Drugs Used in

Affective Disorders

MOOD/MOOD DISORDER
Sustained emotion

INCIDENCE
Higher in women than in men
Between ages 25 to 44

ETIOLOGY
Biogenic amine theory
Dysregulation theory
Family history

Range of emotions

Euthymia
Hypomania
Euphoria
Mania
Dysthymia
Dysphoria
Depression

Clinical features of major depression

One of the following must be present:

Depressed mood
Anhedonia (i.e., loss of interest or pleasure)
Plus four or more of the following:
Decreased or increased appetite
Unintentional weight loss or gain
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Feelings of worthlessness or excessive or inappropriate
guilt
Diminished ability to think or concentrate or
indecisiveness
Recurrent thoughts of death and/or suicidal ideation
Suicide attempt

Treatment
Psychotherapy
Pharmacotherapy
ECT

Treatment phases for depression

Treatment phase

Duration

Goal

Acute

6 weeks

Resolve
symptoms

Continuation

6-9 months

Prevent relapse

Maintenance

3-5 years of
lifelong

Prevent
recurrence in high
risk patients

Drug
selection/administration

All drugs are equally effective

Half the lowest dose
1-2 wks
4-6wks
Try onother class

Changing
antidepressant
2 wks
5 wks with fluoxetine

Clinical manifestations of serotonin

syndrome and serotonin withdrawal
syndrome

Classification of
dysfunction
Cognitivebehavorial
dysfunction
Autonomic
nervous system
dysfunction

Neuromuscular
dysfunction

Serotonin syndrome Serotonin

withdrawal
syndrome
Confusion
none
Hypomania
Agitation
Diarrhea Diaphoresis

Flu-like symptoms

Shivering

Dizziness

Fever

Light headedness

Changes in blood
pressure

Chills

Nausea and vomitting

Myoclonus
Hyperreflexia
Tremor
Death

Seizure

Sleep
disturbances
Lethargy
Myalgia sensory
disturbances (e.g.,
paresthesia)

Selective 5-HT uptake

inhibitors (SSRI)
1st line for depression
Actions similar in efficacy & time course
to TCA
Acute toxicity is less than that of MAOI or
TCA
Side-effects include nausea, insomnia &
sexual dysfunction.
dangerous 'serotonin reaction'
(hyperthermia, muscle rigidity, cardiovascular
collapse) can occur if given with MAOI.

Long half-lives

SSRI

Fluoxetine
Fluvoxamine
Nefazodone
Paroxetine
Sertraline
Trazodone
venlafaxine

SSRIs
Am bec of its stimulatory effect
Metabolize via cytochrome P450

SSRIs
Fluoxetine- bulimia
Most stimulatory
For depression with negative
symptoms

Paroxetine
Most sedating
Depression with anxiety and insomnia

Sertraline
Less stimulatory and less sedating

Tricyclic
antidepressants (TCA)
TCA are chemically related to
phenothiazine
2nd line of choice
Inhibit reuptake of serotonin and
norepinephrine
Important side-effects:

sedation (H1-block), postural hypotension (adrenoceptor block), dry mouth, blurred vision,
constipation (muscarinic block), occasionally
mania and convulsions.
Risk of ventricular dysrhythmias through
potassium channel block.

TCA

Amitriptylline
Amoxapine
Desipramine
Doxepin
Imipramine
Maprotiline
Nortriptyline
Protriptyline
timipramine

TCA

Imipramine
Very sedating,NOCTURNAL ENURESIS
Venlafaxine
Distinct from TCA
Less sedating
More GI upset
OC-CHLOMIPRAMINE

PM DOSAGE ALL- SEDATING ACTIVITY

4-6 WKS- FULL RESPOSE
1 WK ASSYMPTOMATIC RELIEF
ANTICHOLINERGIC SIDE EFFECTS

TCA

TCA USER
HEALTHY
NONSUICIDAL
REFRACTORY TO NEWER
DRUGS

TCA
BLOCKS REUPTAKE OF
SEROTONIN AND NE
BINDS TO ALPHA,HISTAMINE
AND CHOLINERGIC RECEPTORS

TCA
Important side-effects:

sedation (H1-block), postural

hypotension (-adrenoceptor
block), dry mouth, blurred vision,
constipation (muscarinic block),
occasionally mania and
convulsions.
Risk of ventricular dysrhythmias
through potassium channel block.

Tricyclic
Antidepressants (TCA)

TCAs are dangerous in acute

overdose,

causing confusion and mania, and

cardiac dysrhythmias.

liable to interact with other drugs

e.g. alcohol, anesthetics, hypotensive
drugs and NSAIDs

TCA should not be given with (MAOI).

Monoamine oxidase
inhibitors (MAOI)
Action is long lasting (weeks) due to
irreversible inhibition of MAO A & B.

Moclobemide has a short duration of action

3rd line of choice

Main side-effects:

postural hypotension (sympathetic block)

atropine-like effects (as with TCA);
weight gain
CNS stimulation
Serotonin syndrome
liver damage (rare). ISOCARBOXAZID

MAOI

ATYPICAL DEPRESSION
HYPERSOMNIA
AGITATION
ANXIETY

Monoamine oxidase
inhibitors (MAOI)
Phenelezine,Tranylcypromine,
Isocarboxazid
Rarely clinical due to serotonin
syndrome
hypertensive crisis- most common
(tyramine-rich foods)
3 -4 wks- do not discontinue
Insomnia effect not at pm

Side effects

Othostatic hypotension
Weight gain
Edema
Sexual dysfunction
Hepatocellular damageisocarboxacid

Other antidepressant
drugs

Heterogeneous group including,

trazodone, mirtazapine and

bupropion,venlafaxine,nefazodon
e

No common mechanism of action.

Act mainly as non-selective antagonists
at presynaptic receptors, possibly
enhancing amine release.
Delay in therapeutic response
Unwanted effects and acute toxicity vary
but are generally less than with TCA.

MANIA

Etiology

Genetics
Neurotransmitter level
GABA level
Calcium
G proteins
Psychosocial and physical
stressors

Symptoms of mania

Grandiose ideations or expansive self-esteem

Decreased need for sleep
Pressured speech
Racing thoughts or flight of ideas
Distractability
Psychomotor agitation
Engaging in dangerous, high-risk activities

LITHIUM
Mechanism of Action
?
alters intracellular second messengers:
adenyl cyclase-cyclic AMP system and
the G protein-coupled phosphoinositide
systems
(NE and serotonin)
alters ion channel function
alters metabolism of GABA

LITHIUM
Adverse effects
Narrow therapeutic index
Therapeutic range: 0.5-1.5mEq/L
Minor S/E: tremors, polyuria,
GI distress,
memory problems, acne,
weight gain
Long-term S/E: hypothyroidism
Toxic levels: ataxia, tremors, confusion,
coma, sinus arrest, death

LITHIUM
Baseline labs

Adverse effects

Thyroid
function
BUN/Crea

hypothyroidism

Electrolytes
(esp.sodium)
CBC

Renal
insufficiency
Dec. Na
leukocytosis

 Alternative moodstabilising drugs (e.g.

carbamazepine,
valproate,
gabapentin,clonazepam)

Summary

ANTICHOLINERGIC-TCA
CHLOMIPRAMINE-OC
IMIPRAMINE NOCTURNAL
MAOI- HYPERTENSIVE CRISIS
SEIZURE-SE OF BUPROPION