• Antidepressants (mood-elevating drugs) are used for treatment of psychic
There are two main types of depression:
• Neurotic (reactive) depression which is precipitated by external factors as failure in
examination or business, death of a loved person, divorce. The individual blames the
situation rather than himself. This type of depression responds well to moral and social
support and does not require treatment with antidepressant drugs.
• Psychic (endogenous) depression in which the exact cause is unknown and the
patient has marked retardation in thoughts, slow movements and speech, high sense of
guilt, reduced appetite, weight loss, nightmares and suicidal tendency. Psychic
depression may occur in recurrent episodes (unipolar depression) or alternating with
manic episodes (manic-depressive psychosis or bipolar affective disorder).
• The etiology of endogenous depression is unknown. However, after the introduction
of reserpine in clinical practice in early 1950s, it was noted that the drug caused
psychic depression due to depletion of the central stores of biogenic amines
(serotonin and norepinephrine).
• It was concluded that psychic depression is associated with decreased central
biogenic amines (amine theory of depression). Also, all the available antidepressant
drugs act mainly by increasing the concentration of serotonin, norepinephrine or
both in the CNS.
• Increased central serotonin concentration causes mood elevation, while increased
central norepinephrine concentration increases physical activity.
Classification and Mechanism of action:
1. Tricyclic antidepressants (TCAs):
• Imipramine, amitriptyline.
• TCAs act by inhibiting active neuronal uptake of the biogenic amines (5-HT and
NE) by the nerve terminals due to competition for the same uptake pathway. This
allows the biogenic amines to act for a longer duration at their receptor sites.
2. Monoamine oxidase (MAO) inhibitors:
• Phenelzine, tranylcypromine.
• They act by inhibiting MAO enzyme preventing degradation of the biogenic amines
(5-HT and NE) and therefore increasing their duration of action.
3. Selective serotonin reuptake inhibitors (SSRIs):
• Fluoxetine (Prozac) and paroxetine (Seroxate).
• They selectively inhibit 5-HT uptake by the nerve terminals.
• TCAs and MAO inhibitors are the first antidepressants used, while SSRIs are recent
• SSRIs have the same efficacy of the older agents, however, they are more safe and
better tolerated and therefore they are most commonly used now.
• All antidepressant drugs have delayed onset of action (after 2-3 weeks of continued
• Stopping treatment should be gradual after prolonged use. Abrupt stopping leads to
aggravation of the symptoms.
• Antidepressant action: antidepressant drugs elevate the mood of
depressed patient but have no effect on the mood of normal
• Anticholinergic (atropine-like) action: TCAs block both central and
peripheral muscarinic receptors.
• Cardiovascular system: TCAs cause postural hypotension due to
block of peripheral α1–adrenergic receptors.
Therapeutic uses of antidepressants:
• Endogenous (psychic) depression.
• Panic (phobic) disorders (SSRIs).
• Obsessive-compulsive disorder (SSRIs).
• Nocturnal enuresis (particularly TCAs given at bedtime).
• Chronic pain (TCAs).
• Hyperactivity disorders in children (attention-deficit syndrome).
• Bulimia nervosa (episodes of uncontrolled eating followed by self-
• Sedation, drowsiness and confusion (with TCAs).
• Atropine-like action: dry mouth, blurred vision, tachycardia, urine
retention, constipation (with TCAs which are contraindicated in
benign prostatic hyperplasia and glaucoma).
• Postural hypotension (with TCAs).
• Weight gain and sexual disturbances (with TCAs and MAO
• Nausea, vomiting, anxiety, insomnia (with SSRIs at the initiation of
treatment and disappear spontaneously with continued therapy).
Drug interactions of antidepressants:
• MAO inhibitors + indirect sympathomimetics (amphetamine, ephedrine) leads to
• MAO inhibitors + tyramine-rich food (tyramine is an indirect sympathomimetic)
leads to hypertensive crisis (cheese reaction).
• MAO inhibitors + SSRIs leads to marked increase in 5-HT at the receptor site
producing muscle rigidity, hyperthermia, depression of vital signs which may be
fatal (serotonin syndrome). Therefore, this combination is not recommended in
treatment of psychic depression.
• MAO inhibitors + TCAs leads to hypertensive crisis and this combination is
disapproved in treatment of psychic depression.