Serotonin transporter genetic variation and antidepressant response and tolerability: A systematic review and meta-analysis

Kiera Stein, Abdullah Al Maruf, Daniel J. Müller, Jeffrey R. Bishop, Chad A. Bousman

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Article number1334
JournalJournal of Personalized Medicine
Issue number12
StatePublished - Dec 2021

Bibliographical note

Funding Information:
Acknowledgments: C.B. is supported by the Cumming School of Medicine and Alberta Children’s Hospital Foundation. A.M. is supported by the College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • 5-HTTLPR
  • Antidepressant
  • Efficacy
  • Genotype
  • Pharmacogenetics
  • SLC6A4
  • Tolerability


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