Safety Profile and Suicidality Associated with Use of Esketamine in the Treatment of Major Depressive Disorder

Background/ Objective: Major depressive disorder (MDD) is a common mental disorder, with a significant part 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 sui-cidality for esketamine, in comparison to the antidepressants fluoxetine and ven-lafaxine, was performed. Results: “Blood pressure increased” (15.4%) and “Dissocia-tion” (15.0%), are the more frequently reported SARs. Sex distribution indicates prevalence of women, except for “Blood pressure increased” and “Completed suicide”, more signaled for men, while adults (18-64 years) and elders (65-85 years) are the ages with the largest number of reported adverse reactions to esketamine. Results show a significant increase of risk of suicide for esketamine, when compared with fluoxetine and venlafaxine. Conclusions: Apart of carefulness due to the known limitations of pharmacovigilance research conducted by using datasystem of spontaneous signals for SARs, analysis of data on points towards the need for greater attention for risk suicide following prescription of esketamine in depressed subjects. In this regard, as well as regulatory agencies recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to begin treatment, should receive a more careful monitoring during treatment.