Summary

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• This summary is based on the review of 27 systematic review(s)/meta-analysis(es). ^[1-27]
• Esketamine demonstrated significantly higher remission rates (RR (relative risk) = 1.371, 95% CI (confidence interval): 1.194 to 1.574, p < 0.0001) and response rates (RR = 1.274, 95% CI: 1.108 to 1.465, p = 0.001) compared to placebo in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD), with more pronounced effectiveness at higher doses (84 mg) and flexible dosing regimens.
• In adolescents with MDD and suicidal ideation, esketamine reduced depressive symptoms and suicidal ideation, with favorable safety and tolerability profiles reported.
• Compared to racemic ketamine, esketamine showed significant immediate antidepressant effects, though racemic ketamine exhibited greater effect sizes for depression severity, response, and remission rates, and more sustained effects during repeated dosing.
• Esketamine combined with standard of care (SOC) improved health-related quality of life and treatment satisfaction in patients with MDD and active suicidal ideation, with anti-suicidal ideation effects observed within 4-6 hours and lasting up to 24 hours.
• Adverse events commonly associated with esketamine included nausea, dizziness, dissociation, vertigo, hypoesthesia, sedation, and paresthesia; serious adverse events were less frequently reported in journal articles compared to ClinicalTrials.gov records.
• Esketamine was linked to higher rates of discontinuation due to intolerability and transient increases in blood pressure and heart rate, which were generally mild and manageable. Long-term safety concerns included the risk of abuse and undefined long-term side effects.
• Racemic ketamine and esketamine both caused transient dissociative symptoms and common adverse events without persistent psychoses or affective switches, but esketamine had fewer reported adverse events in clinical trials compared to racemic ketamine.
• Esketamine showed stable efficacy in relapse prevention during long-term treatment in adults with TRD, with higher doses yielding more pronounced effects.