Pharmacokinetic evaluation of olanzapine + fluoxetine for the treatment of
bipolar depression.
Author(s): Dubovsky SL.
Affiliation(s): Author information:
Department of Psychiatry, State University of New York at Buffalo, 462 Grider St,
Buffalo, NY 14215, USA. dubovsky@buffalo.edu
Publication date & source: 2013, Expert Opin Drug Metab Toxicol. , 9(2):207-14
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.
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