What are the potential side effects of Selective Serotonin Reuptake Inhibitors (SSRIs) in the treatment of premature ejaculation?

Potential Side Effects of SSRIs in the Treatment of Premature Ejaculation

SSRIs used for premature ejaculation commonly cause side effects including nausea, dry mouth, drowsiness, reduced libido, and delayed ejaculation, with approximately 40% of patients discontinuing treatment within 12 months due to these effects or concerns about taking antidepressants. 1

Common Side Effects

• Sexual side effects: Decreased libido (6% vs 1% with placebo), ejaculatory dysfunction beyond the therapeutic effect (14% vs 1% with placebo), and erectile dysfunction 2
• Gastrointestinal effects: Nausea (25% vs 11% with placebo), diarrhea (20% vs 10% with placebo), dry mouth (14% vs 8% with placebo), dyspepsia (8% vs 4% with placebo), vomiting (4% vs 2% with placebo) 2
• Neurological effects: Somnolence/drowsiness (13% vs 7% with placebo), dizziness (12% vs 7% with placebo), headache (25% vs 23% with placebo), tremor (8% vs 2% with placebo) 2
• Psychiatric effects: Insomnia (21% vs 11% with placebo), nervousness (5% vs 4% with placebo), agitation (5% vs 3% with placebo) 2
• Other common effects: Fatigue (12% vs 7% with placebo), increased sweating (7% vs 2% with placebo) 2

Serious Side Effects and Precautions

• Serotonin Syndrome: A potentially serious complication most often associated with simultaneous use of multiple serotonergic drugs (e.g., SSRI, TCA, recreational drugs like amphetamine or cocaine) 1

  • Symptoms include clonus (cyclic muscle relaxation/contraction), tremor, hyperreflexia, agitation, mental status changes, diaphoresis, and fever
  • Severe cases may lead to seizures and rhabdomyolysis
  • Treatment requires cessation of serotonergic agents; benzodiazepines may help manage symptoms short-term 1

• Risk in Bipolar Disorder: SSRIs should be avoided in men with a history of bipolar depression due to risk of triggering mania 1

• Suicidal Ideation:

  • No significant difference in suicidal ideation has been found in adult men treated with SSRIs for PE 1
  • However, caution is advised when prescribing to adolescents with PE and to men with PE who have comorbid depression, particularly if associated with suicidal ideation 1

• SSRI Withdrawal Syndrome: Patients should avoid sudden cessation or rapid dose reduction of daily dosed SSRIs as this may precipitate withdrawal symptoms 1

Medication Adherence and Discontinuation

• Approximately 40% of patients either refuse to begin or discontinue SSRI treatment (specifically paroxetine) within 12 months 1

• Reasons for discontinuation include:

  • Concerns about taking an antidepressant
  • Treatment effects below expectations
  • Cost concerns
  • Side effects 1, 3

• Dropout rates with fluoxetine treatment for PE:

  • 56% at 6 months
  • 72% at 12 months 3

Dosing Considerations and Side Effect Management

• Side effects appear to be dose-related, with higher doses potentially increasing efficacy but also increasing adverse events 1
• Lower doses used for PE treatment compared to depression may result in fewer and less severe side effects 1
• Situational dosing (taking medication only before sexual activity) may reduce overall exposure to medication and side effects compared to daily dosing 1, 4

Comparative Side Effect Profiles

• SSRIs are generally favored over tricyclic antidepressants like clomipramine due to better side effect profiles 1
• Among SSRIs, paroxetine appears to have the strongest ejaculation-delaying effect but may also have more pronounced side effects 5
• Fluvoxamine appears to have the least ejaculation-delaying effect 5

Patient Counseling Points

• Treatment is likely needed on a continuing basis, as PE usually returns upon discontinuing therapy 1
• Combining behavioral and pharmacological approaches may be more effective than either modality alone 1
• Despite side effects, SSRIs significantly improve self-perceived PE symptoms, satisfaction with intercourse, and control over ejaculation compared to placebo 6

Remember that while SSRIs are effective for PE treatment, they are used off-label for this indication in most countries, and patients should be informed about potential side effects before starting treatment 1.