Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
Ammendolia, I., Calapai, F., Calapai, G., Cardia, L., Curro, M., Esposito, E., Mannucci, C., Midiri, P., Mondello, C.
This pharmacovigilance analysis (n=751) examines suspected adverse reactions (SARs) to esketamine nasal spray (Spravato) reported in the EudraVigilance database across European countries. The study identifies increased blood pressure (15.4%) and dissociation (15%) as the most common SARs, with data suggesting a potentially higher risk of suicidality with esketamine compared to fluoxetine and venlafaxine, prompting recommendations for careful monitoring of patients with a history of suicidal ideation.
Abstract
Background/Objective: Major depressive disorder (MDD) is a common mental disorder, with a significant portion of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination with other antidepressants for adults with TRD. Signals of suspected adverse reactions (SARs) to esketamine from the EudraVigilance database in European countries were analyzed for a more defined safety profile of this drug in the real world. Methods: SARs to esketamine reported in the data system EudraVigilance were analyzed, and disproportionality analysis for adverse reactions indicating suicidality for esketamine, in comparison to the antidepressants fluoxetine and venlafaxine, was performed. Results: Increases in blood pressure (15.4%) and dissociation (15.0%) were the most frequently reported SARs. The sex distribution indicates the prevalence of women, except for increased blood pressure and completed suicide, which were signaled in men, while adults (18-64 years) and elders (65-85 years) were the ages with the largest number of reported adverse reactions to esketamine. The results indicate the existence of a potential increase in the risk of suicide in depressed patients taking esketamine when compared with fluoxetine and venlafaxine. Conclusions: Apart from carefulness due to the known limitations of pharmacovigilance research conducted by using data systems of spontaneous signals for SARs, the analysis of data points toward the need for greater attention being paid to the potential risk of suicide following the prescription of esketamine in depressed subjects. In this regard, as regulatory agencies also recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to beginning treatment should receive more careful monitoring during treatment.