Treatment of Antidepressant-Induced Sexual Dysfunction

Michael J. Gitlin, MD


Medscape Psychiatry & Mental Health eJournal. 1998;3(3) 

In This Article

Treatment of Sexual Side Effects: General Strategies

Effective treatment of antidepressant-induced sexual dysfunction has advanced little since it was first recognized as a significant problem within the last decade.[26] No double-blind treatment study has yet been published, although one with predominantly negative results has been presented.[27] The absence of a systematic study precludes development of a clinically validated treatment algorithm, since comparison of suggested treatments has not been researched. Despite this limitation, treatment of antidepressant-induced sexual dysfunction can be divided into general strategies and antidotes (Table II).[2]

General strategies for treating antidepressant-induced sexual side effects include decreasing the dose, waiting, switching, and transient discontinuation.

Clinical experience suggests that side effects are generally dose-related, making dose reduction a reasonable first strategy to consider.[23,24] The relative paucity of nonsexual side effects seen with SSRIs makes it likely that at least some patients are on higher doses than necessary for antidepressant efficacy. SSRIs typically show a flat dose-response curve in the treatment of depression, meaning that increasing the doses above the typical doses administered is not associated with greater efficacy.[28] The hope is that the dose threshold for efficacy is lower than the dose threshold for sexual side effects, thereby precipitating fewer side effects while preserving efficacy.[28]

The length of time needed for side effects to diminish after dose reduction depends on the half-life of the antidepressant. With fluoxetine's long half-life, a few weeks at the lower dose may be needed to evaluate the regression of side effects. One study demonstrated that 14 days after discontinuing fluoxetine, only 13% of patients with sexual side effects had recovered orgasmic function.[29] For the other serotonergic agents, a period of a few days (for venlafaxine and paroxetine) to a week (for sertraline and fluvoxamine) is probably sufficient to evaluate the success of dose reduction in diminishing sexual side effects.[30]

This strategy of waiting for the patient to adjust to the medication is based on the observation that other drug-induced side effects, such as nausea and excessive stimulation, diminish after several days to weeks of treatment.[31] A few case reports and case series have noted resolution of sexual dysfunction secondary to administration of TCAs or SSRIs.[23,24,32,33] Although accommodation to these side effects may occur, clinical experience demonstrates that the patient usually experiences partial rather than absolute improvement, and it can take many months of treatment, not days to weeks, before improvements are noted.[20] For example, anorgasmia may diminish to delayed orgasm but rarely to full baseline orgasmic function.

Switching to a different antidepressant is a logical and effective strategy when the first prescribed medication produces a higher rate of sexual dysfunction than the alternative. This has been clearly demonstrated in studies in which patients have switched from an SSRI to bupropion or nefazodone.[23,24,29,34]

In the few studies examining this strategy,[31,35] there is no evidence of a depressive relapse when patients are switched across antidepressant classes. However, reemergence of depressive symptoms is always a risk with this strategy. Switching within a medication class is theoretically less risky for inducing relapse, but its efficacy as a strategy for reversing sexual side effects is less clear. Case reports have demonstrated successful switches from one TCA to another.[35,36] Within the SSRI class, no systematic data exist, but anecdotes about successful switches have been reported.[23,24] A study by Ashton and colleagues[13] noted that sexual dysfunction with one SSRI did not necessarily predict dysfunction with another; however, no data were provided.

The most controversial general strategy involves temporary discontinuation of medication. This technique requires either discontinuing the antidepressant for 1 or 2 days or dramatically lowering the dose for several days.[24,37,38] In the largest study examining this strategy, half the patients taking a short half-life SSRI showed clear improvement in sexual functioning after a 2-day discontinuation, whereas patients taking fluoxetine (with its long half-life) showed no improvement.[37] Other cases have been described in which even a 1-day discontinuation of fluoxetine resulted in diminished sexual side effects.[23] One case report described the successful use of a partial drug holiday with fluvoxamine to treat anorgasmia: Fluvoxamine was lowered from 300mg daily to 100mg daily for 2 days, and the patient had complete resolution of anorgasmia.[38] However, then increasing the daily dose to 200mg rather than restoring it to 300mg resulted in the re-emergence of depression.

The strategy of transient medication discontinuation to treat side effects is controversial because of the potential effects on mood, compliance issues, and withdrawal symptoms. In a study by Rothschild,[37] discontinuation of medication was associated with a mild increase in the scores for 2 of 20 patients on the Hamilton Rating Scale for Depression. Some patients may view this strategy as an indication that compliance with antidepressants is not to be attended to seriously. Lastly, transient discontinuation of a short half-life serotonergic medication (especially paroxetine or venlafaxine) confers the risk of inducing an unpleasant withdrawal syndrome characterized by dizziness, light-headedness, insomnia, fatigue, anxiety, nausea, and sensory disturbances.[39,40,41]


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