What can be added to Viibryd (vilazodone) for treatment-resistant depression?

Augmentation Options for Vilazodone (Viibryd) in Treatment-Resistant Depression

For patients with depression not responding adequately to vilazodone (Viibryd), augmentation with an atypical antipsychotic such as aripiprazole is the recommended first-line approach. 1, 2

Understanding Treatment-Resistant Depression

• Treatment-resistant depression (TRD) is defined as failure to respond to at least two antidepressant medications with different mechanisms of action, both administered at adequate doses for at least 4 weeks 3, 1
• An adequate trial requires the minimal approved dosage administered for at least four weeks to determine efficacy 3, 2
• Discontinuation due to side effects before completing four weeks should not be considered a treatment failure 3

Augmentation Strategies for Vilazodone

First-Line Options:

• Atypical antipsychotic augmentation:
  • Aripiprazole is recommended as first-line augmentation for patients who have failed to respond to vilazodone 1, 2
  • Approximately one-third of patients with SSRI-resistant depression show clinically meaningful response to atypical antipsychotic augmentation 1

Second-Line Options:

• Switch to an antidepressant with a different mechanism of action:

  • Consider switching to an SNRI such as venlafaxine or mirtazapine 1
  • Approximately 25% of patients achieve remission after switching to a different antidepressant 1
  • Bupropion is a unique option with norepinephrine and dopamine activity but no serotonergic effects, which may complement vilazodone's strong serotonergic profile 4

• Psychotherapy augmentation:

  • Cognitive Behavioral Therapy (CBT) has similar efficacy to medication augmentation but with lower discontinuation rates due to adverse events 1

Advanced Options for Highly Refractory Cases

• Neuromodulation therapies:

  • Transcranial magnetic stimulation (TMS) can be considered for patients who have failed multiple medication trials 2
  • Electroconvulsive therapy (ECT) should not be an exclusion criterion for future treatments 3

• Ketamine/esketamine:

  • Can be considered for highly refractory cases 2

Important Clinical Considerations

• Mechanism of action: Vilazodone is a dual-acting antidepressant that combines SSRI activity with 5-HT1A receptor partial agonism 5, 6
• Pharmacological complementarity: When augmenting vilazodone, consider agents with different mechanisms of action to provide complementary effects 1
• Adequate trial duration: Allow at least 4 weeks at therapeutic doses before determining efficacy of the augmentation strategy 3, 1
• Common side effects of vilazodone: Diarrhea, nausea, vomiting, and insomnia are most common, which may influence choice of augmentation agent 4, 7

Common Pitfalls to Avoid

• Inadequate dosing: Ensure vilazodone was given at therapeutic doses (40mg daily is recommended) before declaring treatment failure 4, 8
• Insufficient duration: Full therapeutic effect of vilazodone may take 4-6 weeks to manifest 4, 8
• Same mechanism augmentation: Avoid augmenting with agents that have highly overlapping mechanisms of action 1
• Ignoring previous treatment history: Consider all previous medication trials within the past two years when determining next steps 3, 2