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.

Anderson GM, Ramsey CM, Lynch KG, Gelernter J, Oslin DW. 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. Journal of affective disorders. 2023 Apr 14; 327:368-377.

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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.