BACKGROUND: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition.
OBJECTIVES: To assess the effects of SSRIs in the treatment of PE in adult men.
SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status.
SELECTION CRITERIA: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE were administered SSRIs or placebo. We also considered 'no treatment' to be an eligible comparator but did not find any relevant studies.
DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE.
MAIN RESULTS: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better') compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs. SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of 'good' or 'very good'; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs. Secondary outcomes: SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good') compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs. SSRI probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs. SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs. SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence).
AUTHORS' CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.
The benefit is likely to vary by age, as younger men are less likely to have additional erection problems. The authors judged the evidence as moderate: "We judged the quality of evidence to be moderate for SSRIs, helping men’s sense of change with treatment, happiness with intercourse, and feeling of control over ejaculation. The quality of evidence was also moderate for medicine side effects. These results mean that our evaluation is likely to be close to the truth. However, the evidence on improving relationship problems and the time to ejaculation is of low certainty."
It is well documented that medications can be utilized not just for the intended indications, but for their side effects which can be just as helpful. SSRI and SNRIs are known along with TCAs for causing delayed ejaculation and this s/e profile should be utilized more in patients suffering from this condition.