Pharmacogenomics of antidepressant induced mania: A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association

Joanna M. Biernacka, Susan L. McElroy, Scott Crow, Alexis Sharp, Joachim Benitez, Marin Veldic, Simon Kung, Julie M. Cunningham, Robert M. Post, David Mrazek, Mark A. Frye

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Background: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. Methods: Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. Results: Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N = 340 AIM+ cases, N = 543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. Limitations: Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. Conclusions: There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).

Original languageEnglish (US)
Pages (from-to)e21-e29
JournalJournal of Affective Disorders
Issue number1-2
StatePublished - Jan 2012

Bibliographical note

Funding Information:
Funding for the study was provided by a gift from the Marriott Family. The Marriott family had no further role in the study design, analysis or interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.

Funding Information:
Dr. Crow is employed by the University of Minnesota and has received research support from Novartis.


  • Antidepressant
  • Bipolar disorder
  • Pharmacogenomics
  • SLC6A4


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