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 Prevent

lifelong 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
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.
SSRI

• Fluoxetine
• Fluvoxamine
• Nefazodone
• Paroxetine
• Sertraline
• Trazodone
• venlafaxine
SSRIs

• Am bec of its stimulatory effect

• Metabolize via cytochrome P450
SSRI’s
• Fluoxetine- bulimia
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 (α-adrenoceptor block), dry
mouth, blurred vision, constipation
(muscarinic block), occasionally mania
and convulsions.
TCA
• Amitriptylline
• Amoxapine
• Desipramine
• Doxepin
• Imipramine
• Maprotiline
• Nortriptyline
• Protriptyline
• timipramine
 TCA
• Imipramine
NOCTURNAL ENURESIS

• OC-CHLOMIPRAMINE

• PM DOSAGE ALL- SEDATING ACTIVITY

• 4-6 WKS- FULL RESPOSE
TCA

• BLOCKS REUPTAKE OF
SEROTONIN AND NE
• BINDS TO ALPHA,HISTAMINE
AND CHOLINERGIC RECEPTORS
 Cyclic Antidepressants
Tricyclic antidepressants—primary:
amitriptyline , doxepin , imipramine

Tricyclic antidepressants—secondary:
desipramine , nortriptyline ,
protriptyline

Tetracyclic antidepressants:
amoxapine , maprotiline
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
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
 Other antidepressant
drugs
• Heterogeneous group including,
trazodone, mirtazapine and
bupropion,venlafaxine,nefazodo
ne
• 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 hypothyroidism
function
BUN/Crea Renal
insufficiency
Electrolytes Dec. Na
(esp.sodium)
CBC leukocytosis
Alternative mood-
stabilising drugs

carbamazepine, valproate,
gabapentin, clonazepam
Summary

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