In an open study, sildenafil (Viagra) was prescribed for nine women outpatients who reported sexual dysfunction induced by antidepressant medication, primarily selective serotonin reuptake inhibitors. A 50 mg dose of sildenafil was prescribed, and patients were instructed to take it approximately one hour before sexual activity. They were told to increase the dose to 100 mg on the next occasion if they experienced a partial response or a lack of response to sildenafil. The nine patients, all of whom had experienced either anorgasmia or delayed orgasm with or without associated disturbances, reported significant reversal of sexual dysfunction, usually with the first dose of 50 mg of sildenafil.

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Sir: I wish to call your attention to a possible safety issue in the report on the use of sildenafil for antidepressant-related sexual dysfunction. 1 Although the authors screened their patients for medical illness and reported no serious adverse reactions to sildenafil in these antidepressant-treated subjects, the use of this agent in patients taking nefazodone (as in cases 1 and 3) may pose some risk. Nefazodone is a substantial inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system, 2 which also metabolizes sildenafil. 3 In theory, this could lead to abnormally high blood sildenafil levels, which, in turn, may be associated with elevated cardiovascular risk and other adverse events. 3 Thus, clinicians who attempt to treat sexual dysfunction with sildenafil should exercise caution when patients are taking concomitant nefazodone or other CYP3A4 inhibitors.