Daray FM, Thommi SB, Ghaemi SN. The pharmacogenetics of antidepressant-induced mania: a systematic review and meta-analysis. Bipolar Disord 12: 702-706

Hospital Neuropsiquiátrico Braulio A. Moyano, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Bipolar Disorders (Impact Factor: 4.97). 11/2010; 12(7):702-6. DOI: 10.1111/j.1399-5618.2010.00864.x
Source: PubMed


Antidepressant-induced mania (AIM) has been associated with the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism in some studies but not in others. We conducted a meta-analysis of those studies and other studies of genetic predictors of AIM.
MEDLINE-based searches of genetic studies of AIM were conducted, and a meta-analysis of six studies of 5-HTTLPR was performed. Other polymorphisms were insufficiently studied to allow for meta-analysis.
There was an association of the short (s) variant of 5-HTTLPR and AIM [risk ratio (RR) = 1.35, 95% confidence interval (CI): 1.04-1.76, p=0.02]. There was a higher frequency of s carriers (sl and ss genotypes) in those who developed AIM [RR = 1.38, 95% CI: 0.98-1.93), p=0.06].
The 5-HTTLPR polymorphism appears to have a moderate effect size association with AIM in patients with bipolar disorder.

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    • "Adolescents who have not manifested the manic component of a bipolar disorder may be particularly vulnerable to SSRI antidepressant-induced mania or hypomania (Frye et al., 2009). Although preliminary studies showed conflicting results regarding the association between 5-HTTLPR polymorphism and antidepressant-induced mania (Mundo et al., 2001; Rousseva et al., 2003; Serretti et al., 2004; Baumer et al., 2006; Masoliver et al., 2006; Ferreira Ade et al., 2009), a recent meta-analysis indicated a higher incidence of antidepressant-induced mania in patients with the “s” variant of 5-HTTLPR (Daray et al., 2010). Likelihood of SSRI monotherapy response is deemed low once failure of the “SSRI challenge” test has been observed in this category. "
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