What is the best Selective Serotonin Reuptake Inhibitor (SSRI) for a patient with premature ejaculation and no significant medical history?

Best SSRI for Premature Ejaculation

Paroxetine is the most effective SSRI for premature ejaculation, providing an 8.8-fold increase in ejaculatory latency time—superior to all other SSRIs—and should be your first-line choice when prescribing daily SSRI therapy. 1, 2

First-Line Pharmacological Approach

Daily SSRI therapy is recommended as the most effective pharmacological treatment for premature ejaculation, with paroxetine demonstrating the strongest ejaculation delay among all SSRIs. 1, 2

Paroxetine: The Most Effective Option

• Start with paroxetine 10-20 mg daily, which can be titrated up to 40 mg based on response 1, 2
• Paroxetine produces an 8.8-fold increase in intravaginal ejaculatory latency time (IELT), significantly outperforming other SSRIs 1, 2
• Daily dosing provides substantially greater ejaculatory delay compared to on-demand administration 1, 3
• On-demand paroxetine 20 mg taken 3-4 hours before intercourse is modestly effective but produces less delay than daily treatment 1, 3

Alternative SSRIs (When Paroxetine is Not Tolerated)

If paroxetine causes intolerable side effects, consider these alternatives in order of efficacy:

• Sertraline 50-200 mg daily: Highly effective second-line option with established guideline support 1, 4
• Fluoxetine 20-40 mg daily: Effective but less potent than paroxetine or sertraline 1
• Citalopram 20-40 mg daily: Effective alternative 1

On-Demand Treatment Options

Dapoxetine (Where Available)

• Dapoxetine 30-60 mg taken 1-3 hours before intercourse is specifically approved for PE in many countries (not FDA-approved in USA) 1, 2
• Produces 2.5-3.0-fold IELT increase with 30 mg and 60 mg doses respectively 1, 2
• In men with baseline IELT <30 seconds, efficacy increases to 3.4-fold (30 mg) and 4.3-fold (60 mg) 1, 2
• Discontinuation rates reach 90% at 2 years, primarily due to cost (29.9%) and disappointment with on-demand nature (25%) 1

Topical Anesthetics

• Lidocaine/prilocaine spray (150 mg/ml + 50 mg/ml) increases IELT up to 6.3-fold over 3 months 1, 2
• Minimal systemic effects with only minor local side effects (genital hypoesthesia) 1
• Consider for patients concerned about systemic medication effects 2

Critical Safety Considerations

Absolute Contraindications

• Never prescribe SSRIs to men with bipolar depression due to risk of triggering mania 1, 4, 5
• Avoid combining with other serotonergic drugs (TCAs, amphetamines, cocaine) due to serotonin syndrome risk 1, 4

Important Warnings

• Never abruptly discontinue daily SSRIs—always taper to prevent SSRI withdrawal syndrome (symptoms include tremor, agitation, diaphoresis, mental status changes) 1, 4
• 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, 4
• Screen for concurrent serotonergic medication use before prescribing 4

Common Side Effects

Paroxetine side effects include 6:

• Ejaculatory disturbance: 13-28% (primarily ejaculatory delay—the desired therapeutic effect)
• Decreased libido: 6-15%
• Nausea: dose-dependent
• Impotence: 2-9%

Sertraline side effects include 7:

• Ejaculatory failure: 17% in males
• Nausea: 26%
• Diarrhea: 18%
• Dry mouth: 16%

Treatment Algorithm

1. If erectile dysfunction coexists, treat ED first or concomitantly, as some acquired PE may be secondary to ED 1, 2, 5

2. For frequent sexual activity (≥2-3 times per week):

   • Start paroxetine 10-20 mg daily 1, 2
   • Titrate to 40 mg if needed after 2-4 weeks 1
   • If intolerable, switch to sertraline 50 mg daily, titrating to 200 mg 1, 4

3. For infrequent sexual activity (<1-2 times per week):

   • Consider dapoxetine 30-60 mg on-demand (where available) 1, 2
   • Alternative: on-demand paroxetine 20 mg 3-4 hours before intercourse 1, 3
   • Alternative: topical lidocaine/prilocaine spray 1, 2

4. For partial responders:

   • Combine daily low-dose SSRI with on-demand dosing 2
   • Consider adding PDE5 inhibitor to SSRI (enhances confidence and sexual satisfaction) 1, 2

Common Pitfalls to Avoid

• Do not use on-demand SSRI dosing as first-line when daily dosing is feasible—the efficacy difference is substantial 4
• Approximately 40% of patients refuse or discontinue SSRI treatment within 12 months due to concerns about taking an antidepressant, effects below expectations, and cost 1, 4
• Address patient concerns about antidepressant use upfront through education 1
• Do not prescribe PDE5 inhibitors alone to men with PE and normal erectile function—they do not significantly improve IELT 1, 5
• Combine pharmacotherapy with psychotherapy when psychological factors are present, as psychological therapy may be useful even without clear psychological etiology 1, 2