53%
RILEPTID 3.91% 3.55% 2.48%
RISPERDAL CONSTA 3.36% 3.13% 2.45% As a result, there is a consensus on the necessity
RIXPER 0.97% 1.86% 2.43%
RICUS 0.21% 0.28% 0.20% for careful use and selection of antipsychotics, as
PERILIFE 0.53% 0.31% 0.08%
RESTELA 0.00% 0.07% 0.00% well as consideration of supporting psychosocial
RISFAMED 0.00% 0.06% 0.00%
RISPERDAL QUICKLET 0.11% 0.06% 0.00% interventions additional to antipsychotic treatment.
RIXOL 0.12% 0.05% 0.00%
ARIPIPRAZOLE 7.05% 7.43% 10.63% Antipsychotic treatment should be initiated very
ABILIFY 5.30% 4.60% 3.75%
ABIZOL 1.75% 1.95% 2.82% carefully only to hose who really need an
ARIPA 0.00% 0.55% 1.68%
IGNIS 0.00% 0.01% 1.05%
antipsychotic. The minimum effective dose should
ZOLERIP 0.00% 0.32% 0.68% be selected and the shortest available treatment
CUREXOL 0.00% 0.00% 0.64%
SULPIRIDE
MERESA
6.16% 5.78% 4.94%
3.10% 3.09% 2.59%
plan should be followed. Additional to the acute
SULPIR 2.65% 2.49% 2.06% treatment planning, a sufficiently timed
DOGMATIL 0.40% 0.20% 0.30%
ZEPRID 0.01% 0.00% 0.00% maintenance treatment should be designed in
HALOPERIDOL 4.21% 4.29% 3.45%
NORODOL 4.21% 4.29% 3.31% consideration of previous treatment experience,
NORODOL DEKANOAT 0.00% 0.00% 0.14%
TRIFLUOPERAZINE 2.29% 2.82% 2.98% attitudes and choices of the patient. A few simple
STILIZAN 2.29% 2.82% 2.98%
PALIPERIDONE 3.09% 2.56% 2.69% questions about indications, treatment goals, target
INVEGA 3.09% 2.56% 2.69%
CLOZAPINE 1.55% 2.03% 2.47% patients, dosing and duration of treatment should
LEPONEX 1.12% 1.40% 1.87%
CLONEX 0.43% 0.63% 0.60% be asked to prevent purposeless use of
AMISULPRIDE 2,85% 2,58% 2,26%
SOLIAN 2.82% 2.58% 2.24% antipsychotics, associated health risks for patients
PAXIPRID 0.03% 0.00% 0.01%
CHLORPROMAZINE 2.13% 2.13% 2.12% and pharmacoeconomic losses both for the nation
LARGACTIL 2.13% 2.13% 2.12%
ZUCLOPENTHIXOL 2.17% 2.05% 1.74%
and for patients.
CLOPIXOL 2.17% 2.05% 1.74%
PALIPERIDONE PALMITATE 0.00% 0.00% 1.09%
XEPLION 0.00% 0.00% 1.09%
Mesut Cetin, M.D., Professor of Psychiatry, Department
FLUPENTIXOL 0.70% 0.80% 0.59%
FLUANXOL 0.70% 0.80% 0.59% of Psychiatry, GATA Haydarpasa Training Hospital,
PIMOZIDE 0.67% 0.44% 0.44%
NOROFREN 0.67% 0.44% 0.44% Istanbul - Turkey
ZIPRASIDONE 0.76% 0.67% 0.44%
ZELDOX 0.76% 0.67% 0.44%
FLUPHENAZINE 0.29% 0.15% 0.19%
PROLIXIN 0.29% 0.15% 0.19% Correspondence Address: Mesut Cetin, M.D., Professor
ACEPROMAZINE 0.11% 0.00% 0.01%
PLEGICIL 0.11% 0.00% 0.01% of Psychiatry, Department of Psychiatry, GATA Haydarpasa
MESORIDAZINE 0.02% 0.00% 0.00%
LIDANIL WAN 0.02% 0.00% 0.00% Training Hospital, Istanbul - Turkey
Grand Total 100.00% 100.00% 100.00% Email address: mesutcetin@yahoo.com

Klinik Psikofarmakoloji Bülteni, Cilt: 24, Sayı: 1, 2014 / Bulletin of Clinical Psychopharmacology, Vol: 24, N.: 1, 2014 - www.psikofarmakoloji.org 3
A Serious Risk: Excessive and inappropriate antipsychotic prescribing
References:
1. Khan A Faucett J, Morrison S, Brown WA Comparative
mortality risk in adult patients with schizophrenia,
depression, bipolar disorder, anxiety disorders, and
attention-deficit/hyperactivity disorder participating
in psychopharmacology clinical trials. JAMA Psychiatry.
2013;70(10):1091-9. [CrossRef]
2. American Psychiatric Association. Choosing Wisely. http://
www.psychiatry.org/choosingwisely Accessed November
22, 2013. http://www.psychiatry.org/choosingwisely.
3. Olfson M, Blanco C, Wang S, Laje G, Correll CU. National
trends in the mental health care of children, adolescents,
and adults by office-based physicians. JAMA Psychiatry.
2014;71(1):81-90. [CrossRef]
4 Klinik Psikofarmakoloji Bülteni, Cilt: 24, Sayı: 1, 2014 / Bulletin of Clinical Psychopharmacology, Vol: 24, N.: 1, 2014 - www.psikofarmakoloji.org
4. Declercq T, Petrovic M, Azermai M, Vander Stichele R, De
Sutter AI, van Driel ML, Christiaens T.Withdrawal versus
continuation of chronic antipsychotic drugs for behavioural
and psychological symptoms in older people with dementia.
Cochrane Database Syst Rev. 2013;3:CD007726. doi:
10.1002/14651858.CD007726.pub2.
5. 10 October 2013 Turkish Statistical Enstitute News Bulletin/
Health and Social Protection http://www.tuik.gov.tr/
PreHaberBultenleri.do?id=15871. (Turkish)
6. Campanelli CM. American Geriatrics Society updated Beers
Criteria for potentially inappropriate medication use in older
adults. J Am Geriatr Soc Apr 2012;60(4):616-31. [CrossRef]
7. IMS Health Reports. February 2014.