Baseline platelet serotonin in a multi-site treatment study of depression in veterans administration patients: Distribution and effects of demographic variables and serotonin reuptake inhibitors

J Affect Disord. 2023 Apr 14:327:368-377. doi: 10.1016/j.jad.2023.02.017. Epub 2023 Feb 6.

Abstract

Background: The objectives of the study were: (1) to examine the overall distribution of baseline platelet serotonin (5-hydroxytryptamine, 5-HT) values in patients seeking treatment for depression and to define subgroups based on the apparent presence or absence of drug exposure; (2) to assess the bioeffect of 5-HT reuptake inhibitors (SRIs) at the platelet 5-HT transporter; and (3) to examine the relationships of demographic variables including population (ancestry), sex, age, and season of sampling to platelet 5-HT concentration.

Methods: Platelet 5-HT levels were measured in a cross-sectional study of 1433 Veterans Administration (VA) patients participating in a pragmatic multi-site pharmacogenomic treatment study of depression. Patients were characterized medically and demographically using VA health records and self-report.

Results: A clearly bimodal distribution was observed for platelet 5-HT levels with the lower mode associated with patients exposed to SRIs at baseline. Median transporter blockade bioeffects were similar across the various selective 5-HT reuptake inhibitors (SSRIs) and 5-HT/norepinephrine reuptake inhibitors (SNRIs). In a subset of patients apparently not exposed to an SRI, significant effects of population and sex were observed with group mean platelet 5-HT levels being 25 % greater (p < 0.001) in African-American (AA) individuals compared to European-Americans (EAs). The female group mean was 14 % (p < 0.001) greater than male group mean. An effect of age was observed (r = -0.11, p < 0.001) and no effect of season or month of sampling was seen.

Conclusions: Further research is warranted to understand the bases and clinical implications of the population and sex differences. The apparent similarity in bioeffect at the 5-HT transporter across SSRIs and when comparing SSRIs and SNRIs informs discussions about initiating, dose adjustment and switching of 5-HT reuptake inhibitors.

Keywords: Depression; Platelet; Selective serotonin reuptake inhibitor (SSRI); Serotonin; Serotonin reuptake inhibitor (SRI); Veterans.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cross-Sectional Studies
  • Demography
  • Depression / drug therapy
  • Female
  • Humans
  • Male
  • Membrane Transport Proteins
  • Selective Serotonin Reuptake Inhibitors*
  • Serotonin
  • Serotonin and Noradrenaline Reuptake Inhibitors*
  • United States
  • United States Department of Veterans Affairs

Substances

  • Selective Serotonin Reuptake Inhibitors
  • Serotonin
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Membrane Transport Proteins