Side Effects of SSRIs Used in Premature Ejaculation Treatment
SSRIs used for premature ejaculation commonly cause ejaculatory delay (the therapeutic effect), decreased libido, erectile dysfunction, and other sexual side effects, along with potential systemic effects including serotonin syndrome when combined with other serotonergic medications. 1
Common Sexual Side Effects
Daily treatment with SSRIs for premature ejaculation is associated with the following sexual side effects:
- Ejaculatory delay (14% vs 1% with placebo) - this is both the therapeutic effect and a potential side effect when excessive 2
- Decreased libido (6% vs 1% with placebo) 2
- Erectile dysfunction/impotence (frequent adverse event) 2
- Anorgasmia (inability to achieve orgasm) 1
Common Non-Sexual Side Effects
SSRIs commonly cause several non-sexual side effects that patients should be aware of:
Central nervous system effects:
- Somnolence (13% vs 7% with placebo)
- Dizziness (12% vs 7% with placebo)
- Headache (25% vs 23% with placebo)
- Tremor (8% vs 2% with placebo) 2
Gastrointestinal effects:
- Nausea (25% vs 11% with placebo)
- Dry mouth (14% vs 8% with placebo)
- Diarrhea (20% vs 10% with placebo)
- Constipation (6% vs 4% with placebo)
- Dyspepsia (8% vs 4% with placebo)
- Anorexia (6% vs 2% with placebo) 2
Other common effects:
- Fatigue (12% vs 7% with placebo)
- Increased sweating (7% vs 2% with placebo)
- Insomnia (21% vs 11% with placebo) 2
Serious Adverse Effects
Several serious adverse effects require special attention:
Serotonin syndrome: A potentially serious complication most often associated with simultaneous use of multiple serotonergic drugs (SSRIs, TCAs, recreational drugs like amphetamine or cocaine). Symptoms include clonus, tremor, hyperreflexia, agitation, mental status changes, diaphoresis, and fever. Severe cases may involve seizures and rhabdomyolysis. Treatment includes cessation of serotonergic agents and possibly benzodiazepines for symptom management. 1
SSRI withdrawal syndrome: Can occur with sudden cessation or rapid dose reduction of daily SSRIs. Patients should be advised to avoid abrupt discontinuation. 1, 3
Risk in bipolar depression: Treatment with SSRIs should be avoided in men with a history of bipolar depression due to risk of triggering mania. 1
Special Considerations
Suicidality risk: While a systematic review did not identify a significant difference in suicidal ideation in adult men treated with antidepressants versus placebo, caution is suggested when prescribing SSRIs to adolescents with PE and to men with PE and comorbid depressive disorder, particularly when associated with suicidal ideation. 1
Treatment adherence concerns: Approximately 40% of patients either refuse to begin or discontinue SSRI treatment (specifically paroxetine) within 12 months due to concerns about taking an antidepressant, treatment effects below expectations, and cost. 1
Dosing Considerations and Side Effect Management
Different dosing regimens may affect side effect profiles:
Daily dosing: More effective for ejaculatory delay but may have more sustained side effects
- Paroxetine: 10-40 mg/day
- Sertraline: 50-200 mg/day
- Fluoxetine: 20-40 mg/day
- Citalopram: 20-40 mg/day 1
On-demand dosing: May have fewer side effects due to less cumulative exposure but also less ejaculatory delay
- Paroxetine: 20 mg 3-4 hours before intercourse
- Sertraline: 50 mg 4-8 hours before intercourse 1
Comparative Side Effect Profiles
The American Urological Association notes that SSRIs are favored over tricyclic antidepressants like clomipramine because of a better side effect profile, though both are effective for PE treatment. 1
Alternative Treatments with Different Side Effect Profiles
For patients who cannot tolerate SSRI side effects, topical anesthetics (lidocaine/prilocaine) are an alternative first-line treatment. However, these may cause:
- Penile hypoesthesia (numbness)
- Possible absorption by the partner, resulting in discomfort/numbness
- These effects can be mitigated by using a condom or washing the penis prior to penetration 1