Review information published in the Cochrane Database of Systematic Reviews recommend that ketamine and esketamine are successful selections for the brief-term remedy of significant depressive disorder. However, the certainty of proof varied extensively across the trials reviewed.
Investigators searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and PsycINFO databases from inception via July 2020 for randomized clinical trials of glutamate receptor modulators for the remedy of depression. Eligible trials enrolled adults and compared glutamate receptor modulators with placebo, other active psychotropic drugs, or electroconvulsive therapy (ECT).Three critique authors independently identified research, assessed trial high-quality, and extracted information. The key outcomes have been remedy response price and adverse events. Risk of bias was assessed making use of the Cochrane tool certainty of proof was evaluated making use of Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria.
The critique incorporated 64 research with a pooled cohort of 5299 patients. The majority of research (75%) have been placebo controlled. Most research restricted enrollment to patients with moderate to serious depression or remedy-resistant depression. Studied drugs incorporated ketamine (n=31 trials), esketamine (9), memantine (5), lanicemine (4), D-cycloserine (2), Org26576 (2), riluzole (2), atomoxetine (1), basimglurant (1), citicoline (1), CP-101,606 (1), decoglurant (1), MK-0657 (1), N-acetylcysteine (1), rapastinel (1), and sarcosine (1). Ketamine was administered as a single dose in most connected trials, when esketamine had an established dosing regimen, such as twice a week for 4 weeks. Ketamine was most normally administered intravenously, when esketamine was offered intranasally.
Per the benefits of 7 research with a combined cohort of 185 patients, ketamine was connected with elevated response and remission prices at 24 hours following administration vs placebo (odds ratio [OR], 3.94 95% CI, 1.54-10.10). Ketamine was also connected with decreased depression rating scale scores in 8 research. However, the proof for each of these associations was of low certainty. Study attrition prices have been not distinctive among placebo and ketamine groups. Two trials compared ketamine with midazolam for the remedy of depression. Compared with midazolam, ketamine had an enhanced 24-hour remission price (OR, 2.21 95% CI, .67-7.21), despite the fact that the distinction was not statistically considerable.
Esketamine was similarly connected with elevated 24-hour remission prices compared with placebo, as determined by the benefits of 5 research with 894 participants (OR, 2.74 95% CI, 1.71-4.40). The proof for this association was of moderate certainty. According to further moderate-certainty proof from 4 research, esketamine was connected with decreased depression rating scale scores at 24 hours compared with placebo (typical imply distinction [SMD]: -.31 95% CI, -.45 to -.17). Trial drop-out was not elevated amongst esketamine recipients compared with the placebo arm.
Very tiny information have been out there for the efficacy of the remaining glutamate receptor modulators. Risk of bias was low or unclear across most research, when information certainty ranged from low to moderate. Overall, the proof points to the probable efficacy of ketamine and esketamine more than placebo at 24 hours following administration. However, the extended-term effects of these therapies stay unclear. “Long term non-inferiority [randomized controlled trials] comparing repeated ketamine and esketamine, and rigorous real-world monitoring are needed to establish comprehensive data on safety and efficacy,” authors concluded.
Disclosure: Two study authors declared affiliations with biotech, pharmaceutical, and/or device corporations. Please see the original reference for a complete list of authors’ disclosures.
Dean RL, Hurducas C, Hawton K, et al. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 20219(9):CD011612. doi:10.1002/14651858