What is the difference between Wellbutrin (bupropion) XL and SR in managing sexual dysfunction caused by Selective Serotonin Reuptake Inhibitors (SSRIs)?

Wellbutrin XL vs SR for SSRI-Induced Sexual Dysfunction

Both Wellbutrin XL and SR formulations are effective for managing SSRI-induced sexual dysfunction, but there is no evidence demonstrating superiority of one formulation over the other—the key is achieving adequate total daily dosing of 150-400 mg/day, with SR formulations typically dosed twice daily and XL once daily. 1

Primary Recommendation

Switch from the SSRI to bupropion (Wellbutrin) as first-line therapy when sexual dysfunction occurs, as bupropion has dramatically lower rates of sexual dysfunction (8-10%) compared to SSRIs like sertraline (14-63%) or paroxetine (70.7%). 1, 2

Formulation Considerations

Dosing Differences

• Bupropion SR requires twice-daily dosing (typically 150 mg BID), while XL allows once-daily dosing (150-450 mg daily), which may improve adherence but does not change efficacy for sexual dysfunction 1
• One study found that bupropion SR 150 mg once daily was NOT effective as an adjunct to SSRIs for treating sexual dysfunction, suggesting that adequate dosing (at least 150 mg twice daily or equivalent) is critical 3
• The effective dose range for managing sexual dysfunction is 150-400 mg/day total, regardless of formulation 1

Evidence for Bupropion vs SSRIs

• In head-to-head trials, bupropion SR caused orgasmic dysfunction in only 15% of men and 7% of women, compared to 63% of men and 41% of women on sertraline 4
• Sexual dysfunction with sertraline appeared as early as day 7 at doses of just 50 mg/day and persisted throughout 16 weeks of treatment 4
• When used as an adjunct (added to ongoing SSRI), bupropion successfully reversed sexual dysfunction in 66% of patients, with 69% of specific sexual complaints improving 5

Treatment Algorithm

Step 1: Assess Severity and Type

• Determine whether the patient has erectile dysfunction, orgasmic dysfunction, decreased libido, or ejaculatory problems, as this guides additional interventions 1

Step 2: Switch to Bupropion

• Discontinue the SSRI (taper fluoxetine over 10-14 days to avoid withdrawal) and initiate bupropion SR 150 mg BID or XL 150-300 mg daily 1, 2
• Monitor for therapeutic response within 1-2 weeks and adjust dose up to 400 mg/day if needed by 6-8 weeks 2

Step 3: Consider Adjunctive Strategies if Switching is Not Possible

• For men with erectile dysfunction who must remain on an SSRI, add a PDE5 inhibitor (sildenafil or tadalafil), which has robust evidence for improving erectile function 1
• Bupropion can be added as an adjunct to the SSRI at 75-150 mg 1-2 hours before sexual activity (p.r.n. dosing) or as scheduled dosing up to 75 mg TID 5

Critical Safety Warnings

Seizure Risk

• Bupropion increases seizure risk, particularly at doses above 300 mg/day or in patients with predisposing factors (history of seizures, eating disorders, abrupt alcohol/benzodiazepine discontinuation) 1, 2
• Bupropion is absolutely contraindicated in patients with seizure disorders or bulimia/anorexia nervosa 2

When NOT to Use Bupropion

• Do not use bupropion in agitated patients, as it can worsen agitation and insomnia 2
• For patients with comorbid anxiety disorders, SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety 1

Important Clinical Caveats

• Sexual dysfunction rates are vastly underreported in clinical trials—real-world incidence is likely substantially higher than published figures 1, 2
• Among SSRIs, paroxetine has the absolute highest rates of sexual dysfunction (70.7%) and should be avoided entirely when sexual function is a concern 2
• If an SSRI must be continued, sertraline or citalopram are preferred over paroxetine or fluoxetine 2
• Nausea and gastrointestinal disturbances are more common with sertraline, while insomnia and dry mouth are more common with bupropion 6, 7

Monitoring Requirements

• Assess for improvement in sexual function and depressive symptoms within 1-2 weeks of initiating bupropion 2
• If inadequate response occurs by 6-8 weeks, increase the dose or consider adding a PDE5 inhibitor for erectile dysfunction 1, 2
• Discontinuation of bupropion due to side effects (primarily anxiety and tremor) occurs in approximately 15% of patients 5