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Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder

Molecular Psychiatry volume 15, pages 473–500 (2010)Cite this article

Abstract

This systematic review summarizes pharmacogenetic studies on antidepressant response and side effects. Out of the 17 genes we reviewed, 8 genes were entered into the meta-analysis (SLC6A4, HTR1A, HTR2A, TPH1, gene encoding the β-3 subunit, brain-derived neurotrophic factor (BDNF), HTR3A and HTR3B). TPH1 218C/C genotype (7 studies, 754 subjects) was significantly associated with a better response (odds ratio, OR=1.62; P=0.005) with no heterogeneity between ethnicities. A better response was also observed in subjects with the Met variant within the BDNF 66Val/Met polymorphism (4 studies, 490 subjects; OR=1.63, P=0.02). Variable number of tandem repeats polymorphism within intron 2 (STin2) 12/12 genotype showed a trend toward a better response in Asians (STin2: 5 studies, 686 subjects; OR=3.89, P=0.03). As for side effects, pooled ORs of serotonin transporter gene promoter polymorphism (5-HTTLPR) l (9 studies, 2642 subjects) and HTR2A −1438G/G (7 studies, 801 subjects) were associated with a significant risk modulation (OR=0.64, P=0.0005) and (OR=1.91, P=0.0006), respectively. Interestingly, this significance became more robust when analyzed with side effect induced by selective serotonin reuptake inhibitors only (5-HTTLPR: P=0.0001, HTR2A: P<0.0001). No significant result could be observed for the other variants. These results were not corrected for multiple testing in each variant, phenotype and subcategory. This would have required a Bonferroni significance level of P<0.0023. Although some heterogeneity was present across studies, our finding suggests that 5-HTTLPR, STin2, HTR1A, HTR2A, TPH1 and BDNF may modulate antidepressant response.

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Acknowledgements

We thank Dr Toshihiko Kinoshita for his contribution. This study was supported in part by the Japanese Society of Clinical Pharmacology and Therapeutics, and Fondazione del Monte di Bologna e Ravenna.

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  1. Institute of Psychiatry, University of Bologna, Bologna, Italy

    M Kato & A Serretti

  2. Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan

    M Kato

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Kato, M., Serretti, A. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry 15, 473–500 (2010). https://doi.org/10.1038/mp.2008.116

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