FDA-Approved Medications for Bipolar Depression
The FDA-approved medications for the treatment of bipolar depression are olanzapine-fluoxetine combination (OFC), quetiapine monotherapy, lurasidone (both as monotherapy and as adjunct to lithium or divalproex), and cariprazine. 1, 2
First-Line FDA-Approved Options
- Olanzapine-fluoxetine combination (OFC) is FDA-approved for the treatment of depressive episodes associated with bipolar I disorder 3
- Quetiapine monotherapy is FDA-approved for acute treatment of bipolar depression 1
- Lurasidone is FDA-approved both as monotherapy and as an adjunct to lithium or divalproex for bipolar depression 1, 2
- Cariprazine has received FDA approval for bipolar depression 2
Clinical Considerations for Medication Selection
- The overall effect size of OFC, quetiapine, and lurasidone in reducing depressive symptoms is similar 1
- OFC and quetiapine are associated with significant weight gain, metabolic disruption, and sedation 1
- Lurasidone has a minimal propensity for weight gain and is metabolically neutral, which is a clinically significant advantage 1
- When selecting medications, consider the patient's vulnerability to side effects and personal preferences 2
Additional Treatment Options with Evidence
- Lamotrigine has compelling evidence as an adjunct to lithium and for recurrence prevention in bipolar depression, though it is not FDA-approved specifically for acute bipolar depression 1, 2
- Lithium has established efficacy for maintenance treatment of bipolar disorder and specifically for suicide prevention 2, 4
- Valproic acid may be effective for bipolar depression, but has a very small evidence base 2, 4
Special Considerations
- Antidepressant monotherapy is contraindicated in bipolar I depression due to risk of mood destabilization 5, 6
- If antidepressants are used, they should always be in combination with a mood stabilizer or antimanic agent 5, 4
- Bupropion and SSRIs are preferred if an antidepressant is needed for breakthrough depression 6
- Electroconvulsive therapy (ECT) remains the first-line option for patients requiring urgent treatment of severe bipolar depression 2, 7
Common Pitfalls to Avoid
- Using antidepressant monotherapy in bipolar depression can trigger manic episodes or rapid cycling 5, 4
- Failure to monitor for metabolic side effects, particularly with OFC and quetiapine 1
- Inadequate duration of maintenance therapy, which should continue for at least 12-24 months after the acute episode 5
- Overlooking the importance of psychoeducation and psychosocial interventions as adjuncts to pharmacotherapy 5, 7