Managing SSRI-related sexual side effects in primary care

Sexual problems affect at least 50% of patients taking SSRIs and SNRIs—both women and men. This wouldn’t be obvious gleaning the FDA package inserts, where the issue is notoriously underreported. The package insert for Paxil® (paroxetine), for instance, reports rates of decreased libido and anorgasmia of only 0-9% and 2-9%, respectively, in women, and low rates in men.

All phases of the sexual cycle can be affected by chronic SSRI treatment. Inability to achieve orgasm is especially common, best illustrated by off-label use of SSRIs for premature ejaculation. Unfortunately, sexual side effects typically persist—only 5-10% of SSRI-treated patients report spontaneous remission of these effects after 6 months of treatment.

So how can we manage a patient finding clinical benefit with their SSRI but are bothered by treatment-emergent sexual issues?

The first principle is to ensure that the daily dose is optimal—one that strikes the best possible balance between benefits and side effects. SSRIs are commonly titrated too quickly without taking time to appreciate the effects of a particular dose, which accumulate over 4-6 weeks. Providers should ask the patient to recall (to the best of their ability) how their medication was titrated. If dose adjustments were too fast, too high, or environmental stressors have lessened, this may justify a small dose reduction. Given that sexual side effects with SSRIs are dose-dependent, dose reductions may attenuate these unwanted effects while possibly maintaining therapeutic efficacy.

Although all SSRIs and SNRIs are highly likely to cause sexual dysfunction (paroxetine may carry the highest risk via inhibition of nitric oxide synthesis), some are more conducive than others for achieving that dosage balance. For example, the small and unscored escitalopram tablets make it hard to explore dosages other than 10mg, 15mg and 20mg. On the other hand, sertraline’s therapeutic dosage ranges from 50mg to 200mg daily, with adjustments that can be made in 12.5mg increments. SSRIs like sertraline can make it easier to work out that ideal balance for your patient.

Drug holidays, although intuitive, are not recommended because of the substantial risk of interpose withdrawal symptoms that can be very uncomfortable and destabilize the patient’s underlying mental health condition.

If the drug dosage has been optimized, but sexual problems continue to be problematic, we have a few pharmacologic options at our disposal. Adjunctive bupropion (150mg-300mg XL daily recommended) or buspirone (titrated to high doses—20-30mg BID) are worth trying and may provide some relief, although data are mixed. They are also generally well-tolerated and easy to discontinue.

In men, the PDE5 inhibitors are an excellent choice. Sildenafil 25-50mg PRN an hour before sexual activity, or once-daily tadalafil (2.5-5mg) can improve erection quality which can indirectly improve anorgasmia.

Filbanserin (Addyi®), a drug approved for low libido in women, has inconsistent efficacy in general and unfortunately cannot be recommended for SSRI-associated sexual dysfunction in women, particularly when anorgasmia is the principle issue.

In very select patients without a history of substance abuse, PRN cannabis can improve subjective pleasure and orgasm associated with sexual intercourse, but comes at a risk of abuse, dependence, destabilizing a patient’s mood disorder, and “surfacing” a bipolar diathesis.