Clinical Question

Are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) safe and effective for the treatment of premature ejaculation in adult men?

Evidence-Based Answer

SSRIs and SNRIs increase the ejaculatory latency time (mean difference [MD] = 3.09 minutes; 95% CI, 1.94 to 4.25 minutes) and improve the satisfaction of the experience (relative risk [RR] = 1.63; 95% CI, 1.42 to 1.87) compared with placebo. However, adverse effects cause a substantial number of men to stop treatment (RR = 3.80; 95% CI, 2.61 to 5.51).¹ (Strength of Recommendation: B, inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

According to the International Society for Sexual Medicine, premature ejaculation is a sexual dysfunction characterized by penile ejaculation that always or nearly always occurs before or within one minute of sexual penetration.² It is either present from the patient's first sexual encounter (lifelong premature ejaculation) or a bothersome decrease in ejaculatory latency (secondary or acquired), often to three minutes or less. Causes of acquired premature ejaculation include sexual performance anxiety, psychological and relationship problems, erectile dysfunction, and use of or withdrawal from medications or recreational drugs. Rarely, hyperthyroidism or prostatitis can contribute to premature ejaculation. In lifelong and acquired premature ejaculation, there is an inability to delay ejaculation during all or nearly all instances of sexual penetration, leading to personal distress or avoidance of sexual intimacy.^1,3,4 

Premature ejaculation is estimated to occur in 4% to 39% of men in the general population.⁵ Premature ejaculation can be treated using a multimodal approach, including behavioral therapy, topical agents, and oral medications.⁵ The authors of this Cochrane review sought to determine whether SSRIs or SNRIs can improve symptoms of premature ejaculation in adult men. 

This Cochrane review included 31 randomized controlled trials in which 8,254 participants received SSRIs (n = 4,990), another drug, or placebo.¹ The studies included only men 18 years and older with lifelong premature ejaculation; 4,193 men received dapoxetine, an SSRI that is marketed to promote ejaculatory delay and is not available in the United States. The studies were conducted across 14 countries, including three in the United States and Canada. A range of other SSRIs and SNRIs were used at different dosages in the studies, including fluoxetine (Prozac), duloxetine (Cymbalta), citalopram (Celexa), sertraline (Zoloft), paroxetine (Paxil), escitalopram (Lexapro), and fluvoxamine. In some studies, the SSRI was prescribed as a daily medication for premature ejaculation. In other studies, the medication was meant to be used on demand just before sexual activity. Dapoxetine, paroxetine, and citalopram were in the on-demand arms. 

Perception of change with treatment was evaluated using the Clinical Global Impression of Change questionnaire, a validated clinician-completed instrument to assess response to treatment. Participants who received an SSRI or SNRI were two times more likely to report change with treatment compared with those who received placebo (number needed to treat [NNT] = 5; 95% CI, 4 to 7). Participants who received an SSRI or SNRI had increased intravaginal ejaculatory latency time compared with those who received placebo (MD = 3.09 minutes; 95% CI, 1.94 to 4.25 minutes). Satisfaction with intercourse and perceived control over ejaculation with dapoxetine were measured using a validated instrument called the Premature Ejaculation Profile questionnaire. Participants treated with an SSRI or SNRI were more likely to experience satisfaction (RR = 1.63; 95% CI, 1.42 to 1.87) and to perceive control over ejaculation (RR = 2.29; 95% CI, 1.72 to 3.05) compared with those who were given placebo. 

When dapoxetine was used daily or on demand just before sexual activity, the effectiveness of 30-mg and 60-mg dosing for premature ejaculation was similar for all of the above outcomes. However, participants who received 60 mg of dapoxetine daily or on demand were much more likely to withdraw from the studies because of adverse effects compared with those who received 30 mg of dapoxetine. A substantial number of participants withdrew from the studies because of adverse effects with SSRI use (number needed to harm [NNH] = 33; 95% CI, 20 to 59). The adverse effects experienced by these participants were not described in this review. 

Similar to the findings in an older meta-analysis,⁶ this Cochrane review revealed that paroxetine was the most effective long-acting SSRI (MD for increased latency time = 6.51 minutes; 95% CI, 0.33 to 12.68 minutes). Citalopram was also highly effective (MD for increased latency time = 4.85 minutes; 95% CI, 3.14 to 6.56 minutes). 

It is important to identify and address acquired causes of premature ejaculation at presentation. The International Society for Sexual Medicine supports considering off-label daily dosing of SSRIs such as paroxetine, sertraline, citalopram, and fluoxetine, as well as the tricyclic antidepressant clomipramine (Anafranil) or the off-label, on-demand dosing of dapoxetine for the treatment of lifelong and acquired premature ejaculation.² Physicians should monitor patients closely for adverse effects during treatment. 

The practice recommendations in this activity are available at https://www.cochrane.org/CD012799.

Editor's Note: The NNT and NNH and their corresponding CIs reported in this Cochrane for Clinicians were calculated by the authors based on raw data provided in the original Cochrane review.