scholarly journals Pediatric Therapeutic Drug Monitoring for Selective Serotonin Reuptake Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Jeffrey R. Strawn ◽  
Ethan A. Poweleit ◽  
Chakradhara Rao S. Uppugunduri ◽  
Laura B. Ramsey
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Depressive Disorders ◽  
Plasma Concentrations ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Therapeutic Drug ◽  
The Impact

Therapeutic drug monitoring (TDM) is uncommon in child and adolescent psychiatry, particularly for selective serotonin reuptake inhibitors (SSRIs)—the first-line pharmacologic treatments for depressive and anxiety disorders. However, TDM in children and adolescents offers the opportunity to leverage individual variability of antidepressant pharmacokinetics to shed light on non-response and partial response, understand drug-drug interactions, evaluate adherence, and characterize the impact of genetic and developmental variation in pharmacokinetic genes. This perspective aims to educate clinicians about TDM principles and examines evolving uses of TDM in SSRI-treated youths and their early applications in clinical practice, as well as barriers to TDM in pediatric patients. First, the impact of pharmacokinetic genes on SSRI pharmacokinetics in youths could be used to predict tolerability and response for some SSRIs (e.g., escitalopram). Second, plasma concentrations are significantly influenced by adherence, which may relate to decreased efficacy. Third, pharmacometric analyses reveal interactions with proton pump inhibitors, oral contraceptives, cannabinoids, and SSRIs in youths. Rapid developments in TDM and associated modeling have enhanced the understanding of variation in SSRI pharmacokinetics, although the treatment of anxiety and depressive disorders with SSRIs in youths often remains a trial-and-error process.

scholarly journals The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis

2019 ◽  
Vol 4 (2) ◽  
pp. 144-152 ◽  
Author(s):  
Melanie P Jensen ◽  
Oliver J Ziff ◽  
Gargi Banerjee ◽  
Gareth Ambler ◽  
David J Werring
Keyword(s):  
Serotonin Reuptake ◽  
Observational Studies ◽  
Intracranial Haemorrhage ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Meta Analysis ◽  
Serotonin Reuptake Inhibitors ◽  
Quality Data ◽  
Selective Serotonin ◽  
Increased Risk ◽  
The Impact

Introduction Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRIs). We sought to clarify the impact of SSRIs on ICrH, accounting for study methodology. Patients and methods A comprehensive search of Medline, Embase and the Cochrane Library from 1960 to December 2017 identified studies comparing SSRIs with control. The outcomes (first-ever and recurrent ICrH) were meta-analysed using a random effects model. Results Twenty-four observational studies and three randomised trials were available for meta-analysis, totalling 4,844,090 patient-years of follow-up. Those receiving SSRIs were more likely to be female ( p = 0.01) and have depression ( p < 0.001). Compared to controls, SSRI users had a significantly increased risk of ICrH (relative risk (RR) 1.26, 95%CI 1.11–1.42). Although SSRI use was associated with increased ICrH risk in those without previous ICrH (RR 1.31, 95%CI 1.15–1.48), this was not the case in those with previous ICrH (RR 0.95, 95%CI 0.83–1.09). Sensitivity analysis according to the bleeding definition reported demonstrated that although ‘haemorrhagic stroke’ was associated with SSRIs (RR 1.40, 95%CI 1.13–1.72), intracerebral haemorrhage was not (RR 1.11, 95%CI 0.86–1.42). Additional sensitivity analyses demonstrated a stronger association between SSRIs and ICrH in studies with a high ( p < 0.001) compared to low risk of bias ( p = 0.09) and with retrospective ( p < 0.001) compared to prospective (p=0.31) study designs. Discussion Although SSRIs are associated with an increased risk of ICrH, the association is partly accounted for by important biases and other methodological limitations in the available observational data. Conclusion Our findings suggest there is insufficient high-quality data to advise restriction of SSRIs because of concern regarding ICrH risk.

scholarly journals Use of selective serotonin reuptake inhibitors is associated with very low plasma-free serotonin concentrations in humans

2019 ◽  
Vol 57 (1) ◽  
pp. 59-63
Author(s):  
Marloes AM Peters ◽  
Martijn van Faassen ◽  
Wilhelmina HA de Jong ◽  
Grietje Bouma ◽  
Coby Meijer ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Serotonin Reuptake ◽  
High Speed ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Plasma Concentrations ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Blood Collection ◽  
Plasma Tryptophan ◽  
Platelet Serotonin

Background Selective serotonin reuptake inhibitors (SSRIs) block the serotonin transporter on neurons, but also on platelets, thus decreasing platelet serotonin concentrations in users of SSRIs. Data on plasma-free serotonin concentrations in SSRI users are lacking, while plasma-free serotonin is available for receptor binding and plays a role in several pathophysiological processes. We therefore measured the plasma-free and platelet serotonin concentrations in users of SSRIs and age-matched healthy controls, and we analysed plasma concentrations of the serotonin precursor tryptophan and serotonin metabolite 5-hydroxyindoleamineacetic acid (5-HIAA). Methods For this cross-sectional single-centre case control study, participants were recruited at the departments of Psychiatry and General Medicine. High-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to measure plasma-free and platelet serotonin, plasma tryptophan and 5-HIAA concentrations. Preanalytical conditions were optimized by careful blood collection, rapid sample handling, high-speed centrifugation, drug and diet restrictions and age-matched controls. Results In 64 SSRI users, median concentrations of plasma-free and platelet serotonin were 10-fold and 14-fold lower, respectively, than in 64 matched controls. Patients using higher dose SSRIs or those with higher affinity for the serotonin transporter had lower plasma-free and platelet serotonin concentrations. Compared with controls, SSRI users had similar median plasma tryptophan concentrations but slightly higher plasma 5-HIAA concentrations. Conclusion SSRI users have low platelet serotonin and low plasma-free serotonin. This could not be explained by lower concentrations of its precursor tryptophan, and only partially by increased breakdown to 5-HIAA.

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