What is the first‑line treatment for premature ejaculation in an adult male?

First-Line Treatment for Premature Ejaculation

Daily SSRI therapy is the first-line pharmacological treatment for premature ejaculation, with paroxetine 10-20 mg daily being the most effective option, increasing ejaculatory latency 8.8-fold over baseline. 1

Treatment Algorithm

Step 1: Rule Out Erectile Dysfunction First

• If erectile dysfunction coexists with PE, treat the ED first or concomitantly, as many men develop secondary PE due to anxiety or the need for intense stimulation to maintain erection. 1
• Some acquired PE may resolve completely when the underlying ED is effectively treated. 1

Step 2: Select First-Line Pharmacological Therapy Based on Sexual Activity Frequency

For regular sexual activity (frequent intercourse):

• Daily SSRI therapy provides the most consistent and strongest ejaculatory delay compared to on-demand dosing. 1
• Paroxetine 10-20 mg daily is the most effective SSRI, producing an 8.8-fold increase in ejaculatory latency. 1
• Alternative daily SSRIs include sertraline 25-200 mg daily or fluoxetine 5-20 mg daily. 1
• Daily dosing requires 1-2 weeks to achieve full therapeutic effect. 2

For infrequent sexual activity:

• Dapoxetine 30-60 mg taken 1-3 hours before intercourse is specifically approved for PE in many countries (not FDA-approved in USA). 1
• Dapoxetine 60 mg produces a 3.0-fold increase in IELT overall, and a 4.3-fold increase in men with baseline IELT <30 seconds. 1
• On-demand paroxetine 20 mg taken 3-4 hours before intercourse is also effective but provides less delay than daily treatment. 1

For patients concerned about systemic medication effects:

• Topical lidocaine 2.5%/prilocaine 2.5% cream (EMLA) applied 20-30 minutes before intercourse is a suitable first-line alternative. 1
• The EMA-approved spray formulation (lidocaine 150 mg/ml + prilocaine 50 mg/ml) increases IELT up to 6.3-fold over 3 months with minimal systemic effects. 1

Important Clinical Considerations and Pitfalls

SSRI Side Effects and Discontinuation

• Approximately 40% of patients discontinue SSRI treatment within 12 months due to side effects or concerns about taking antidepressants. 3
• Common side effects include nausea, dry mouth, drowsiness, reduced libido, and delayed ejaculation (potentially progressing to ejaculation failure). 3
• Side effects are dose-related, so starting with lower doses may improve tolerability. 3
• Patients must taper daily SSRIs rather than stopping abruptly to avoid SSRI withdrawal syndrome. 3

Serotonin Syndrome Warning

• Avoid combining SSRIs with other serotonergic drugs due to risk of serotonin syndrome, which presents with clonus, tremor, hyperreflexia, agitation, mental status changes, diaphoresis, and fever. 3
• Severe cases may lead to seizures and rhabdomyolysis. 3
• SSRIs should be avoided in men with bipolar depression due to risk of triggering mania. 3

Topical Anesthetic Pitfalls

• Avoid prolonged application (30-45 minutes) of lidocaine/prilocaine cream, as excessive penile numbness can cause loss of erection. 1
• The penis must be washed thoroughly before intercourse to prevent partner vaginal numbness, which is a frequent complaint limiting acceptability. 1
• A condom may be used during the application period, then removed and the penis washed before intercourse. 1

Combination Therapy for Partial Responders

• Combination of daily low-dose SSRI plus on-demand dosing may be considered for patients with partial response to monotherapy. 1
• For men with comorbid PE and ED, combining an SSRI with a PDE5 inhibitor shows superior results to SSRI monotherapy and enhances confidence and sexual satisfaction. 1
• Co-administration of sildenafil with on-demand paroxetine enhances ejaculatory delay but increases headache and flushing. 1
• PDE5 inhibitors should not be prescribed alone to men with PE and normal erectile function, as they do not significantly improve IELT. 1

Behavioral Therapy Integration

• Combining behavioral techniques with pharmacologic treatment yields superior outcomes compared to either approach alone (Grade B evidence). 1
• Psychological/behavioral therapy may be useful even when no clear psychological etiology is apparent. 1
• Behavioral strategies carry no fertility risks and should be emphasized when couples are trying to conceive. 1

Treatment Goals

• Patient and partner satisfaction is the primary therapeutic target, not just ejaculatory latency improvement. 1
• Treatment is likely needed on a continuing basis, as PE usually returns upon discontinuing therapy. 3
• Clinicians should regularly reassess alternative therapeutic options and modify the regimen as needed to optimize outcomes. 1

Off-Label Use Disclosure

• None of the SSRIs are FDA-approved specifically for PE in the USA, so doses and dosing regimens deviate from FDA-approved indications. 1
• Patients should be informed about potential side effects before starting treatment. 3