All five selective serotonin reuptake inhibitors currently available in the United States ( Table 1) inhibit the presynaptic reuptake of serotonin. Fluvoxamine and sertraline demonstrate a relative specificity for the serotonin uptake transporter, whereas venlafaxine, fluoxetine, and paroxetine also inhibit norepinephrine uptake. The proposed mechanism of antidepressant action is the enhancement of serotonergic neurotransmission, but other mechanisms have been proposed.
All selective serotonin reuptake inhibitors effectively treat depression and some lead to improvement of obsessive-compulsive disorder and bulimia nervosa. Selective serotonin reuptake inhibitors do not cause anticholinergic side-effects, cardiac conduction abnormalities, weight gain, or orthostatic hypotension. They are far safer than cyclic antidepressants when taken in overdose. The major side-effects are insomnia, gastrointestinal discomfort, sexual dysfunction, and headache. Lack of therapeutic response or development of side-effects with one selective serotonin reuptake inhibitor does not necessarily predict the same outcome with another.
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