Adding Wellbutrin (Bupropion) to Pristiq for Treatment-Resistant Depression with Sexual Dysfunction
Yes, adding bupropion to desvenlafaxine 50 mg is a clinically appropriate strategy at 6 weeks without adequate response, particularly given the patient's sexual dysfunction and rumination symptoms.
Rationale for Treatment Modification
At 6 weeks, this patient meets criteria for treatment modification. The American College of Physicians strongly recommends that clinicians modify treatment if patients do not have an adequate response to pharmacotherapy within 6 to 8 weeks of initiation 1. The response rate to initial antidepressant therapy may be as low as 50%, and approximately 38% of patients do not achieve treatment response during 6-12 weeks of treatment with second-generation antidepressants 1.
Why Bupropion Addition is Particularly Appropriate Here
Addressing Sexual Dysfunction
Bupropion has a significantly lower rate of sexual adverse events compared to SSRIs and SNRIs 1. This is critical because:
- Desvenlafaxine (Pristiq), as an SNRI, commonly causes sexual dysfunction 1
- Bupropion is associated with significantly lower rates of sexual adverse events than fluoxetine or sertraline 1
- In controlled trials, bupropion effectively reverses antidepressant-associated sexual dysfunction when added to SSRIs or SNRIs 2
- A Cochrane review found that adding bupropion 150 mg twice daily (not once daily) demonstrated benefit over placebo for sexual dysfunction (SMD 1.60,95% CI 1.40 to 1.81) 3
Augmentation Strategy Evidence
Open-label studies support that combination treatment with bupropion and an SSRI or SNRI is effective for treatment-resistant MDD 2. The combination is generally well tolerated, can boost antidepressant response, and can reduce SSRI/SNRI-associated sexual side effects 2.
Practical Implementation
Dosing Strategy
- Start bupropion SR 150 mg once daily for 3-4 days, then increase to 150 mg twice daily 3, 4
- The twice-daily dosing (total 300 mg/day) is more effective for sexual dysfunction than once-daily dosing 3
- Maximum dose can reach 400 mg/day if needed for depression response 5
- Continue the desvenlafaxine 50 mg unchanged initially 2
Consider Dose Optimization of Pristiq First
Before adding bupropion, evaluate whether increasing desvenlafaxine from 50 mg to 100 mg might be appropriate, as 50 mg is the starting dose. However, given the sexual dysfunction already present, adding bupropion rather than increasing the SNRI dose is the more strategic choice 1.
Safety Considerations
Drug Interactions
Bupropion is a CYP2D6 inhibitor, which could theoretically increase desvenlafaxine levels 6. However, this combination is used clinically and is generally well tolerated 2.
Monitoring Requirements
- Assess for seizure risk factors - bupropion may be associated with increased seizure risk, particularly at doses above 450 mg/day 1
- Monitor blood pressure - both desvenlafaxine and bupropion can increase blood pressure 1
- Continue regular monitoring for suicidal ideation, particularly important during treatment changes 1
- Reassess response at 2-4 weeks after bupropion addition 2
Alternative Consideration: Switching vs. Augmentation
While the evidence supports augmentation, one trial found that switching from sertraline to nefazodone reduced sexual dysfunction (RR 0.34,95% CI 0.19 to 0.60) 3. However, nefazodone is no longer clinically available, and there is an absence of randomized trials assessing switching to currently-available antidepressants with lower sexual side effect profiles 3. Given this evidence gap and the patient's partial response (implied by lack of "major" improvement rather than complete non-response), augmentation with bupropion is the more evidence-based approach than switching 2.