• Randall L Morrison, Maggie Fedgchin, Jaskaran Singh, Joop Van Gerven, Rob Zuiker, Kyoung Soo Lim, Peter van der Ark, Ewa Wajs, Liwen Xi, Peter Zannikos, and Wayne C Drevets.
• Neuroscience Integrative Solutions, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA. rmorris5@its.jnj.com.
• Psychopharmacology (Berl.). 2018 Apr 1; 235 (4): 1107-1119.

BackgroundThe effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study.MethodsTwenty-four participants (19-49 years) were randomized to one of two treatment sequences in which either esketamine 84 mg or placebo was intranasally administered in a double-blind, two-period crossover design. Primary measures included five tests of Cogstate® computerized test battery assessed at 1 h predose and 40 min, 2, 4, and 6 h postdose. Secondary measures included the Mental Effort Scale, Karolinska Sleepiness Scale (KSS), and safety.ResultsEsketamine was associated with significant cognitive performance impairment at 40 min postdose for all five Cogstate® tests (Detection p = 0.0011, Identification p = 0.0006, One-Card Learning p = 0.0040, One Back p = 0.0017, and Groton Maze Learning Test p < 0.0001) versus placebo. In contrast, performance on these tests did not differ significantly between esketamine and placebo at 2, 4, or 6 h postdose. Secondary outcomes indicated a significant, transient increase from baseline under esketamine versus placebo at 40 min postdose on the Mental Effort Scale and at 40 min and 2 h postdose on KSS (p < 0.0001 for both); however, no significant difference was observed on these outcomes between esketamine and placebo at later timepoints. The most commonly reported adverse events were dizziness (67%), nausea (37.5%), disturbance in attention (29.2%), and fatigue (29.2%); the majority were considered mild in severity.ConclusionsEsketamine was associated with cognitive performance decline, and greater effort was required to complete the test battery versus placebo at 40 min postdose, which returned to placebo-comparable levels by 2 h postdose.Trial RegistrationClinicalTrials.gov identifier: NCT02094378.

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