What are the first-line treatment options for a patient with premature ejaculation?

First-Line Medications for Premature Ejaculation

Daily SSRI therapy is the most effective first-line pharmacological treatment for premature ejaculation, with paroxetine 10-20 mg daily being the preferred agent, providing an 8.8-fold increase in ejaculatory latency time over baseline. 1, 2

Treatment Algorithm

Step 1: Rule Out Erectile Dysfunction First

• If ED coexists with PE, treat the erectile dysfunction first or concomitantly, as many men with ED develop secondary PE due to anxiety or the need for intense stimulation to maintain erection 1, 2
• Some acquired PE may resolve when the underlying ED is effectively treated 3

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

For Regular Sexual Activity (Daily SSRI Preferred):

Primary Option - Paroxetine:

• Start paroxetine 10-20 mg daily, which provides the strongest ejaculatory delay (8.8-fold increase in IELT) 1, 2, 4
• Daily dosing provides more consistent and stronger ejaculatory delay than on-demand dosing 1, 4
• Common side effects include ejaculatory disturbance (13%), decreased libido (3%), somnolence (23%), and nausea (26%) 5

Alternative Daily SSRIs:

• Sertraline 25-200 mg daily (for diabetic patients, start at 50 mg and titrate to 200 mg based on response) 1, 2, 4
• Fluoxetine 5-20 mg daily 1
• These provide consistent ejaculatory delay, though less potent than paroxetine 1, 2

For Infrequent Sexual Activity (On-Demand Dosing):

Dapoxetine (where available, not FDA-approved in USA):

• Dapoxetine 30-60 mg taken 1-3 hours before intercourse 1, 4
• Produces 2.5-3.0-fold increase in IELT with 30 mg dose, and 3.0-fold with 60 mg dose 1
• In men with baseline IELT <30 seconds, provides 3.4-fold (30 mg) and 4.3-fold (60 mg) increase 1
• Discontinuation rates reach 90% at 2 years, mainly due to cost and disappointment with on-demand nature 1

On-Demand SSRIs (less effective than daily dosing):

• Paroxetine 20 mg taken 3-4 hours before intercourse provides less ejaculatory delay than daily treatment 1
• On-demand clomipramine is also an option 2

Step 3: Topical Anesthetics as Alternative First-Line

For patients concerned about systemic SSRI effects:

• Topical lidocaine/prilocaine spray (EMA-approved formulation: lidocaine 150 mg/ml + prilocaine 50 mg/ml) 1
• Increases IELT up to 6.3-fold over 3 months with minimal systemic effects 1, 4
• Only minor local side effects (genital hypoesthesia) 1
• Lidocaine/prilocaine cream provides moderate effectiveness with minimal systemic effects 1

Critical Safety Considerations

SSRI Discontinuation:

• Never abruptly discontinue daily SSRIs—always taper to prevent SSRI withdrawal syndrome 2, 4
• Screen for concurrent serotonergic medications before prescribing to avoid serotonin syndrome 2

Monitoring Requirements:

• Monitor patients under age 24 or those with comorbid depression for suicidal ideation 4
• Caution when prescribing SSRIs to adolescents with PE, though elevated risk of suicidal ideation has not been found in trials with non-depressed men with PE 2

Combination Therapy for Partial Responders

If monotherapy provides inadequate response:

• Combine daily low-dose SSRI plus on-demand dosing 1, 4
• For patients with comorbid PE and ED: combine SSRI plus PDE5 inhibitor, which shows superior results to SSRI monotherapy and enhances confidence and sexual satisfaction 1
• Do not prescribe PDE5 inhibitors alone to men with PE and normal erectile function, as they do not significantly improve IELT 1

Treatment Outcome Priorities

Patient and partner satisfaction is the primary target outcome for PE treatment, not just ejaculatory latency improvement. 3, 2, 4 Discuss risks and benefits of all treatment options before initiating therapy, emphasizing that PE is not life-threatening and safety should be a primary consideration 2

Common Pitfalls to Avoid

• Do not use escitalopram in patients with bipolar depression due to risk of mania 4
• Never combine escitalopram with MAOIs due to risk of serotonin syndrome 4
• Avoid surgical interventions and neuromodulation, as current guidelines do not recommend these treatments due to safety concerns 6
• Remember that none of these medications are FDA-approved specifically for PE in the USA, so doses and dosing regimens deviate from FDA-approved indications 3