| アブストラクト | INTRODUCTION: Ketamine and esketamine have been proven to be effective in treating adults with treatment resistant depression (TRD). Preliminary evidence indicates that, when combined with behavioral and psychological interventions, both agents may offer benefits for individuals with substance use disorder (SUD) and alcohol use disorder (AUD). Notwithstanding, concerns have been raised as to whether either or both agents are associated with abuse and/or gateway activity. METHODS: Herein, we evaluate disproportionate reporting expressed as reporting odds ratios (ROR) for esketamine and ketamine. The outcomes of interest include alcohol problem, alcoholism, alcohol abuse, substance dependence, SUD, substance abuse, drug dependence, drug use disorder and drug abuse as codified by the Medical Dictionary for Regulatory Activities (MedDRA) within the FAERS. The IC025 values were significant for ketamine in cases of alcohol abuse (0.28), substance dependence (1.88), substance use disorder (0.996), substance abuse (0.61), drug dependence (0.56), drug use disorder (1.17) and drug abuse (1.22). Additionally, oxycontin showed significant IC025 values for substance dependence (0.067), substance use disorder (0.094), substance abuse (0.035), and drug dependence (0.27). RESULTS: We observed significant increases in the reporting odds ratios (RORs) for ketamine with respect to various outcomes: alcohol abuse (ROR 2.84, 95 % CI 1.53-5.28; p = 0.0010), substance dependence (ROR 18.72, 95 % CI 8.49-41.30; p </= 0.0001), SUD (ROR 11.40, 95 % CI 4.24-30.65; p </= 0.0001), substance abuse (ROR 2.29, 95 % CI 1.73-3.04; p </= 0.0001), drug dependence (ROR 1.99, 95 % CI 1.64-2.42; p </= 0.0001), drug use disorder (ROR 4.50, 2.94-6.88; p </= 0.0001) and drug abuse (ROR 3.72, 3.36-4.12; p </= 0.0001). For esketamine, we observed that the ROR was significantly reduced for substance abuse (ROR 0.37, 95 % CI 0.22-0.63; p = 0.0003), drug dependence (ROR 0.13, 95 % CI 0.076-0.23; p </= 0.0001) and drug abuse (ROR 0.048, 95 % CI 0.030-0.078; p </= 0.0001). To our knowledge, this is the first report of spontaneous adverse events related to these outcomes of interest in the FAERS. CONCLUSION: Mixed RORs were observed across aspects of SUD and AUD for both ketamine and esketamine. Due to limitations in the FAERS, establishing causal links between new onset alcohol and substance misuse with either agent remains inconclusive. Possible beneficial effects on measures of SUD and AUD were observed. It is currently unclear, but possible, whether both agents have differential ameliorative effects across dimensions of SUD and AUD, which is a focus of ongoing research. |
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| ジャーナル名 | Journal of affective disorders |
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| 投稿日 | 2024/5/26 |
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| 投稿者 | Kwan, Angela T H; Rosenblat, Joshua D; Mansur, Rodrigo B; Teopiz, Kayla M; McIntyre, Roger S |
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| 組織名 | Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Brain and;Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address:;angela.kwan@mail.utoronto.ca.;Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Mood;Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University;Health Network, Toronto, Ontario, Canada. Electronic address:;joshua.rosenblat@uhn.ca.;rodrigo.mansur@uhn.ca.;Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic;address: kayla.teopiz@mail.utoronto.ca.;Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Department of;Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of;Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada;;Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University;roger.mcintyre@bcdf.org. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38795777/ |
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