Useful to group according to known actions on CNS monoaminergic systems (Table 200-1 Antidepressants). The selective serotonin reuptake inhibitors (SSRIs) have predominant effects on serotonergic neurotransmission, also reflected in side-effect profile. The TCAs, or tricyclic ADs, affect noradrenergic and, to a lesser extent, serotonergic neurotransmission but also have anticholinergic and antihistaminic effects. Venlafaxine, desvenlafaxine, duloxetine, mirtazapine, vilazodone, vortioxetine, and levomilnacipran have mixed noradrenergic and serotonergic effects. Bupropion is a novel AD that enhances noradrenergic function. Trazodone and amoxapine have mixed effects on serotonin receptors and on other neurotransmitter systems. The monoamine oxidase inhibitors (MAOIs) inhibit monoamine oxidase, the primary enzyme responsible for the degradation of monoamines in the synaptic cleft.

ADs are effective against major depression, particularly when neurovegetative symptoms and signs are present. Despite the widespread use of SSRIs, there is no convincing evidence that they are more efficacious than TCAs, although their safety profile in overdose is more favorable than that of the TCAs. ADs are also useful in treatment of panic disorder, posttraumatic stress disorder, chronic pain syndromes, and generalized anxiety disorder. The TCA clomipramine and the SSRIs successfully treat obsessive-compulsive disorder.

All ADs require at least 2 weeks at a therapeutic dose before clinical improvement is observed. All ADs also have the potential to trigger a manic episode or rapid cycling when given to a pt with bipolar disorder. The MAOIs must not be prescribed concurrently with other ADs or with narcotics, as potentially fatal reactions may occur. “Withdrawal syndromes” usually consisting of malaise can occur when ADs are stopped abruptly.