How can Wellbutrin (bupropion) be used to manage sexual side effects in patients taking Selective Serotonin Reuptake Inhibitors (SSRIs)?

Managing SSRI-Induced Sexual Dysfunction with Wellbutrin (Bupropion)

Bupropion is highly effective for managing SSRI-induced sexual dysfunction and should be considered as a first-line intervention due to its significantly lower rates of sexual side effects compared to SSRIs. 1

Mechanism and Efficacy

• Bupropion has a favorable sexual side effect profile with significantly lower rates of sexual adverse events compared to fluoxetine or sertraline 2, 1
• When used as an adjunctive treatment for SSRI-induced sexual dysfunction, bupropion has shown global response rates of 46% for women and 75% for men 3
• Bupropion can improve all categories of sexual side effects, with most improvement (>50%) occurring within the first two weeks of treatment and at relatively low doses (100-200 mg/day) 3

Dosing and Administration Options

• Two main approaches for using bupropion to manage SSRI-induced sexual dysfunction:
  • As-needed (PRN) dosing: 75-150 mg taken 1-2 hours before sexual activity 4
  • Scheduled daily dosing: Starting at 100-150 mg/day, with potential increase to 300 mg/day if needed 3, 5
• The PRN approach has been shown to help approximately 38% of patients with SSRI-induced sexual dysfunction 4

Comparative Evidence

• In direct comparisons with sertraline (an SSRI), bupropion SR demonstrated significantly lower rates of sexual dysfunction:
  • Only 15% of men and 7% of women on bupropion experienced sexual dysfunction
  • Compared to 63% of men and 41% of women on sertraline 5
• Sexual dysfunction with SSRIs can occur as early as day 7 of treatment, even at low doses (e.g., sertraline 50 mg/day) 5

Potential Limitations and Contradictory Evidence

• One placebo-controlled study found that a fixed dose of bupropion SR 150 mg/day taken in the morning was not effective for SSRI-induced sexual dysfunction 6
• This contradicts other studies showing efficacy, suggesting that dosing strategy, timing, or individual patient factors may be important 3, 4

Safety Considerations

• Bupropion carries a slightly increased risk of seizures compared to other antidepressants 1
• Common side effects that may limit bupropion use include anxiety and tremor, which led to discontinuation in about 15% of patients in one study 4
• When combining bupropion with SSRIs, monitor for potential drug interactions, particularly with medications metabolized by the cytochrome P450 system 1

Clinical Decision Algorithm

1. Confirm that sexual dysfunction is related to SSRI use (onset coinciding with medication initiation)
2. Rule out other causes of sexual dysfunction (relationship issues, other medications, medical conditions)
3. Consider bupropion as an adjunctive treatment using one of two approaches:
   • For patients who can predict sexual activity: Try PRN dosing with 75-150 mg taken 1-2 hours before sexual activity 4
   • For patients with ongoing sexual activity or unpredictable patterns: Start with scheduled dosing at 100-150 mg/day, increasing to 300 mg/day if needed 3
4. Evaluate response after 2-4 weeks, as most improvement occurs within the first two weeks 3
5. If inadequate response or intolerable side effects occur, consider alternative strategies or referral to sexual health specialist

Monitoring and Follow-up

• Monitor for improvement in specific sexual dysfunction symptoms (desire, arousal, orgasm)
• Watch for potential side effects, particularly anxiety, tremor, and insomnia 4
• Assess for any changes in mood or depression symptoms, as sexual function is an important component of quality of life 5