What is the olanzapine (atypical antipsychotic) and fluoxetine (selective serotonin reuptake inhibitor (SSRI)) combination, known by the brand name Symbyax, used for in the treatment of bipolar I disorder in adult patients?

Olanzapine-Fluoxetine Combination (Symbyax) for Bipolar I Disorder

The olanzapine-fluoxetine combination, marketed as Symbyax, is FDA-approved specifically for treating depressive episodes associated with bipolar I disorder in adults. 1

FDA-Approved Indications

The combination of olanzapine and fluoxetine has two distinct FDA-approved uses:

• Treatment of depressive episodes associated with bipolar I disorder in adult patients 1
• Treatment of treatment-resistant depression (major depressive disorder in patients who fail two separate antidepressant trials) 1

Critically, olanzapine monotherapy is NOT indicated for bipolar depression—the fluoxetine component is essential for this indication. 1

Clinical Evidence for Bipolar Depression

The American Academy of Child and Adolescent Psychiatry recommends olanzapine-fluoxetine combination as a first-line option for bipolar depression. 2

• The combination demonstrates superior efficacy compared to olanzapine monotherapy or lamotrigine for treating acute bipolar depression 3, 4
• Efficacy was established with the branded product Symbyax in clinical trials 1
• The combination improves depressive symptoms without increasing the risk of treatment-emergent mania 3, 4
• Long-term treatment for up to 24 weeks shows sustained efficacy with low risk of mania emergence (5.9%) and manageable depressive relapse rates (27.4%) 5

Why This Combination Works

Antidepressant monotherapy is explicitly contraindicated in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling. 2, 6

• The olanzapine component provides mood stabilization and prevents antidepressant-induced mania 3, 4
• The fluoxetine component addresses the depressive symptoms directly 3, 4
• This combination addresses both poles of bipolar disorder simultaneously—the atypical antipsychotic prevents mood destabilization while the SSRI treats depression 2

Available Formulations

Symbyax is available as a fixed-dose oral combination taken once daily, with the following strengths:

• 6 mg olanzapine/25 mg fluoxetine 7, 5
• 6 mg olanzapine/50 mg fluoxetine 7, 5
• 12 mg olanzapine/50 mg fluoxetine 7, 5

Important Safety Considerations

The combination carries metabolic risks typical of olanzapine, including weight gain and potential elevations in glucose, lipid, and prolactin levels. 3, 4

• The tolerability profile resembles olanzapine monotherapy more than fluoxetine monotherapy 7
• Baseline metabolic monitoring should include BMI, waist circumference, blood pressure, fasting glucose, and fasting lipid panel 2
• Follow-up monitoring includes monthly BMI for 3 months then quarterly, with blood pressure, glucose, and lipids at 3 months then yearly 2

Critical Clinical Pitfalls

• Never use fluoxetine or any SSRI as monotherapy in bipolar disorder—this dramatically increases risk of mania induction and rapid cycling 2, 6
• The fixed-dose formulation trades dosing flexibility for convenience—olanzapine and fluoxetine can be prescribed separately if dose adjustments are needed 8
• Maintenance therapy should continue for at least 12-24 months after achieving stability 2
• Among patients entering long-term treatment in remission, 62.5-66.7% maintained remission, supporting continued use 5