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

doi:10.1016/j.jad.2011.05.038

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

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Review article › peer-review

32 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	e21-e29
Journal	Journal of Affective Disorders
Volume	136
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jad.2011.05.038
State	Published - 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.

Keywords

Antidepressant
Bipolar disorder
Pharmacogenomics
SLC6A4

Access

10.1016/j.jad.2011.05.038

OpenUrl availability

Full text

Cite this

Biernacka, J. M., McElroy, S. L., Crow, S., Sharp, A., Benitez, J., Veldic, M., Kung, S., Cunningham, J. M., Post, R. M., Mrazek, D., & Frye, M. A. (2012). Pharmacogenomics of antidepressant induced mania: A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association. Journal of Affective Disorders, 136(1-2), e21-e29. https://doi.org/10.1016/j.jad.2011.05.038

Biernacka, JM, McElroy, SL, Crow, S, Sharp, A, Benitez, J, Veldic, M, Kung, S, Cunningham, JM, Post, RM, Mrazek, D & Frye, MA 2012, 'Pharmacogenomics of antidepressant induced mania: A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association', Journal of Affective Disorders, vol. 136, no. 1-2, pp. e21-e29. https://doi.org/10.1016/j.jad.2011.05.038

@article{51b7a9e7b4e541678521d22628d41486,

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

abstract = "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).",

keywords = "Antidepressant, Bipolar disorder, Pharmacogenomics, SLC6A4",

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

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. ",

year = "2012",

month = jan,

doi = "10.1016/j.jad.2011.05.038",

language = "English (US)",

volume = "136",

pages = "e21--e29",

journal = "Journal of Affective Disorders",

issn = "0165-0327",

publisher = "Elsevier B.V.",

number = "1-2",

}

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 -

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

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this