Pharmacokinetic evaluation of olanzapine + fluoxetine for the treatment of bipolar depression

Introduction: A proprietary combination of the atypical antipsychotic drug olanzapine and the serotonin reuptake inhibitor fluoxetine (OFC, Symbyax) was approved for the treatment of bipolar depression based on a double-blind, placebo-controlled comparison of olanzapine, OFC, and placebo. Areas covered: This review considers published controlled and uncontrolled studies of the efficacy, pharmacodynamics, pharmacokinetics, interactions, and adverse effects of OFC. Beyond previously reviewed efficacy studies, an open-label 7-week study of 161 bipolar depressed patients (93% bipolar I), and an 8-week double-blind study of 833 bipolar I depressed patients with an open-label extension were identified. The structure and limitations of clinical trials of OFC are critically addressed. Expert opinion: OFC trades simplicity of administration for loss of flexibility of dosing and lack of a generic preparation, both of which are available for olanzapine and fluoxetine separately. Clinical trials are limited by short-term follow-up, exclusive use of symptom rating scale scores, limitation of subjects to those with depression that is not overly complex or comorbid, lack of consideration of subsyndromal hypomania and mood cycling, and high dropout rates. In the absence of comparisons to mood stabilizers combined with each other and/or antidepressants, the role of OFC in the treatment of bipolar depression remains unclear.