Clinical (endogenous) depression, a heterogeneous biopsychologic disorder with genetic predisposition, can occur at any time in life, unrelated to obvious stressors. Treatment is required: approximately 15% of these patients commit suicide. Severe (major depression) and mild (dysthymic disorder) forms exist.
Findings that clinical depression may be related to an imbalance in endogenous amines (5HT or NE) in the CNS led to the amine hypothesis of etiology and spurred efforts to enhance synaptic action of these amines. Antidepressants are classified according to a presumed mechanism of action or chemical structure. TCAs and heterocyclics nonselectively inhibit both 5HT and NE. SSRIs enhance drugs metabolized via the cytochrome P450 pathway. MAOIs inhibit amine metabolism. Adverse effects (eg, mania, agitation, serotonin syndrome) and drug interactions (MAOIs used with TCAs or SSRIs) do occur.