Can sertraline (Selective Serotonin Reuptake Inhibitor) be used to treat premature ejaculation?

Sertraline for Premature Ejaculation

Sertraline is an effective, evidence-based first-line treatment for premature ejaculation, recommended by the 2022 AUA/SMSNA guidelines at doses of 50-200 mg daily, with daily dosing superior to on-demand use. 1

Dosing Strategy

Daily dosing is the preferred approach:

• Start with sertraline 50 mg daily and titrate up to 200 mg based on response 1
• Daily administration produces substantially greater ejaculatory delay compared to on-demand dosing 1
• Clinical response typically occurs within the first week of treatment in approximately 69% of responders 2
• Mean ejaculatory latency increases from baseline of 23 seconds to approximately 4.5-16.4 minutes depending on dose 3, 4

On-demand dosing is a less effective alternative:

• Sertraline 50 mg taken 4-8 hours before intercourse (e.g., at 5 PM) is modestly efficacious but produces less ejaculatory delay than daily treatment 1
• On-demand therapy may be combined with an initial trial of daily treatment or concomitant low-dose daily treatment 1
• This approach may be considered for men with infrequent sexual activity 1

Comparative Efficacy

Among SSRIs, paroxetine demonstrates the strongest ejaculation delay (8.8-fold increase in ejaculatory latency time), but sertraline remains highly effective and is recommended as a first-line option 1

Expected Outcomes

• 87.5% clinical response rate in patients completing at least 2 weeks of treatment 2
• Significant improvements in time to ejaculation, number of successful intercourse attempts, and overall sexual satisfaction for both patients and partners 5
• Mean sexual satisfaction scores improve from 0.8/5 pre-treatment to 3.2-3.8/5 with treatment 3

Side Effects and Safety Considerations

Common side effects (from FDA labeling):

• Ejaculatory delay/failure: 14% (vs 1% placebo) - this is the therapeutic effect but can become excessive 6
• Decreased libido: 6% (vs 1% placebo) 6
• Nausea: 25% (vs 11% placebo) 6
• Diarrhea: 20% (vs 10% placebo) 6
• Dry mouth: 14% (vs 8% placebo) 6
• Insomnia: 21% (vs 11% placebo) 6
• Somnolence: 13% (vs 7% placebo) 6

Critical safety warnings:

• Avoid in men with bipolar depression due to risk of triggering mania 1
• Serotonin syndrome risk when combined with other serotonergic drugs (MAOIs, other SSRIs, TCAs, amphetamines, cocaine) - symptoms include clonus, tremor, hyperreflexia, agitation, fever; severe cases may cause seizures and rhabdomyolysis 1
• SSRI withdrawal syndrome can occur with sudden cessation - patients must taper gradually rather than abruptly stopping 1, 7
• Exercise caution in adolescents and men with comorbid depression, particularly those with suicidal ideation, though no increased suicidal risk has been found in non-depressed adult men treated for PE 1

Patient Adherence Challenges

Approximately 40% of patients refuse to begin or discontinue treatment within 12 months due to: 1, 7

• Concerns about taking an antidepressant medication 1, 7
• Treatment effects below expectations 1, 7
• Cost concerns 1, 7
• Side effects 1, 7

Address these barriers proactively through patient education about the off-label use, realistic expectations about efficacy, and discussion of the favorable side effect profile compared to tricyclic antidepressants like clomipramine 1

Duration of Therapy

Long-term treatment is typically required - premature ejaculation usually returns upon discontinuing therapy, so this should be framed as chronic management rather than a cure 1

Clinical Pitfalls to Avoid

• Do not use situational dosing as first-line when daily dosing is feasible - the efficacy difference is substantial 1
• Do not abruptly discontinue daily SSRIs - always taper to prevent withdrawal syndrome 1, 7
• Screen for concurrent use of other serotonergic medications before prescribing to avoid serotonin syndrome 1
• Consider combining with psychotherapy, as psychological factors (depression, anxiety, relationship conflict) commonly coexist with PE 1
• If erectile dysfunction is also present, treat the ED first according to AUA guidelines, as some acquired PE may be secondary to ED 1