What is the best medication for premature ejaculation?

Best Medication for Premature Ejaculation

Daily paroxetine 10-40 mg is the single most effective pharmacological treatment for premature ejaculation, producing an 8.8-fold increase in ejaculatory latency—the strongest effect of any medication. 1

First-Line Treatment Recommendation

Start with daily paroxetine 10-20 mg as your first-choice medication. 1 The American Urological Association explicitly recommends daily SSRI therapy as the most effective pharmacological approach, with paroxetine demonstrating superior efficacy compared to all other SSRIs. 1

Alternative Daily SSRIs (if paroxetine is not tolerated or contraindicated):

• Sertraline 50-200 mg daily (start at 50 mg, titrate based on response) 2
• Fluoxetine 5-20 mg daily 1

All daily SSRIs provide substantially greater ejaculatory delay than on-demand dosing. 1, 2

On-Demand Treatment Options

If daily medication is unacceptable due to infrequent sexual activity or patient preference for situational dosing:

First Choice for On-Demand:

Dapoxetine 30-60 mg taken 1-3 hours before intercourse is specifically approved for PE in many countries (though not FDA-approved in the US). 1 It produces a 2.5-3.0-fold increase in IELT with the 30 mg dose and 3.0-fold with 60 mg. 1, 3, 4 In men with baseline IELT <30 seconds, dapoxetine 60 mg produces a 4.3-fold increase. 1

Critical limitation: Dapoxetine has 90% discontinuation rates at 2 years, mainly due to cost and disappointment with the on-demand nature. 1

Alternative On-Demand Options:

• Paroxetine 20 mg taken 3-4 hours before intercourse (less effective than daily dosing but still efficacious) 1
• Sertraline 50 mg taken 4-8 hours before intercourse (modestly efficacious but produces less delay than daily treatment) 2
• Topical lidocaine/prilocaine spray (EMA-approved formulation: lidocaine 150 mg/ml + prilocaine 50 mg/ml) increases IELT up to 6.3-fold over 3 months with minimal systemic effects 1, 5

Treatment Algorithm

1. Assess sexual activity frequency:

   • Frequent sexual activity → Daily SSRI (paroxetine preferred)
   • Infrequent sexual activity → On-demand dapoxetine or topical anesthetic 1

2. Screen for contraindications:

   • Avoid SSRIs in bipolar depression (risk of triggering mania) 2, 6
   • Screen for concurrent serotonergic medications (serotonin syndrome risk) 2
   • Exercise caution in adolescents and men with comorbid depression/suicidal ideation 2

3. If erectile dysfunction coexists, treat ED first or concomitantly, as some acquired PE may be secondary to ED. 1 PDE5 inhibitors should not be prescribed alone for PE with normal erectile function. 1

4. For partial response to monotherapy:

   • Combine daily low-dose SSRI with on-demand dosing 1
   • Combine SSRI with PDE5 inhibitor (shows superior results to SSRI monotherapy) 1

Critical Safety Considerations

Common Side Effects (from FDA labels):

• Paroxetine: Ejaculatory disturbance (13-28%), decreased libido (6-15%), impotence (2-9%), nausea, dizziness 7
• Sertraline: Ejaculatory failure (17-21%), nausea (26-30%), diarrhea (18-24%), insomnia (16-28%) 8

Important Warnings:

• Never abruptly discontinue daily SSRIs—always taper to prevent SSRI withdrawal syndrome 2
• Approximately 40% of patients refuse or discontinue SSRI treatment within 12 months due to concerns about taking antidepressants, side effects, or cost 2, 6
• Serotonin syndrome risk when combining with other serotonergic medications 2

Topical Therapy for Patients Concerned About Systemic Effects

Topical lidocaine/prilocaine cream or spray provides moderate effectiveness with minimal systemic absorption. 1 This is the preferred option for patients who want to avoid systemic medication effects or have contraindications to SSRIs. 1

Adjunctive Psychological Therapy

Combine pharmacotherapy with psychological/behavioral therapy, as psychological factors (anxiety, depression, relationship issues) commonly coexist with PE and should be addressed. 1 Psychological therapy may be useful even when no clear psychological etiology is apparent. 1