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

This systematic review (s=10 trials) evaluates the quality of adverse event (AE) reporting in published clinical trials studying esketamine for resistant depression. It reveals that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles compared to ClinicalTrials.gov, with the majority being psychiatric and cardiovascular events and 94% concerning patients from esketamine groups. The study concludes that the quality of AE reporting in esketamine trials is poor, making the assessment of benefits/risks based on trial publications flawed due to the inaccuracy and incompleteness of harm data.

Abstract of Reporting of harms in clinical trials of esketamine in depression

“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.”

Authors: Tanguy T. de Laportalière, Adeline Jullien, Antoine Yrondi, Philippe Cestac & François Montastruc

Summary of Reporting of harms in clinical trials of esketamine in depression