Psychotropic Medications

Psychotropic agents – particularly neuroleptics, tricyclics, and serotonin reuptake inhibitors (SRIs) – are associated with erectile, ejacula­ tory, orgasmic, and sexual desire difficulties. Mental illness and the management of mental disorders are a significant cause of sexual dysfunction in men. A recent population study reported a fivefold increase in odds of self-reported complete ED among men who used selected antidepressant therapy (principally selective SRIs and tricyclics) which exceeded the risk of ED attributed to depression symptoms or diagnosis. Antidepressant­associated ED is reported to occur with prevalence rates from 30 to 90%. Worsening or the initiation of sexual dysfunction has been reported with agents for all antidepressant classes, including mono-amine oxidase inhibitors, tricyclic antidepressants, and SRIs. Bupropion, nefazodone, and mirtazapine appear less likely to cause sexual dysfunction. A number of molecularpathways have been implicated in antidepressant-induced sexual adverse events. Serotonin has been hypothesized to inhibit normal sexual response by decreasing dopamine-enhanced libido, arousal and erection and increasing prolactin release from the hypothalamus. SRIs have also been shown to be potent inhibitors of NOS.

Given the high prevalence of antidepressant-induced sexual dysfunction, a prospective, parallel group, randomized, doubleblind, placebo-controlled trial was undertaken to evaluate the safety and efficacy of PDE­5 inhibitors in the treatment of this disorder. Ninety male outpatients at three different university medical centers with major depression in remission and sexual dysfunction associated with either selective or nonselective SRI antidepressant treatment were randomly assigned to take sildenafil at a flexible dose (50–100 mg) for 6 weeks. Multiple different validated and unvalidated questionnaires were administered, including the IIEF. Based on several analyses, the authors concluded that sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with SRI­associated ED. These data provide Level 1 evidence that a PDE­5 inhibitor may be success-fully used to treat Antipsychotic medications are associated with both erectile and ejaculatory dysfunction in up to 50% of patients. Certain antipsychotics, in particular the typical antipsychotics, can exhibit a1 adrenergic antagonism and lead to the unwanted effects of retrograde ejaculation and priapsim. Atypical antipsychotics at high­ doses have been implicated in retrograde ejaculation and priapism as well. Dopamine is considered a key target of neuroleptic medications and is known to have multiple effects in the central nervous system. It is well established that dopamine inhibits prolactin release. Decreases in dopamine action thus lead to hyperprolactinemia. Increased serum levels of prolactin may decrease libido by suppressing gonadotropinreleasing hormone (GnRH) and decreased testosterone levels, resulting in decreased libido, anorgasmia, and ED. In addition, many drugs that produce central nervous system sedation or depression, such as anxiolytics and tranquilizers, are also thought to lead to ED potentially via CNS antidopaminergic effects and increased prolactin release.

CNS sedatives are also known to have residual anticholinergic effects. While acetylcholine plays a significant role in normal erectile function, the use of anticholinergic agents has not been associated with ED as frequently as one might expect. ED has, however, been reported with the anticholinergic antiarrhythmic drug disopyramide. In addition, many of the antidepressants, namely, tricyclics and select SRIs, maintain residual anticholinergic properties. It is possible that the sexual dysfunction from these medications is mediated in part by their anticholinergic properties.