What medication to add to Effexor (venlafaxine) when it's not controlling depression symptoms?

Augmentation Strategies for Venlafaxine in Treatment-Resistant Depression

When venlafaxine (Effexor) is not adequately controlling depression symptoms, adding aripiprazole has shown superior efficacy compared to bupropion augmentation, with remission rates of 55.4% versus 34.0%. 1

Evidence-Based Augmentation Options

First-Line Augmentation:

• Aripiprazole: Add 2-15mg daily
  • Provides significantly higher remission rates compared to bupropion augmentation (55.4% vs 34.0%) 1
  • Monitor for akathisia, weight gain, and metabolic changes

Alternative Augmentation Options:

1. Bupropion SR: 150-300mg daily

   • Can be effective but with lower remission rates than aripiprazole 1
   • Particularly useful when energy and motivation are lacking
   • Avoid in patients with seizure disorders or eating disorders

2. Mirtazapine: 15-45mg daily

   • Similar efficacy whether used as an augmentation strategy or as a switch strategy 1
   • Beneficial for patients with insomnia and poor appetite
   • Monitor for sedation and weight gain

Decision-Making Algorithm

1. Assess specific residual symptoms:

   • For anxiety symptoms: Consider aripiprazole (first choice) or mirtazapine
   • For fatigue/low energy: Consider bupropion SR
   • For insomnia: Consider mirtazapine

2. Evaluate comorbidities:

   • Seizure disorder: Avoid bupropion
   • Metabolic concerns: Use caution with aripiprazole and mirtazapine
   • Weight concerns: Prefer bupropion over mirtazapine

3. Consider dosing of current venlafaxine:

   • Ensure venlafaxine is optimized (up to 225-375mg daily) before augmentation 2
   • The mean effective dose in treatment-resistant depression is 260mg/day 2

Monitoring and Expectations

• Evaluate response to augmentation therapy after 2-3 weeks initially, then at 4-6 weeks for full effect 3
• Use standardized depression rating scales to objectively track progress
• Monitor for potential drug interactions, particularly serotonin syndrome with combinations of serotonergic agents

Important Considerations

• Approximately 38% of patients do not achieve treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1
• In the STAR*D trial, only about 1 in 4 patients became symptom-free after switching medications 1
• If augmentation strategies fail, consider switching to a different antidepressant class or consulting with a psychiatrist for more complex approaches

Clinical Pitfalls to Avoid

• Don't continue ineffective treatments too long; if no improvement after 4-6 weeks of augmentation, reconsider the approach
• Avoid combining multiple serotonergic agents without careful monitoring for serotonin syndrome
• Don't overlook the importance of optimizing the venlafaxine dose before adding augmentation
• Beware of potential drug interactions that may reduce efficacy or increase side effects