Adjunctive Antidepressant Therapy with Desvenlafaxine
Bupropion is the recommended antidepressant to use as an adjunct to desvenlafaxine for treatment-resistant depression. 1
Evidence for Bupropion Combination
The combination of desvenlafaxine (or its parent compound venlafaxine) with bupropion provides complementary mechanisms of action that can convert partial response to full response in treatment-resistant cases:
Bupropion combined with venlafaxine (the parent compound of desvenlafaxine) has demonstrated synergistic effects in reducing depressive symptoms and significantly increasing social function in patients unresponsive to various antidepressant classes 1
This combination acts through distinct neurotransmitter pathways: desvenlafaxine inhibits serotonin and norepinephrine reuptake, while bupropion primarily affects dopamine and norepinephrine through different mechanisms 2, 1
The pharmacokinetic profile supports this combination, as desvenlafaxine has minimal CYP450 metabolism (primarily glucuronidation) and bupropion is metabolized differently, reducing risk of drug-drug interactions 2, 3
Dosing Strategy
When combining these agents:
Start desvenlafaxine at 50 mg daily and titrate to 100 mg if needed, as doses above 100 mg show no additional therapeutic benefit but increased side effects 3, 4
Add bupropion gradually, titrating up to 100 mg three times daily (or equivalent extended-release formulation) over several months while monitoring response 1
Allow 4-8 weeks minimum to assess therapeutic response before making further adjustments 5
Alternative Considerations
If bupropion is contraindicated or not tolerated:
Mirtazapine may be considered as it has a different receptor profile and can address residual insomnia or appetite issues, though this combination lacks specific published evidence 5
Tricyclic antidepressants (nortriptyline or desipramine) could theoretically augment SNRI therapy, but carry higher risk of adverse effects including anticholinergic effects and cardiac conduction issues, particularly in older adults 5
Important Caveats
Monitor for serotonin syndrome when combining any serotonergic agents, though risk is lower with bupropion than with other combinations 2
Bupropion is contraindicated in patients with seizure disorders or eating disorders due to increased seizure risk 5
The combination may cause activating effects (nervousness, insomnia), so consider timing of doses and potentially giving bupropion before 3 PM 5
Sexual dysfunction is less common with bupropion compared to SSRIs, making it advantageous when desvenlafaxine causes sexual side effects 5