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Psychopharmacology (Berl). 2018 Apr;235(4):1107-1119. doi: 10.1007/s00213-018-4828-5. Epub 2018 Feb 1.

Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study.

Author information

1
Neuroscience Integrative Solutions, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA. rmorris5@its.jnj.com.
2
Janssen Research & Development, LLC, Titusville, NJ, USA. rmorris5@its.jnj.com.
3
Janssen Research & Development, LLC, Titusville, NJ, USA.
4
Centre for Human Drug Research, Leiden, The Netherlands.
5
CHA University School of Medicine and CHA Budang Medical Center, Seongnam, South Korea.
6
Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.

Abstract

BACKGROUND:

The effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study.

METHODS:

Twenty-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.

RESULTS:

Esketamine 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.

CONCLUSIONS:

Esketamine 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 REGISTRATION:

ClinicalTrials.gov identifier: NCT02094378.

KEYWORDS:

Cognitive functioning; Cogstate® computerized test battery; Intranasal esketamine; Treatment-resistant depression

PMID:
29392371
PMCID:
PMC5869899
DOI:
10.1007/s00213-018-4828-5
[Indexed for MEDLINE]
Free PMC Article

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