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Esketamine is the mirror image molecule of ketamine. The two molecules are very similar biologically, but esketamine is reported to produce fewer psychomimetic side effects like delirium or hallucinations.
Ella Daly, M.D., of Janssen Research and Development and colleagues recruited 67 adults with treatment-resistant depression; treatment resistance was defined as having a history of inadequate response to two or more antidepressants. The patients were randomly divided so that half received placebo while the other half received 28 mg, 56 mg, or 84 mg of esketamine twice weekly for two weeks. All participants continued the antidepressants they were receiving at study entry during the trial.
The researchers found that all three esketamine doses produced significantly greater reductions in the participants’ Montgomery-Asberg Depression Rating Scale scores from baseline after one week. The improvements escalated with dose, with 4.2, 6.3, and 9.0-point improvements for the 28 mg, 56 mg, and 84 mg doses, respectively.
After 15 days, all participants were invited to enroll in a 60-day open-label period, during which they received esketamine twice weekly for two weeks, weekly for three weeks, and then every two weeks thereafter. The improvements in depressive symptoms were maintained during the open-label period despite the reduced dosing frequency, and for up to two months after the discontinuation of esketamine.
“In general, the esketamine doses used in this study appeared to be safe, with no new or unexpected safety concerns observed,” the authors wrote. “Overall, transient increases in blood pressure after the dose, particularly increases in systolic blood pressure, support an increase in cardiac output as the underlying mechanism, consistent with previous reports of ketamine.”
To read more about this topic, see the Psychiatric News article “Ketamine Is a Potent Antidepressant, but How Does It Work?”
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