Abstract：
BACKGROUND: 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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：氯胺酮和艾氯胺酮已被证明可有效治疗患有难治性抑郁症（TRD）的成人。初步证据表明,当与行为和心理干预相结合时，这两种药物都可以为患有物质使用障碍(SUD)和酒精使用障碍(AUD)的个体提供益处.尽管如此,有人担心其中一个或两个代理是否与滥用和/或网关活动有关。
方法：这里，我们评估了以报告比值比(ROR)表示的艾氯胺酮和氯胺酮的不成比例报告.感兴趣的结果包括酒精问题，酗酒,酗酒,物质依赖，SUD,药物滥用,药物依赖,由FAERS内的《监管活动医学词典》（MedDRA）编纂的药物使用障碍和药物滥用。在酒精滥用的情况下，氯胺酮的IC025值显着（0.28），物质依赖性（1.88），物质使用障碍（0.996），药物滥用（0.61），药物依赖（0.56），药物使用障碍（1.17）和药物滥用（1.22）。此外,奥施康定对物质依赖性显示出显著的IC025值(0.067)，物质使用障碍（0.094），药物滥用（0.035），和药物依赖性（0.27）。
结果：我们观察到氯胺酮在各种结果方面的报告优势比（ROR）显着增加：酒精滥用（ROR2.84，95％CI1.53-5.28；p=0.0010），物质依赖性（ROR18.72，95%CI8.49-41.30；p≤0.0001），SUD（ROR11.40，95%CI4.24-30.65；p≤0.0001），药物滥用（ROR2.29，95%CI1.73-3.04；p≤0.0001），药物依赖（ROR1.99，95%CI1.64-2.42；p≤0.0001），药物使用障碍(ROR4.50,2.94-6.88;p≤0.0001)和药物滥用(ROR3.72,3.36-4.12;p≤0.0001)。对于艾氯胺酮，我们观察到药物滥用的ROR显着降低（ROR0.37，95％CI0.22-0.63；p=0.0003），药物依赖(ROR0.13,95%CI0.076-0.23;p≤0.0001)和药物滥用(ROR0.048,95%CI0.030-0.078;p≤0.0001)。据我们所知,这是与FAERS关注的这些结局相关的自发性不良事件的首例报告.
结论：在SUD和AUD方面观察到氯胺酮和艾氯胺酮的混合ROR。由于FAERS的局限性，在新发的酒精和物质滥用与任何一种药物之间建立因果关系仍然没有定论。观察到对SUD和AUD测量的可能有益效果。目前还不清楚,但有可能,两种药物是否在SUD和AUD的维度上具有不同的改善作用，这是正在进行的研究的重点。
方法：这里，我们评估了以报告比值比(ROR)表示的艾氯胺酮和氯胺酮的不成比例报告.感兴趣的结果包括酒精问题，酗酒,酗酒,物质依赖，SUD,药物滥用,药物依赖,由FAERS内的《监管活动医学词典》（MedDRA）编纂的药物使用障碍和药物滥用。在酒精滥用的情况下，氯胺酮的IC025值显着（0.28），物质依赖性（1.88），物质使用障碍（0.996），药物滥用（0.61），药物依赖（0.56），药物使用障碍（1.17）和药物滥用（1.22）。此外,奥施康定对物质依赖性显示出显著的IC025值(0.067)，物质使用障碍（0.094），药物滥用（0.035），和药物依赖性（0.27）。
结果：我们观察到氯胺酮在各种结果方面的报告优势比（ROR）显着增加：酒精滥用（ROR2.84，95％CI1.53-5.28；p=0.0010），物质依赖性（ROR18.72，95%CI8.49-41.30；p≤0.0001），SUD（ROR11.40，95%CI4.24-30.65；p≤0.0001），药物滥用（ROR2.29，95%CI1.73-3.04；p≤0.0001），药物依赖（ROR1.99，95%CI1.64-2.42；p≤0.0001），药物使用障碍(ROR4.50,2.94-6.88;p≤0.0001)和药物滥用(ROR3.72,3.36-4.12;p≤0.0001)。对于艾氯胺酮，我们观察到药物滥用的ROR显着降低（ROR0.37，95％CI0.22-0.63；p=0.0003），药物依赖(ROR0.13,95%CI0.076-0.23;p≤0.0001)和药物滥用(ROR0.048,95%CI0.030-0.078;p≤0.0001)。据我们所知,这是与FAERS关注的这些结局相关的自发性不良事件的首例报告.
结论：在SUD和AUD方面观察到氯胺酮和艾氯胺酮的混合ROR。由于FAERS的局限性，在新发的酒精和物质滥用与任何一种药物之间建立因果关系仍然没有定论。观察到对SUD和AUD测量的可能有益效果。目前还不清楚,但有可能,两种药物是否在SUD和AUD的维度上具有不同的改善作用，这是正在进行的研究的重点。
