What is the next treatment option for a patient with treatment-resistant depression currently on 40mg vilazodone (Viibryd)?

Treatment-Resistant Depression: Next Steps After Viibryd Failure

The next treatment option is augmentation with aripiprazole (or another atypical antipsychotic such as quetiapine, brexpiprazole, or cariprazine) added to the current Viibryd regimen. 1, 2, 3

Confirming Treatment-Resistant Depression

This patient clearly meets criteria for treatment-resistant depression (TRD), defined as failure to respond to at least two adequate antidepressant trials with different mechanisms of action. 1, 2 The patient has failed:

• Multiple SSRIs (different mechanisms attempted)
• SNRIs (norepinephrine-serotonin reuptake inhibition)
• Bupropion (dopamine-norepinephrine reuptake inhibition)
• Augmentation attempts with both abilify (aripiprazole) and lithium
• Currently on vilazodone 40mg (maximum approved dose) 4

Critical verification step: Ensure each prior trial was at minimum effective dosage for at least 4 weeks before counting it as a treatment failure. 5, 1 Discontinuation due to side effects before completing 4 weeks should not count as treatment failure. 5, 1

Primary Recommendation: Atypical Antipsychotic Augmentation

Why This Is First-Line

Augmentation with atypical antipsychotics is the primary first-line FDA-approved strategy after inadequate response to at least one antidepressant at adequate dose for ≥4 weeks. 1, 2, 3 The evidence base supporting atypical antipsychotics (aripiprazole, quetiapine, brexpiprazole, cariprazine, and olanzapine) is the most extensive and rigorous of all pharmacological approaches in TRD. 2, 6, 7

Specific Agent Selection

Aripiprazole augmentation is the most studied option, being the first medication approved by the FDA specifically as adjunctive therapy for treatment-resistant depression. 2, 7 However, since this patient has already tried abilify (aripiprazole) previously, consider:

• Quetiapine extended-release: Particularly beneficial if comorbid anxiety or insomnia are present 7
• Brexpiprazole or cariprazine: FDA-approved alternatives with similar efficacy 6
• Olanzapine-fluoxetine combination: FDA-approved specifically for TRD, starting dose 5mg olanzapine with 20mg fluoxetine once daily in the evening, dose range 5-20mg olanzapine with 20-50mg fluoxetine 2

Important Caveat About Prior Aripiprazole Trial

The patient previously tried abilify, but the context matters: Was it used as augmentation to an adequate antidepressant trial, or was it tried in a different context? If it was not used as augmentation to Viibryd specifically, trying aripiprazole again as augmentation to the current Viibryd regimen remains reasonable. 1

Monitoring Requirements

Metabolic monitoring is essential when using atypical antipsychotics. 2 Benefits must be weighed against potential adverse events including:

• Weight gain
• Akathisia
• Tardive dyskinesia
• Metabolic dysregulation 6

Alternative Augmentation Strategies

If atypical antipsychotics are contraindicated, not tolerated, or the patient declines:

Second-Line Pharmacological Options

Alternative augmentation strategies with strong evidence include: 2

• Lithium (already tried by this patient)
• Liothyronine (T3) 2
• Lamotrigine 2
• Combination with bupropion (already tried as monotherapy, but could be added as augmentation) 2
• Tricyclics or mirtazapine 2

Highly Refractory Cases

Esketamine/ketamine is recommended for highly refractory cases and may help reduce suicidal ideation, but is typically reserved for patients who have failed multiple augmentation strategies. 1, 2, 3 This patient may be approaching this threshold given the extensive treatment history.

Non-Pharmacological Options

Transcranial magnetic stimulation (TMS) should be considered for patients who have failed medication trials. 1, 3 This is particularly appropriate given this patient's extensive pharmacological treatment failures.

Cognitive behavioral therapy should be used in conjunction with pharmacotherapy throughout treatment. 1

Common Pitfalls to Avoid

• Do not switch antidepressants again without augmentation first. Switching to vilazodone from citalopram in partial responders showed no advantage over dose escalation, suggesting that switching alone has limited benefit in TRD. 8
• Do not exclude this patient from treatment trials based solely on number of prior medication failures. Multiple-drug resistant individuals should not be excluded from TRD treatment strategies. 5, 3
• Do not count the lithium and aripiprazole trials as failures if they were not given adequate duration (≥4 weeks) or if discontinued due to side effects before 4 weeks. 5, 1

Practical Algorithm

1. Verify adequate trials: Confirm each prior medication was at minimum effective dose for ≥4 weeks 1, 3
2. Continue Viibryd 40mg (already at maximum dose) 4
3. Add atypical antipsychotic augmentation: Start with quetiapine extended-release, brexpiprazole, or cariprazine (since aripiprazole was previously tried) 2, 6, 7
4. If augmentation fails or not tolerated: Consider TMS 1, 3 or esketamine for highly refractory cases 1, 2
5. Maintain concurrent psychotherapy throughout treatment 1