Systematic review of studies using platelet serotonin content to assess bioeffect of serotonin reuptake inhibitors at the serotonin transporter

Rationale Assessment of the bioeffect of serotonin reuptake inhibitors (SRIs, including both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)) at the serotonin transporter (SERT) in patients and healthy controls can have important theoretical and clinical implications. Objectives Bioeffect at SERT has been assessed by neuroimaging of brain SERT occupancy, through in vitro measurements of platelet serotonin (5-HT) uptake, and by measuring platelet 5-HT content pre- and post-initiation of SRI administration. Studies of platelet 5-HT content were reviewed in order to (1) determine the overall apparent bioeffect of SRIs; (2) compare bioeffect across types of SRIs; (3) compare the three approaches to assessing SRI bioeffect; and (4) determine how the findings might inform clinical practice. Methods We performed a systematic review of the published studies that measured platelet 5-HT content to assess SRI bioeffect at the platelet SERT. Studies using neuroimaging and in vitro platelet 5-HT uptake to assess SRI bioeffect were reviewed for comparison purposes. Results Clinical doses of SRIs typically resulted in 70-90% reductions in platelet 5-HT content. The observed bioeffect at the platelet SERT appeared similar among different SSRIs and SNRIs. The bioeffect estimations based on platelet 5-HT content were consistent with those obtained using neuroimaging to assess brain SERT occupancy and those based on the in vitro measurement of platelet 5-HT uptake. Conclusions In general, excellent agreement was seen in the apparent SRI bioeffect (70-90% inhibition) among the platelet 5-HT content studies and across the three bioeffect approaches. Theoretical and practical clinical implications are discussed.