Safety concerns on the abuse potential of esketamine : Multidimensional analysis of a new anti-depressive drug on the market

Safety concerns on the abuse potential of esketamine : Multidimensional analysis of a new anti-depressive drug on the market

Auteurs : J. Bau­dot, T. Soei­ro, M. Tam­bon, N. Navar­ro, G. Vey­rac, S. Mezaache, J. Micallef

Réfé­rence : Fun­da­men­tal & Cli­ni­cal Phar­ma­co­lo­gy (Ear­ly view)

Abstract

Pro­minent fea­tures of eske­ta­mine (e.g., simi­lar mecha­nism of action as keta­mine and tar­get popu­la­tion) require to be vigi­lant regar­ding its benefits/risks balance and its risks of abuse in real-life set­tings. The aim of this stu­dy was to review all avai­lable phar­ma­co­lo­gi­cal and cli­ni­cal data to assess the abuse poten­tial of eske­ta­mine short­ly after its mar­ke­ting. This mul­ti­di­men­sio­nal stu­dy is a quan­ti­ta­tive and qua­li­ta­tive ana­ly­sis of com­ple­men­ta­ry data sources, ran­ging from preau­tho­ri­za­tion data (i.e., fun­da­men­tal phar­ma­co­lo­gy and cli­ni­cal trials) to real-life set­tings data (i.e., phar­ma­co­vi­gi­lance data­bases and web forums). Accor­ding to eske­ta­mine phar­ma­co­lo­gy, its psy­choac­tive effects play a role both in its the­ra­peu­tic effect and its abuse poten­tial. Only one out of the three short-term effi­ca­cy trials found a signi­fi­cant dif­fe­rence bet­ween eske­ta­mine and pla­ce­bo in treat­ment-resis­tant depres­sion. Beside adverse events that may be sought for abuse pur­pose (e.g., dis­so­cia­tion, seda­tion, eupho­ric mood, hal­lu­ci­na­tion, fee­ling drunk, and derea­li­za­tion), cli­ni­cal signs rela­ted to sub­stance use disor­der (e.g., tole­rance, with­dra­wal syn­drome, and drug depen­dence) and misuse (e.g., off-label use) were also iden­ti­fied in phar­ma­co­vi­gi­lance data­bases. Ana­ly­sis of phar­ma­co­vi­gi­lance nar­ra­tives and web forums sho­wed that eske­ta­mine psy­choac­tive effects are appre­cia­ted by some patients, while they are bad­ly expe­rien­ced by others. Strict com­pliance with the mar­ket autho­ri­za­tion, close moni­to­ring of patients by psy­chia­trists, and sur­veillance of any signs of misuse, abuse, or depen­dence must be part of any treat­ment course.