SSRIs, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have all been reported to be associated with a reduction in sexual interest in some patients. Jacobsen78 reported reduced libido in 21% of 160 patients treated with fluoxetine. Ten percent of his series reported decrease in libido alone, and a further 11% reported decrease in libido and decreased sexual response. A recent analysis of pooled data from several placebo-controlled trials involving nefazodone, imipramine and fluoxetine provides a useful guide for all aspects of sexual dysfunction to be described here and in the following paragraphs.79 Decreased libido was found in 0.5% of placebo-treated patients, 0.7% of nefazodone-treated patients, 1.6% of imipramine-treated patients and 2.2% of fluoxetine treated patients. The rate of decreased libido for fluoxetine treatment was significantly greater than for placebo. The differences observed between nefazodone and fluoxetine may depend upon the 5-HT2C receptor blocking effects of the former, or the more potent reuptake-blocking effects of the latter. These rates are low, reflecting the self-report design of the studies included. MAOIs have also been associated with a decrease in libido in some patients.80
The mechanisms by which antidepressant drugs might cause reduction in sexual desire are not established. Dopamine has been demonstrated to be involved in sexual interest and enhanced serotonergic function in the CNS could result in diminished dopaminergic effects causing decreased libido. Some cholinergic agonists such as bethanechol have been reported to reverse the loss of sexual desire associated with TCAs such as amitriptyline,81 underlining the possible importance of other neurotransmitter systems in mediating arousal.
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