From the Guidelines
Yes, Effexor (venlafaxine) and Wellbutrin (bupropion) can be used together, as evidenced by the STAR*D study, which reported similar efficacy of an augmentation of citalopram with bupropion SR, buspirone, or cognitive therapy 1. This combination is sometimes prescribed by healthcare providers for patients who haven't achieved adequate symptom relief with a single medication. The study found that within the medication groups, discontinuation because of adverse events was lower in the bupropion SR than in the buspirone augmentation group, suggesting that bupropion may be a safer option for augmentation 1. Key points to consider when using this combination include:
- Dosing varies based on individual needs, but common therapeutic doses range from 75-225 mg daily for Effexor and 150-450 mg daily for Wellbutrin.
- The combination works well mechanistically because these medications affect different neurotransmitters - Effexor primarily affects serotonin and norepinephrine, while Wellbutrin works on dopamine and norepinephrine.
- Potential side effects include increased blood pressure, anxiety, insomnia, and seizure risk, highlighting the need for close medical supervision and regular monitoring for side effects and drug interactions.
- The evidence from the STAR*D study and other trials suggests that this combination can be an effective strategy for patients who do not respond adequately to a single antidepressant treatment 1.
From the FDA Drug Label
Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors Therefore, coadministration of bupropion hydrochloride extended-release tablets (XL) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline)
- Key Considerations:
- Bupropion (Wellbutrin) is a CYP2D6 inhibitor.
- Venlafaxine (Effexor) is a substrate of CYP2D6.
- Co-administration of bupropion with venlafaxine may increase venlafaxine exposure.
- Clinical Decision:
- Effexor and Wellbutrin can be used together, but with caution.
- Consider dose reduction of venlafaxine when co-administered with bupropion.
- Monitor patient for increased exposure and potential side effects of venlafaxine 2.
From the Research
Combination Therapy of Effexor (Venlafaxine) and Wellbutrin (Bupropion)
- The combination of Effexor (venlafaxine) and Wellbutrin (bupropion) has been studied in various research papers, with some indicating its potential effectiveness in treating major depressive disorder (MDD) 3, 4.
- A case study published in 1999 reported the successful use of venlafaxine and bupropion combination therapy in a patient with treatment-resistant depression, with significant reduction in depressive symptoms and improvement in social function 4.
- However, another study published in 2004 reported a rare case of serotonin syndrome induced by the combination of bupropion and an SSRI, highlighting the potential risks of combining these medications 5.
- A review of the literature on combining bupropion with SSRIs or SNRIs found that the available data suggest that this combination is generally well tolerated and can boost antidepressant response, but additional randomized controlled studies are needed to answer important questions regarding optimal dose and duration of treatment 3.
Safety and Efficacy Considerations
- The combination of Effexor and Wellbutrin may increase the risk of serotonin syndrome, a potentially fatal complication of the combined use of agents that enhance serotonin activity 5.
- A systematic review and dose-response meta-analysis of second-generation antidepressants, including venlafaxine, found that the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression 6.
- When prescribing Effexor and Wellbutrin together, a risk-benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated 7.