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Review
. 2023 Dec 13;15(12):2773.
doi: 10.3390/pharmaceutics15122773.

The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review

Ludivine Boudieu  1 , Myriam Mennetrier  1 , Pierre-Michel Llorca  1 , Ludovic Samalin  1
Affiliations
Review

The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review

Ludivine Boudieu et al. Pharmaceutics. .

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.

Keywords: esketamine; intranasal formulation; ketamine; major depressive disorder; treatment-resistant depression.

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Conflict of interest statement

Ludovic Samalin has received personal fees and/or non-financial support from Janssen-Cilag, Lundbeck, Otsuka, Rovi, and Sanofi-Aventis. Pierre-Michel Llorca has received personal fees and/or non-financial support from Eisai, Ethypharm, Janssen, Lundbeck, MSD, Neuraxpharm, Novartis, Otsuka, Roche, Rovi, and Sanofi. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart.
See this image and copyright information in PMC

References

    1. Charlson F., van Ommeren M., Flaxman A., Cornett J., Whiteford H., Saxena S. New WHO Prevalence Estimates of Mental Disorders in Conflict Settings: A Systematic Review and Meta-Analysis. Lancet. 2019;394:240–248. doi: 10.1016/S0140-6736(19)30934-1. - DOI - PMC - PubMed
    1. Hasin D.S., Sarvet A.L., Meyers J.L., Saha T.D., Ruan W.J., Stohl M., Grant B.F. Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States. JAMA Psychiatry. 2018;75:336–346. doi: 10.1001/jamapsychiatry.2017.4602. - DOI - PMC - PubMed
    1. Holma K.M., Melartin T.K., Haukka J., Holma I.A.K., Sokero T.P., Isometsä E.T. Incidence and Predictors of Suicide Attempts in DSM-IV Major Depressive Disorder: A Five-Year Prospective Study. Am. J. Psychiatry. 2010;167:801–808. doi: 10.1176/appi.ajp.2010.09050627. - DOI - PubMed
    1. Rush A.J., Thase M.E., Dubé S. Research Issues in the Study of Difficult-to-Treat Depression. Biol. Psychiatry. 2003;53:743–753. doi: 10.1016/S0006-3223(03)00088-X. - DOI - PubMed
    1. Rush A.J., Trivedi M.H., Wisniewski S.R., Nierenberg A.A., Stewart J.W., Warden D., Niederehe G., Thase M.E., Lavori P.W., Lebowitz B.D., et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. Am. J. Psychiatry. 2006;163:1905–1917. doi: 10.1176/ajp.2006.163.11.1905. - DOI - PubMed

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