What are the options for augmenting Wellbutrin (bupropion) in patients who have not responded adequately to treatment?

Augmentation Strategies for Inadequate Response to Bupropion

For patients who have not responded adequately to bupropion treatment, the most evidence-based augmentation strategies include adding an atypical antipsychotic, switching to cognitive therapy, or augmenting with cognitive therapy. 1

First-Line Augmentation Options

Atypical Antipsychotics

• Aripiprazole: FDA-approved as adjunctive therapy for clinical depression
  • Dosing: Start at 2.5-10 mg/day 2
  • Benefits: Rapid improvement in depressive symptoms, with effects sustained for at least 4 months in clinical studies 2
  • Evidence: Multiple clinical trials show approximately two-fold higher remission rates compared to placebo when added to antidepressants 3
  • Monitoring: Watch for akathisia (may respond to dose reduction) and insomnia 2

Psychotherapy Options

• Cognitive Behavioral Therapy (CBT)
  • Strong evidence for effectiveness when added to pharmacotherapy 4
  • Associated with fewer adverse effects than medications alone
  • Lower relapse rates compared to medication monotherapy 4

Second-Line Augmentation Options

SSRI/SNRI Combinations

• Adding an SSRI to bupropion:
  • Combines different neurotransmitter mechanisms (bupropion affects norepinephrine/dopamine while SSRIs affect serotonin) 4
  • May help address symptoms not responding to bupropion alone
  • Caution: Monitor for drug interactions as bupropion inhibits CYP2D6, which metabolizes many SSRIs 5
  • Evidence suggests this combination can boost antidepressant response 6

Other Medication Options

• Buspirone, stimulants, thyroid hormone, or lithium can be considered as augmentation strategies 7
• Switching to another antidepressant is a reasonable alternative if augmentation is unsuccessful 1

Monitoring and Follow-Up

• Regular assessment: Begin monitoring within 1-2 weeks of initiating augmentation therapy 1
• Safety monitoring: Particularly important with atypical antipsychotics (metabolic parameters) and combination therapies
• Adequate trial: Allow 6-8 weeks to determine effectiveness of the augmentation strategy 1
• Dose adjustments: May be necessary when combining medications due to drug interactions 5

Important Considerations

• Drug interactions: Bupropion is primarily metabolized by CYP2B6 and is a CYP2D6 inhibitor, which can affect levels of many medications 5
• Seizure risk: Use caution when combining bupropion with other medications that lower seizure threshold 5
• Sexual dysfunction: If sexual side effects are a concern with SSRI augmentation, bupropion is actually associated with lower rates of sexual dysfunction than many other antidepressants 1

Treatment Algorithm

1. First attempt: Add aripiprazole (2.5-5 mg/day) or initiate cognitive therapy
2. If partial response: Optimize dose of augmentation agent
3. If no response after 6-8 weeks: Consider switching to a different antidepressant or trying a different augmentation strategy
4. For treatment-resistant cases: Consider combination of pharmacological and non-pharmacological approaches

The American College of Physicians guidelines emphasize that the most important decision is simply to try a different evidence-based approach when patients do not respond adequately to initial antidepressant treatment 1.