What is the best Selective Serotonin Reuptake Inhibitor (SSRI) for treating premature ejaculation?

Paroxetine Is the Most Effective SSRI for Premature Ejaculation

Paroxetine 10-20 mg daily is the most effective SSRI for treating premature ejaculation, increasing ejaculatory latency 8.8-fold over baseline. 1

Comparative Effectiveness of SSRIs

• Paroxetine demonstrates superior efficacy compared to other SSRIs, with daily dosing of 10-20 mg providing the most consistent improvement in ejaculatory control 1
• Other effective SSRIs include:
  • Sertraline (25-200 mg daily)
  • Fluoxetine (5-20 mg daily)
  • Clomipramine (a tricyclic antidepressant with SRI effects) at 25-50 mg daily 2, 1

Dosing Strategies

• Daily dosing regimen:

  • Provides more consistent and stronger ejaculatory delay than on-demand dosing 1
  • Paroxetine: 10-20 mg daily (most effective dose) 1
  • Sertraline: 25-200 mg daily 2
  • Fluoxetine: 5-20 mg daily 2

• On-demand (situational) dosing:

  • Less effective than daily dosing but still beneficial 1
  • Paroxetine: 20 mg taken 3-4 hours before intercourse 1, 3
  • Sertraline: 50 mg taken 4-8 hours before intercourse 2
  • Clomipramine: 25 mg taken 4-24 hours before intercourse 2

Side Effect Considerations

• Common side effects include nausea, dry mouth, drowsiness, reduced libido, and delayed ejaculation 4
• Approximately 40% of patients discontinue treatment within 12 months due to side effects or concerns about taking antidepressants 4, 5
• Side effects appear to be dose-related, with higher doses potentially increasing both efficacy and adverse events 4
• Lower doses used for PE treatment compared to depression may result in fewer and less severe side effects 4
• SSRIs are generally favored over tricyclic antidepressants like clomipramine due to better side effect profiles 4

Treatment Selection Algorithm

1. First choice: Daily paroxetine 10-20 mg (most effective option) 1
2. Alternative options:
   • For patients concerned about daily medication: On-demand paroxetine 20 mg taken 3-4 hours before intercourse 1, 3
   • For patients with partial response: Consider combination therapy with daily low-dose SSRI and on-demand dosing 1
   • For patients with side effects to paroxetine: Try sertraline 25-200 mg daily or fluoxetine 5-20 mg daily 2, 6

Important Clinical Considerations

• Treatment is likely needed on a continuing basis, as PE usually returns upon discontinuing therapy 2, 4
• Patients should be informed about potential side effects before starting treatment 4
• Avoid sudden discontinuation of daily SSRIs to prevent withdrawal symptoms 4
• SSRIs should be avoided in men with a history of bipolar depression due to risk of triggering mania 4
• Be cautious about potential drug interactions, particularly with monoamine oxidase inhibitors, which can cause serotonin syndrome 2, 4

Comparative Studies

• A direct comparison between sertraline and fluoxetine showed similar efficacy (38.7% cure rate with sertraline vs. 30.8% with fluoxetine) and side effect profiles (25.8% with sertraline vs. 23% with fluoxetine) 6
• A study comparing daily vs. on-demand paroxetine found that daily dosing followed by on-demand dosing maintained improved ejaculatory control in 36 out of 53 men, while initial on-demand dosing was less effective 7