Adding Wellbutrin (Bupropion) to Prestiq (Desvenlafaxine)
Yes, adding Wellbutrin (bupropion) to Prestiq (desvenlafaxine) is a reasonable and evidence-supported augmentation strategy for patients with inadequate response to desvenlafaxine monotherapy. 1
Evidence for Augmentation Strategy
Guideline Support for Bupropion Augmentation
The American College of Physicians guidelines from 2016 specifically address augmentation strategies when patients fail initial treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) like desvenlafaxine. 1
Low-quality evidence demonstrates that augmenting SNRI treatment (specifically citalopram, which shares similar mechanisms with desvenlafaxine) with bupropion shows no difference in response or remission rates compared to buspirone, but bupropion decreases depression severity more effectively than buspirone. 1
Moderate-quality evidence indicates that discontinuation due to adverse events was lower with bupropion augmentation compared to buspirone augmentation. 1
Low-quality evidence showed no difference in suicidal ideas and behavior or serious adverse events when augmenting with bupropion. 1
Clinical Trial Evidence
A prospective open-label trial demonstrated that 54% of patients who had inadequate response to SSRIs or venlafaxine (an SNRI similar to desvenlafaxine) achieved response when bupropion SR was added at doses of 150-300 mg daily. 2
A case report documented successful combination therapy with venlafaxine (the parent compound of desvenlafaxine) and bupropion in treatment-resistant depression, with significant reduction in depressive symptoms and increased social function. 3
A randomized controlled trial showed that bupropion augmentation of SSRIs resulted in 60% remission rates compared to 24% with placebo augmentation in patients with partial response. 4
Practical Implementation
Dosing Strategy
Start bupropion at 100-150 mg daily and increase to 150-450 mg daily as tolerated. 1
The typical effective augmentation dose range is 150-300 mg per day of bupropion SR. 2
Continue the current desvenlafaxine 50 mg daily dose unchanged. 5
Timeline for Assessment
Assess response within 6-8 weeks of adding bupropion, as modification of treatment should occur if adequate response is not achieved within this timeframe. 1
Begin monitoring within 1-2 weeks of initiation for adverse effects and therapeutic response. 1
Important Caveats
Contraindications to Consider
Do not use bupropion in patients with seizure disorders or those at increased seizure risk. 1
Avoid in agitated patients, as bupropion tends to be activating rather than sedating. 1
To minimize insomnia risk, administer the second daily dose before 3 PM if using twice-daily formulation. 1
Monitoring Requirements
Monitor closely for increases in suicidal thoughts and behaviors, particularly in the first 1-2 months, as this risk is greater during early treatment phases. 1
Watch for emergence of agitation, irritability, or unusual behavioral changes. 1
Pharmacologic Advantages
Bupropion has a different mechanism of action (dopamine/norepinephrine reuptake inhibition) compared to desvenlafaxine (serotonin/norepinephrine reuptake inhibition), providing complementary neurotransmitter effects. 1
Desvenlafaxine has minimal impact on cytochrome P450 enzyme systems, reducing the risk of pharmacokinetic drug interactions when combined with bupropion. 5
Bupropion is associated with lower rates of sexual adverse events compared to SNRIs, potentially offsetting sexual side effects from desvenlafaxine. 1