TY - JOUR
T1 - Pharmacogenomics of antidepressant induced mania
T2 - A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association
AU - Biernacka, Joanna M.
AU - McElroy, Susan L.
AU - Crow, Scott
AU - Sharp, Alexis
AU - Benitez, Joachim
AU - Veldic, Marin
AU - Kung, Simon
AU - Cunningham, Julie M.
AU - Post, Robert M.
AU - Mrazek, David
AU - Frye, Mark A.
N1 - 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.
PY - 2012/1
Y1 - 2012/1
N2 - 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).
AB - 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).
KW - Antidepressant
KW - Bipolar disorder
KW - Pharmacogenomics
KW - SLC6A4
UR - http://www.scopus.com/inward/record.url?scp=84857055178&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857055178&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2011.05.038
DO - 10.1016/j.jad.2011.05.038
M3 - Review article
C2 - 21680025
AN - SCOPUS:84857055178
SN - 0165-0327
VL - 136
SP - e21-e29
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
IS - 1-2
ER -