What medications are FDA (Food and Drug Administration)-approved to treat bipolar depression?

FDA-Approved Medications for Bipolar Depression

The FDA-approved medications for treating bipolar depression are olanzapine-fluoxetine combination (OFC), quetiapine (immediate or extended release), and lurasidone (as monotherapy or adjunct to lithium/valproate). 1

FDA-Approved Options and Their Evidence

First-Line Treatment Options:

1. Olanzapine-Fluoxetine Combination (OFC)

   • FDA-approved for bipolar depression in adults 2
   • Effective for acute treatment of bipolar depression 1
   • Limitations: Significant weight gain (NNH of 6 for ≥7% weight gain) and metabolic disruption 3
   • Side effects include diarrhea (NNH of 9) 3

2. Quetiapine (immediate or extended release)

   • FDA-approved for bipolar depression 1
   • Available in both immediate and extended-release formulations 4
   • Effective at doses of 300mg/day or 600mg/day with no significant difference between doses 4
   • Limitations: Sedation (NNH of 3), dry mouth (NNH of 4), and moderate weight gain (NNH of 16 for ≥7% weight gain) 3
   • Only atypical antipsychotic approved for both bipolar mania and depression 5
   • Also effective for maintenance therapy in preventing mood episode recurrence 4

3. Lurasidone

   • FDA-approved for bipolar depression as both monotherapy and adjunctive therapy with lithium or valproate 1
   • Metabolically neutral with minimal propensity for weight gain (NNH of 58 for ≥7% weight gain as monotherapy) 3
   • No NNH values less than 10 for common adverse events compared to placebo 3

Treatment Selection Algorithm

Step 1: Assess patient risk factors and priorities

• Weight gain/metabolic risk concerns → Consider lurasidone
• Sedation concerns → Avoid quetiapine
• History of rapid cycling or antidepressant-induced mania → Avoid OFC as initial therapy

Step 2: Select appropriate medication based on specific patient factors

• For patients with metabolic concerns: Lurasidone is preferred due to metabolic neutrality
• For patients needing rapid response: Quetiapine or OFC may be considered despite side effect risks
• For patients on lithium or valproate with inadequate response: Add lurasidone as adjunctive therapy

Step 3: Dosing considerations

• Quetiapine: 300mg/day is as effective as 600mg/day with potentially fewer side effects 4
• Lurasidone: Effective as both monotherapy and adjunctive therapy
• OFC: Fixed combination of olanzapine and fluoxetine

Important Clinical Considerations

Efficacy Comparison

All three FDA-approved treatments have similar efficacy profiles with NNTs for response and remission ranging from 4-7 3, but differ significantly in their side effect profiles.

Avoiding Common Pitfalls

1. Misdiagnosis risk: Up to 64% of depression encounters occur in primary care, with frequent misdiagnosis of bipolar depression as unipolar depression 6

2. Antidepressant monotherapy risk: Standard antidepressants (SSRIs, SNRIs) are not FDA-approved for bipolar depression and may cause:

   • Treatment-emergent mania/hypomania
   • Rapid cycling
   • Increased suicidality 6

3. Monitoring requirements:

   • For OFC and quetiapine: Regular monitoring of weight, metabolic parameters
   • For all medications: Assessment of treatment response within 6-8 weeks 2

Maintenance Considerations

• Quetiapine has demonstrated efficacy in maintenance treatment for preventing recurrence of mood episodes 4
• Patients who respond to acute treatment should continue therapy for at least 4-9 months 2

By selecting from these FDA-approved options and carefully considering individual risk factors, clinicians can optimize treatment outcomes while minimizing adverse effects in patients with bipolar depression.