Abstract
Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.
Highlights
Antidepressant medications are commonly used to treat several mood and anxiety disorders such as major depressive disorder (MDD), obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD), and social anxiety disorder
In this systematic review and meta-analysis, the L allele of the 5-HTTLPR polymorphism was shown to be associated with better antidepressant response in patients with non-MDD psychiatric disorders and improved tolerability among individuals with any psychiatric diagnosis
These findings were most robust for individuals with European ancestry and those who were treated with selective serotonin reuptake inhibitors (SSRIs) and may be stronger in females. 4.1. 5-HTTLPR and Antidepressant Response
Summary
Antidepressant medications are commonly used to treat several mood and anxiety disorders such as major depressive disorder (MDD), obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD), and social anxiety disorder. Decision support tools have been developed to assist physicians’ prescribing decisions based on an individual’s genotype [4] In psychiatry, these pharmacogenetic-guided “decision support tools” have primarily included genes involved in antidepressant pharmacokinetics (e.g., cytochrome P450 genes). These pharmacogenetic-guided “decision support tools” have primarily included genes involved in antidepressant pharmacokinetics (e.g., cytochrome P450 genes) This is due to their established relationships with drug exposure, implications for dosing, and the availability of dosing guidelines developed by expert groups such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) [5,6]. Contrary findings have been published [22], and consensus on whether it is clinically useful to genotype the rs25531 variant in combination with the 5-HTTLPR polymorphisms has not been reached
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