What is the appropriate dosage and treatment regimen for a 25-year-old male with premature ejaculation using selective serotonin reuptake inhibitors (SSRIs), specifically dapoxetine (Priligy), at a dose of 30 milligrams (mg) as needed (prn)?

SSRI Treatment for Premature Ejaculation: Dapoxetine 30mg PRN

Dapoxetine 30 mg taken on-demand 1-3 hours before sexual activity is an appropriate and effective first-line treatment for this 25-year-old male with premature ejaculation, though the 60 mg dose provides superior efficacy if the 30 mg dose proves insufficient. 1

Dapoxetine Dosing and Efficacy

Dapoxetine is the only SSRI specifically approved for on-demand treatment of premature ejaculation (though not FDA-approved in the USA, it is approved by the EMA and in many other countries). 1

Starting with 30 mg:

• The 30 mg dose increases intravaginal ejaculatory latency time (IELT) by 2.5-fold on average, from a baseline of approximately 0.9 minutes to 2.78 minutes at 12 weeks 2
• In patients with baseline IELT <30 seconds, the improvement is even greater at 3.4-fold 1
• The medication is effective from the first dose, with no need for a loading period 2
• Take 1-3 hours before anticipated sexual activity for optimal plasma concentrations 1, 2

Dose Escalation Strategy:

• If 30 mg provides insufficient benefit, escalate to 60 mg, which increases IELT by 3.0-fold on average (3.32 minutes at endpoint) and up to 4.3-fold in men with baseline IELT <30 seconds 1, 2
• The 60 mg dose demonstrates superior efficacy but with increased side effects 2, 3

Side Effect Profile

Common adverse events are dose-dependent and generally well-tolerated: 2, 3

• Nausea: 8.7% (30 mg) vs 20.1% (60 mg)
• Diarrhea: 3.9% (30 mg) vs 6.8% (60 mg)
• Headache: 5.9% (30 mg) vs 6.8% (60 mg)
• Dizziness: 3.0% (30 mg) vs 6.2% (60 mg)

These side effects typically do not lead to discontinuation and are acceptable given the non-life-threatening nature of premature ejaculation. 3, 4

Critical Safety Considerations

Contraindications and Warnings:

• Avoid in patients with bipolar depression due to risk of mania 1
• Do not combine with MAOIs due to risk of serotonin syndrome (symptoms include tremor, hyperreflexia, agitation, diaphoresis, fever; severe cases can cause seizures and rhabdomyolysis) 1
• Monitor for suicidal ideation in patients under age 24 or those with comorbid depression, though this risk has not been specifically identified in non-depressed men with PE 1
• Dapoxetine has been associated with vasovagal-mediated syncope, though no other significant cardiovascular adverse events have been identified 4

Alternative SSRI Options if Dapoxetine Unavailable

If dapoxetine is not available (as in the USA), off-label SSRIs are recommended as first-line agents: 1

Daily Dosing Regimens (Generally More Effective):

• Paroxetine 20 mg daily provides the strongest ejaculation delay (8.8-fold increase in IELT), making it the preferred off-label SSRI 1
• Sertraline 50-200 mg daily 1
• Fluoxetine 5-20 mg daily 1
• Clomipramine 25-50 mg daily (higher side effect profile than SSRIs) 1

On-Demand Dosing (Less Effective than Daily):

• Paroxetine 20 mg taken 3-4 hours before intercourse 1
• Sertraline 50 mg taken 4-8 hours before intercourse 1
• Clomipramine 25 mg taken 4-24 hours before intercourse 1

On-demand administration of off-label SSRIs is modestly efficacious but provides substantially less ejaculatory delay than daily treatment in most studies. 1

Treatment Duration and Expectations

• Therapy will likely be needed on a continuing basis, as PE typically returns upon discontinuing treatment 1
• Patient satisfaction and quality of life are the primary outcome targets, not just IELT improvement 1
• Discontinuation rates with dapoxetine reach 90% at 2 years, mainly due to cost (29.9%) and disappointment with on-demand nature (25%) 1

Common Pitfalls to Avoid

• Do not abruptly discontinue daily-dosed SSRIs as this can precipitate SSRI withdrawal syndrome (dizziness, nausea, headache, flu-like symptoms) 1
• Counsel patients that none of the off-label SSRIs are FDA-approved for PE, which may affect patient acceptance 1
• Be aware that 40% of patients refuse or discontinue off-label SSRIs within 12 months due to concerns about taking an antidepressant, suboptimal effects, or cost 1