Antidepressant medications, also called antidepressive agents, are "mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (tricyclic antidepressant) also appear to act through brain catecholamine systems. A third group (second-generation antidepressant agents) is a diverse group of drugs including some that act specifically on serotonergic systems."
Mechanism of action
Depression may be due to the monoamine-deficiency hypothesis, which is a "deficiency in serotonin or norepinephrine neurotransmission in the brain."
Tricyclic antidepressants are "substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system."
Heterocyclic antidepressants include trazadone and bupropion, and more recently, mirtazapine and nefazadone which are based on trazadone
Second-generation antidepressants are a "structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake."
Monoamine oxidase inhibitors
The effectiveness is antidepressants depends on the severity of a patient's depression. This relationship may be due to thedeclining effect of placebo among more severely depressed patients.
|American Psychiatric Association classification of severity||Hamilton Depression Rating Scale (HDRS)||Number needed to treat||Clinical significance (NICE)|
|Mild to moderate||< 19||16||No|
|Severe||19 - 22||11||No|
|Very severe||> 22||4||Yes|
"The clinical response of our patients underscores the usefulness of mirtazapine in the treatment of the comorbid symptoms of weight loss, insomnia, and anxiety". 
Neuroleptic malignant syndrome
Recurrence of illness after discontinuation
The recurrence risk for depression or panic was shorter if antidepressants were discontinued over 7 days or less.
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