Before the introduction of fluoxetine, sexual dysfunction in a depressed patient was usually treated as a fundamental aspect of the depression. Most clinicians believed that the sexual dysfunction would respond consistently as symptoms of the mood disorder improved. With the advent of fluoxetine(Drug information on fluoxetine) and other SSRIs, this relatively straightforward relationship became much more complex. To be sure, there had been occasional reports of treatment-induced sexual adverse effects with the monoamine oxidase inhibitors and the tricyclic antidepressants, which usually involved delayed orgasm. However, with the advent of SSRIs, after an initial “don’t ask, don’t tell” period when everyone reported very low rates of sexual adverse effects, the dramatic sexual liability of this class of drugs became well established.13
The good, the bad, and the not-so-bad
First and foremost, it is important to recognize that all SSRIs and serotonin norepinephrine(Drug information on norepinephrine) reuptake inhibitors carry some degree of liability for FSD—regardless of the attempts of pharmaceutical companies to downplay these adverse effects. Although these drugs can cause problems throughout the range of the sexual response cycle, drug-related dysfunctions tend to primarily disrupt orgasm and to result in delayed orgasm and—in some cases—anorgasmia. In contrast, depression-related dysfunctions predominantly involve sexual desire.
SSRI-induced dysfunctions usually emerge during the first or second week following treatment initiation, considerably before the antidepressant effect is manifest. This is one of the reasons it is important to establish a clear sexual functioning baseline for each patient—ideally before the current depressive episode, so that differential effects can be recognized.
Although there is no reliable metric concerning the relative liabilities of different antidepressants to generate sexual adverse effects, a substantial amount of work on the subject has resulted in a rough rank ordering of the differential risk for FSD of the drugs currently on the market (Table 1). The drug consistently judged to have the least potential for FSD is bupropion, followed by nefazodone, mirtazapine(Drug information on mirtazapine), and duloxetine(Drug information on duloxetine).13-15
There is also some evidence that the recently introduced melatonin(Drug information on melatonin) agonist agomelatine may have a favorable profile regarding FSD, but experience with the drug is currently limited.16
The cumulative evidence suggests that the remaining SSRI antidepressants are approximately equivalent in their risk for FSD. The exception is paroxetine(Drug information on paroxetine), which may have a slightly higher liability.13
Treatment of antidepressant-induced FSD
The clinician’s primary responsibility is, of course, to first ensure that the patient’s depression is being effectively treated before turning attention to what some might consider inevitable adverse effects. The difficulty is that for many patients, sexual adverse effects are perceived as an unacceptable burden. These adverse effects are among the leading causes of discontinuation of antidepressant therapy, which can exacerbate the mood disorder.
Fortunately, a number of options are available to treat drug-induced FSD (Table 2). Decreasing the dosage is one option, either through direct reduction or drug holidays. The risk is that the dosage may be too low to be effective, and depression may recur. It is also possible to switch antidepressants with the hope that a new agent may treat the mood disorder without inducing FSD. Another alternative is to try adding a new drug to the treatment regimen as an antidote. The major issue with this approach is simply: will the antidote work?