Genetic Association Study of Treatment Response With Olanzapine/Fluoxetine Combination or Lamotrigine in Bipolar I Depression
J Clin Psychiatry 2010;71(5):599-605
© Copyright 2014 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
Objective: To evaluate common genetic
variations for association with symptomatic
improvement in bipolar I depression following
treatment with olanzapine/fluoxetine combination (OFC) or lamotrigine.
Method: Symptom improvement was assessed in 88 OFC-treated and 85 lamotrigine-treated white patients with bipolar I depression in the 7-week acute period of a randomized, double-blind study comparing OFC (6/25, 6/50, 12/25, or 12/50 mg/d [olanzapine/fluoxetine]) with lamotrigine (titrated
to 200 mg/d). The original study was conducted from November 2003 to August 2004. Single nucleotide polymorphisms (SNPs) were genotyped in a set of 19 candidate genes corresponding to known sites of activity for olanzapine and fluoxetine or previously associated with antidepressant or antipsychotic response. Primary outcome was the reduction in Montgomery-Asberg Depression Rating Scale (MADRS) total score as assessed by the difference by genotype from baseline to week 7 from a mixed-effects repeated measures analysis with terms for visit, genotype, genotype-by-visit interaction, and baseline MADRS score as a covariate.
Results: SNPs within the dopamine D3 receptor and histamine H1 receptor (HRH1) genes were significantly associated with response to OFC. SNPs within the dopamine D2 receptor, HRH1, dopamine β-hydroxylase, glucocorticoid receptor, and melanocortin 2 receptor genes were significantly associated with response to lamotrigine.
Conclusions: SNPs in specific candidate genes were associated with symptomatic improvement in a treatment-specific fashion. These results suggest the importance of dopaminergic effects in the treatment of patients with bipolar I depression and the potential utility of genotyping in selection of pharmacologic treatments for bipolar depression.
Submitted: August 22, 2008; accepted January 2, 2009.
Online ahead of print: December 15, 2009.
Corresponding author: Roy H. Perlis, MD, MSc, Bipolar Clinic and Research Program, 50 Staniford St, 5th Floor, Boston, MA 02114