What medications are approved for bipolar depression?

Medications Approved for Bipolar Depression

For bipolar depression, olanzapine-fluoxetine combination, quetiapine, lurasidone, and cariprazine are FDA-approved treatments, with olanzapine-fluoxetine combination showing the strongest evidence for efficacy. 1, 2

FDA-Approved Medications for Bipolar Depression

First-Line Options:

1. Olanzapine-Fluoxetine Combination (OFC)

   • FDA-approved for bipolar depression 2
   • Ranked highest for effect size and response rate in comparative studies 3
   • Should be considered first-line treatment due to superior efficacy 3
   • Requires monitoring for metabolic side effects (weight gain, lipid abnormalities)

2. Quetiapine

   • FDA-approved for bipolar depression
   • Strong efficacy evidence 3
   • Associated with significant weight gain and metabolic side effects 1
   • Lower risk of switching to mania compared to other options 3

3. Lurasidone

   • FDA-approved for bipolar depression (monotherapy or adjunctive with lithium/valproate) 4
   • Ranked second for response rate 3
   • Well-tolerated with minimal metabolic effects 4
   • Common side effects: akathisia, extrapyramidal symptoms, somnolence 4
   • Take with food to ensure maximal absorption 4

4. Cariprazine

   • FDA-approved for bipolar depression 5
   • Emerging evidence of efficacy for bipolar depression, including with mixed features 5

Adjunctive and Alternative Options

Mood Stabilizers:

• Lithium

  • First-line treatment for bipolar disorder overall 1
  • Limited evidence specifically for bipolar depression 5
  • May reduce suicide risk in bipolar disorder 5

• Lamotrigine

  • Evidence for long-term benefit in preventing depressive episodes 5
  • Limited acute antidepressant efficacy
  • Better tolerated metabolically than many alternatives

• Valproate

  • Recommended as first-line for bipolar disorder 1
  • Limited evidence specifically for bipolar depression 5
  • Carries significant teratogenic risk 5

Antidepressants:

• Should ALWAYS be used in combination with mood stabilizers (lithium or valproate) 1
• Preferably SSRIs like fluoxetine 1
• Tricyclic antidepressants should be avoided due to risk of triggering mania 1
• Bupropion may be preferred alongside SSRIs for bipolar depression 6
• Controversy remains regarding efficacy and risk of switching to mania 6

Medications to Avoid for Bipolar Depression

• Aripiprazole: Limited or no therapeutic activity in bipolar depression 3
• Ziprasidone: Limited efficacy for bipolar depression despite low switch risk 3
• Risperidone: No evidence of efficacy for bipolar depression 3
• MAOIs: Limited therapeutic activity in bipolar depression 3

Monitoring and Management

• Regular monitoring required for:

  • Mood symptoms and suicidal ideation
  • Weight, BMI, blood pressure
  • Fasting glucose and lipid panels
  • Medication-specific parameters (e.g., lithium levels)

• For medications with metabolic concerns (olanzapine, quetiapine):

  • Consider switching to weight-neutral options if significant weight gain occurs 1
  • Patients may lose weight when switched from weight-gain-prone antipsychotics to weight-neutral options 1

Common Pitfalls to Avoid

1. Using antidepressants without mood stabilizers - This significantly increases risk of switching to mania 1

2. Underestimating suicide risk - Bipolar depression carries high suicide risk (20× general population) 5

3. Neglecting metabolic monitoring - Especially important with olanzapine and quetiapine 1

4. Relying solely on pharmacotherapy - Psychoeducation, cognitive behavioral therapy, and family interventions should be considered 1

5. Inadequate follow-up - Close monitoring is essential, particularly during medication changes 1