In an adult patient on a selective serotonin reuptake inhibitor who is experiencing sexual dysfunction (decreased libido, delayed orgasm, anorgasmia), can bupropion be added to alleviate these side effects?

Adding Bupropion for SSRI-Induced Sexual Dysfunction

Adding bupropion to an existing SSRI regimen for sexual dysfunction is not supported by the highest quality evidence; instead, switching from the SSRI to bupropion monotherapy is the recommended strategy. 1

Why Augmentation Is Not Recommended

The most rigorous evidence—a placebo-controlled, double-blind trial—found that adding bupropion SR 150 mg daily to ongoing SSRI therapy produced no significant improvement in sexual dysfunction compared to placebo on any validated measure of sexual function. 2 This directly contradicts the augmentation approach and represents the highest quality study addressing this specific clinical question.

The Evidence-Based Alternative: Switching to Bupropion

The American College of Physicians recommends switching to bupropion as first-line therapy when SSRI-induced sexual dysfunction occurs, based on bupropion's significantly lower sexual dysfunction rates (8-10%) compared to all SSRIs. 1

Supporting Evidence for Switching:

• Direct head-to-head trials demonstrate that bupropion SR causes sexual dysfunction in only 7-15% of patients, compared to 41-63% with sertraline, with differences emerging as early as day 7 of treatment. 3
• When patients switch from SSRIs to bupropion, both depression control and sexual function can be maintained, making this a superior strategy to augmentation. 4

Why the Conflicting Evidence Exists

You'll find older open-label studies suggesting bupropion augmentation works (66% response rate in one 1998 study 5, 46-75% in another 6), but these lack placebo controls. The 2005 placebo-controlled trial 2 supersedes these earlier findings and should guide practice, as it eliminates placebo effect and expectation bias.

Key Limitation of the Negative Trial:

The dose tested was only 150 mg daily. 2 Some open-label data suggest higher doses (up to 300 mg daily) may be more effective 6, but this remains unproven in controlled conditions.

Practical Implementation Algorithm

Step 1: Assess Depression Control

• If depression is well-controlled on current SSRI, proceed with switching strategy
• If depression is poorly controlled, consider that bupropion alone may provide adequate antidepressant effect 1

Step 2: Screen for Bupropion Contraindications

• Do not use bupropion in patients with seizure disorders, eating disorders, or significant agitation 1
• Avoid in patients on tamoxifen for breast cancer (though bupropion has less CYP2D6 inhibition than paroxetine/fluoxetine, some interaction exists) 1

Step 3: Execute the Switch

• Taper the current SSRI appropriately (fluoxetine requires 10-14 days; shorter half-life SSRIs need gradual reduction to prevent withdrawal syndrome) 1, 7
• Initiate bupropion SR 150 mg daily, titrating to 300-400 mg daily as needed for depression control 1
• Never combine with MAOIs due to serotonin syndrome risk 7

Step 4: Monitor Response

• Sexual function typically improves within 1-2 weeks if switching is effective 1
• Reassess depression control at 6-8 weeks; modify if inadequate response 1
• Monitor patients under age 24 for suicidal ideation during any medication changes 7

Alternative If Switching Fails or Is Contraindicated

If bupropion cannot be used or fails to control depression adequately:

• Mirtazapine (15-30 mg daily) has lower sexual dysfunction rates than SSRIs, though it causes sedation and weight gain 1
• Among SSRIs, escitalopram or citalopram have lower sexual dysfunction rates than paroxetine (which has the highest at 70.7%) 1, 7
• Dose reduction of the current SSRI to minimum effective level may help, as sexual side effects are strongly dose-dependent 7, 8

Critical Safety Considerations

• Monitor for serotonin syndrome if any serotonergic agents are combined (tremor, hyperreflexia, agitation, diaphoresis, fever) 7, 8
• Always taper SSRIs gradually to prevent withdrawal syndrome (dizziness, nausea, headache, flu-like symptoms) 7, 8
• Ensure baseline testosterone levels are normal (>300 ng/dL), as low testosterone contributes to decreased libido independent of SSRI effects 1

Common Pitfall to Avoid

Do not add bupropion 150 mg daily and expect meaningful improvement based on the placebo-controlled evidence. 2 If you choose to attempt augmentation despite the negative trial data (perhaps at higher doses), set appropriate expectations with the patient and have a clear plan to switch to monotherapy if augmentation fails within 6-8 weeks. 1