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Reporting of harms in clinical trials of esketamine in depression: a systematic review

Published online by Cambridge University Press:  26 April 2023

Tanguy Taillefer de Laportalière Open the ORCID record for Tanguy Taillefer de Laportalière [Opens in a new window] ,
Adeline Jullien ,
Antoine Yrondi ,
Philippe Cestac  and
François Montastruc Open the ORCID record for François Montastruc [Opens in a new window]
Tanguy Taillefer de Laportalière*
Affiliation:
Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance and Pharmacoepidemiology, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France
Adeline Jullien
Affiliation:
Department of Pharmacy, Toulouse University Hospital (CHU), Toulouse, France
Antoine Yrondi
Affiliation:
Department of Medical Psychiatry, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France Treatment Resistant Depression Expert Center, FondaMental, Toulouse, France ToNIC Toulouse NeuroImaging Center, University Paul Sabatier Toulouse, INSERM, Toulouse, France
Philippe Cestac
Affiliation:
Department of Pharmacy, Toulouse University Hospital (CHU), Toulouse, France
François Montastruc
Affiliation:
Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance and Pharmacoepidemiology, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France Department of Medical Psychiatry, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France Centre d'Investigation Clinique 1436, Team PEPSS ‘Pharmacologie En Population cohorteS et biobanqueS’, Toulouse University Hospital, France
*
Corresponding author: Tanguy Taillefer de Laportalière, E-mail: [email protected]
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Abstract

While previous systematic reviews of trials evaluating conventional antidepressants highlighted inadequacies and inconsistencies in adverse event (AE) reporting, no evaluation is available on esketamine in resistant depression. The objective of this review was to assess quality of reporting AEs in all published clinical trials studying esketamine. It also aimed to compare the proportions of AEs reported in journal articles to those recorded in the ClinicalTrial.gov Registers. Clinical trials evaluating the efficacy and safety of esketamine in depression were searched using Medline and ClinicalTrials.gov. The quality of reporting harms was assessed using a 21-item checklist from the CONSORT Extension of Harms (1 point by item). The total quality score was graded into four categories: high (17–21), moderate (12–16), low (7–11) and very low (0–6). Ten clinical trials were included in the analysis. Nine trials were classified as ‘low quality’ with regard to safety, one trial was classified as ‘moderate quality’. Compared to AEs recorded in ClinicalTrials.gov, we found that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles. Among them, the majority were psychiatric events but also cardiovascular events and 94% concerned patients from esketamine groups. Quality of AEs reporting in published clinical trials of esketamine was poor and harms were reported less frequently in journal publications than in ClinicalTrial.gov Registers. The study suggests that an assessment of the benefits/risks balance of esketamine based on the results reported in trial publications is flawed due to the poor accuracy and completeness of harm data.

Keywords

Adverse eventesketaminequality of reportingtreatment-resistant depression
Type
Review Article
Information
Psychological Medicine , Volume 53 , Issue 10 , July 2023 , pp. 4305 - 4315
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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