What are the alternatives to dapoxetine (serotonin-norepinephrine reuptake inhibitor) for treating premature ejaculation?

Alternatives to Dapoxetine for Premature Ejaculation

Yes, there are several effective alternatives to dapoxetine, with topical lidocaine/prilocaine anesthetics and off-label daily SSRIs (particularly paroxetine) being the most evidence-based first-line options.

Primary Alternatives

Topical Anesthetic Agents

• Lidocaine/prilocaine spray or cream is an approved, highly effective alternative that increases intravaginal ejaculatory latency time (IELT) up to 6.3-fold over 3 months, comparable to or exceeding dapoxetine's 2.5-3.0-fold increase 1
• The EMA-approved spray formulation contains lidocaine 150 mg/ml and prilocaine 50 mg/ml, applied 20-30 minutes before intercourse 1
• This option avoids systemic side effects and is particularly suitable for patients concerned about taking oral medications 2
• The main limitation is local penile hypoesthesia and potential partner numbness, which can be minimized by using a condom or washing the penis thoroughly before penetration 1

Off-Label Daily SSRIs

• Paroxetine 10-40 mg daily is the most effective oral alternative, producing an 8.8-fold increase in IELT—substantially greater than dapoxetine 3, 2
• Sertraline 50-200 mg daily and fluoxetine 20-40 mg daily are also effective options recommended by the AUA 3, 2
• Daily SSRI therapy provides more consistent and stronger ejaculatory delay than on-demand dosing (including dapoxetine), though it requires continuous medication use 2
• These medications are used off-label at lower doses than for depression, which reduces the frequency and severity of adverse events 1

On-Demand SSRI Alternatives

• Paroxetine 20 mg taken 3-4 hours before intercourse offers an on-demand alternative similar to dapoxetine's dosing schedule 2
• Clomipramine (a tricyclic antidepressant) 12.5-50 mg on-demand is effective but has a less favorable side effect profile than SSRIs 3

Second-Line Alternatives

Tramadol

• Tramadol on-demand increases IELT up to 2.5-fold and may be considered for patients who have failed first-line therapies 1, 2
• Critical caveat: Use with extreme caution due to opioid-like addiction potential and limited long-term safety data, particularly given the ongoing opioid crisis 1
• Abuse rates are low (0.7%) but prescribing should be judicious 1

Alpha-1 Adrenoreceptor Antagonists

• Alfuzosin and terazosin show modest efficacy in limited studies 1
• Consider only after failure of first-line therapies, as efficacy data remains very limited and additional controlled studies are needed 1

Combination Approaches

Enhanced Efficacy Strategies

• Combining behavioral therapy with any pharmacological approach is more effective than either modality alone (Moderate Recommendation, Grade B evidence) 1
• Daily low-dose SSRI plus on-demand dosing may benefit patients with partial response to monotherapy 2
• If erectile dysfunction coexists, treat ED first or concomitantly, as some acquired PE may be secondary to ED 1, 2
• PDE5 inhibitors (sildenafil, tadalafil) combined with SSRIs show superior results to SSRI monotherapy, enhancing confidence and sexual satisfaction, though PDE5 inhibitors alone do not significantly improve IELT 1, 2

Treatment Selection Algorithm

For patients seeking alternatives to dapoxetine:

1. First choice: Topical lidocaine/prilocaine spray/cream for those wanting to avoid systemic medications or having concerns about daily pill use 1, 2

2. First choice (oral): Daily paroxetine 10-20 mg for patients with frequent sexual activity who prefer the most effective oral option 3, 2

3. Alternative oral: Daily sertraline 50-200 mg or fluoxetine 20-40 mg if paroxetine is not tolerated 3, 2

4. For infrequent sexual activity: On-demand paroxetine 20 mg (3-4 hours before) or clomipramine 2

5. After first-line failure: Consider tramadol on-demand (with caution) or alpha-blockers 1

6. Always add: Behavioral/psychological therapy to any pharmacological approach 1

Important Safety Considerations

SSRI-Specific Warnings

• Avoid sudden cessation or rapid dose reduction of daily SSRIs to prevent withdrawal syndrome 1
• Avoid SSRIs in men with bipolar depression due to risk of mania 1
• Monitor for serotonin syndrome when combining multiple serotonergic agents—symptoms include tremor, hyperreflexia, agitation, diaphoresis, and fever 1
• No increased suicidal ideation has been found in non-depressed men with PE, but caution is warranted in adolescents and those with comorbid depression 1

Common Side Effects

• SSRIs: nausea (11-22%), dizziness (6-11%), headache (6-9%), and sexual side effects including decreased libido 4
• Topical anesthetics: genital hypoesthesia, potential partner numbness 1
• Start SSRIs at the lowest effective dose to minimize adverse events 1

Patient Acceptance Issues

• Approximately 40% of patients refuse or discontinue SSRI treatment within 12 months due to concerns about taking antidepressants, cost, or treatment effects below expectations 1, 3
• Dapoxetine discontinuation reaches 90% at 2 years, mainly due to cost (29.9%) and disappointment with on-demand nature (25%) 1