What medications are used to treat premature ejaculation?

Medications for Premature Ejaculation

First-Line Pharmacotherapy Recommendation

Daily SSRI therapy is the most effective first-line pharmacological treatment for premature ejaculation, with paroxetine 10-40 mg daily being the most potent option (8.8-fold increase in ejaculatory latency), though sertraline 50-200 mg daily and fluoxetine 20-40 mg daily are also highly effective and recommended by the American Urological Association. 1, 2

Treatment Algorithm by Clinical Scenario

For Patients with Frequent Sexual Activity (≥2 times per week):

• Start with daily SSRI therapy 2
  • Paroxetine 10-40 mg daily (strongest effect, 8.8-fold IELT increase) 2, 3
  • Sertraline 50-200 mg daily (start at 50 mg, titrate to 200 mg based on response) 1
  • Fluoxetine 20-40 mg daily 2
  • Daily dosing produces substantially greater ejaculatory delay compared to on-demand use 1, 2

For Patients with Infrequent Sexual Activity:

• Dapoxetine 30-60 mg on-demand (1-3 hours before intercourse) 4, 5, 6
  • Specifically approved for PE treatment in many countries (not USA) 4
  • 30 mg dose: 2.5-fold IELT increase; 60 mg dose: 3.0-fold increase 4
  • In men with baseline IELT <30 seconds: 3.4-fold (30 mg) and 4.3-fold (60 mg) increase 4
  • Can be safely combined with PDE5 inhibitors 4

Alternative on-demand options:

• Sertraline 50 mg taken 4-8 hours before intercourse (modestly efficacious but less effective than daily dosing) 1
• Paroxetine 20 mg taken 3-4 hours before intercourse 2
• Tramadol on-demand (up to 2.5-fold IELT increase, but use cautiously due to addiction potential and limited long-term safety data) 4

For Patients Concerned About Systemic Medication Effects:

• Topical lidocaine/prilocaine spray (EMA-approved formulation: lidocaine 150 mg/ml + prilocaine 50 mg/ml) 4, 2
  • Increases IELT up to 6.3-fold over 3 months 4
  • Minimal systemic effects with only minor local side effects (genital hypoesthesia) 4, 2

For Patients with Partial Response to Monotherapy:

• Combination therapy: Daily low-dose SSRI plus on-demand dosing 2
• SSRI plus PDE5 inhibitor: Superior results to SSRI monotherapy, enhances confidence and sexual satisfaction 4

Critical Management Principles

If Erectile Dysfunction Coexists:

Treat ED first or concomitantly, as some acquired PE may be secondary to ED 4, 1

SSRI Dosing Strategy:

• Daily dosing is superior to on-demand dosing for SSRIs 1, 2
• Start sertraline at 50 mg daily and titrate up to 200 mg based on response 1
• Treatment duration is typically long-term, as symptoms often return after discontinuation 7

Important Safety Considerations and Contraindications

Absolute Contraindications:

• Avoid sertraline and all SSRIs in men with bipolar depression (risk of triggering mania) 1, 7

Serious Drug Interactions:

• Screen for concurrent serotonergic medications before prescribing to avoid serotonin syndrome 1, 7
• Sertraline is strongly metabolized by CYP3A4 and CYP2D6, creating numerous pharmacokinetic interaction risks 8

Special Populations Requiring Caution:

• Adolescents and men with comorbid depression, particularly those with suicidal ideation (though no increased suicidal risk found in non-depressed adult men treated for PE) 1

Common Side Effects to Counsel Patients About:

For SSRIs (sertraline): 9

• Ejaculation failure/delayed ejaculation: 14% (vs 1% placebo)
• Decreased libido: 6% (vs 1% placebo)
• Nausea: 25% (vs 11% placebo)
• Diarrhea: 20% (vs 10% placebo)
• Dry mouth: 14% (vs 8% placebo)
• Somnolence: 13% (vs 7% placebo)

For dapoxetine: 4, 10

• Nausea: 11% (30 mg), 22.2% (60 mg)
• Dizziness: 5.9% (30 mg), 10.9% (60 mg)
• Headache: 5.6% (30 mg), 8.8% (60 mg)
• Dose-dependent side effects including diarrhea 4

Critical Clinical Pitfalls to Avoid

Discontinuation Management:

• Never abruptly discontinue daily SSRIs - always taper to prevent SSRI withdrawal syndrome 1, 7

Treatment Adherence:

• Approximately 40% of patients refuse to begin or discontinue SSRI treatment within 12 months due to concerns about taking an antidepressant, effects below expectations, cost, and side effects 1, 7
• Dapoxetine discontinuation rates reach 90% at 2 years, mainly due to cost (29.9%) and disappointment with on-demand nature (25%) 4

Dosing Errors:

• Do not use situational SSRI dosing as first-line when daily dosing is feasible - the efficacy difference is substantial 1

Inappropriate PDE5 Inhibitor Use:

• Do not prescribe PDE5 inhibitors alone to men with PE and normal erectile function 4
• PDE5 inhibitors do not significantly improve IELT but enhance confidence and sexual satisfaction 4

Adjunctive Psychological Therapy

• Consider combining pharmacotherapy with psychotherapy, as psychological factors (anxiety, depression, relationship issues) commonly coexist with PE 2
• Psychological/behavioral therapy may be useful even when no clear psychological etiology is apparent 2
• Patient satisfaction and quality of life should be the primary outcome measures when evaluating treatment success 2