The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review
Ludivine Boudieu, Myriam Mennetrier, Pierre-Michel Llorca, Ludovic Samalin
Pharmaceutics December 22, 2023 DOI: 10.3390/pharmaceutics15122773 via DOAJ
Summary
AI-generated from the abstractIntranasal ketamine and esketamine offer a rapid onset of antidepressant effects within hours for people with major depressive disorder, particularly those with treatment-resistant depression or active suicidal thoughts. A systematic review following PRISMA guidelines found stronger evidence of efficacy for intranasal esketamine than for intranasal ketamine. The safety profile of intranasal esketamine appears acceptable, though further studies are needed; a more accurate delivery device is required for ketamine. These glutamatergic agents bypass the blood–brain barrier, potentially reducing side effects compared with intravenous administration.
Study at a glance
| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Patients with major depressive disorder, including those with treatment-resistant depression or active suicidal ideation |
| Topics | Depression Esketamine Ketamine |
| Keywords | Intranasal formulation |
| Citations | 22 |
| Key finding | Intranasal esketamine has stronger evidence of efficacy than intranasal ketamine for major depressive disorder, with both providing rapid antidepressant action within hours. |
Abstract
Ketamine and its enantiomers represent an innovative glutamatergic agent as a treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation and behavior. Intranasal (IN) formulations could allow for quick onset of action on depressive symptoms as well as a reduction in side effects by bypassing the blood–brain barrier compared with administration via the intravenous route. The aim of this review was to provide an up-to-date analysis of the data on the efficacy and safety of IN ketamine and IN esketamine for the treatment of MDD. A systematic review following PRISMA guidelines was conducted. Databases (PubMed, Embase, MEDLINE, PsycINFO, and Google Scholar) were searched to capture articles about IN ketamine or IN esketamine for MDD. This systematic review highlighted the interest in IN routes of ketamine and esketamine for MDD patients with TRD or active suicidal ideation. They provide a rapid onset of antidepressant action within the first hours after administration. Nevertheless, the evidence of efficacy is stronger for IN esketamine than for IN ketamine in MDD patients. The safety profile appears to be acceptable for IN esketamine but requires further studies, and a more accurate IN delivery device is required for ketamine.