Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study
Randall L. Morrison, Maggie Fedgchin, Jaskaran Singh, Joop van Gerven, Rob G J A Zuiker, Kyoung Soo Lim, Peter van der Ark, Ewa Wajs, Liwen Xi, Peter Zannikos, Wayne C. Drevets
Psychopharmacology February 1, 2018 DOI: 10.1007/s00213-018-4828-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Healthy participants |
| Intervention | Intranasal esketamine |
| Duration | 6 hours postdose |
| Topics | Esketamine |
| Keywords | Placebo Anesthesia Crossover study Adverse effect Nasal administration Pharmacology |
| Citations | 72 |
| Registration | NCT02094378 |
| Key findings | Intranasal esketamine caused significant but transient cognitive impairment and increased mental effort and sleepiness at 40 minutes postdose, with effects returning to placebo-comparable levels by 2 hours. |
Abstract
Background: The effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study.
Methods: 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.