Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression

Roy H. Perlis, David H. Adams, Bonnie Fijal, Virginia K. Sutton, Mark Farmen, Alan Breier, John P. Houston

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)599-605
Number of pages7
JournalJournal of Clinical Psychiatry
Volume71
Issue number5
DOIs
StatePublished - May 2010

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Genetic Association Studies
olanzapine
Bipolar Disorder
Single Nucleotide Polymorphism
Fluoxetine
Genotype
Genes
Receptor, Melanocortin, Type 2
Dopamine D3 Receptors
Depression
Histamine H1 Receptors
Dopamine Agents
Dopamine D2 Receptors
Glucocorticoid Receptors
Therapeutics
Mixed Function Oxygenases
Double-Blind Method
Antidepressive Agents
Antipsychotic Agents
Dopamine

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression. / Perlis, Roy H.; Adams, David H.; Fijal, Bonnie; Sutton, Virginia K.; Farmen, Mark; Breier, Alan; Houston, John P.

In: Journal of Clinical Psychiatry, Vol. 71, No. 5, 05.2010, p. 599-605.

Research output: Contribution to journalArticle

Perlis, Roy H. ; Adams, David H. ; Fijal, Bonnie ; Sutton, Virginia K. ; Farmen, Mark ; Breier, Alan ; Houston, John P. / Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression. In: Journal of Clinical Psychiatry. 2010 ; Vol. 71, No. 5. pp. 599-605.
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