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) via OpenAlex
Summary
AI-generated from the abstractIntranasal esketamine temporarily impairs cognitive performance and increases mental effort and sleepiness in healthy participants. At 40 minutes after dosing, performance on five cognitive tests (Detection, Identification, One-Card Learning, One Back, and Groton Maze Learning) was significantly worse compared with placebo. These effects resolved by 2 hours postdose, with no differences between esketamine and placebo at 2, 4, or 6 hours. Participants reported greater mental effort at 40 minutes and increased sleepiness at 40 minutes and 2 hours, which also returned to placebo levels later. Common mild adverse events included dizziness, nausea, attention disturbance, and fatigue.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Healthy participants |
| Intervention | Intranasal esketamine |
| Duration | 6 hours postdose |
| Keywords | Placebo Anesthesia Crossover study Adverse effect Psychology |
| Citations | 72 |
| Registration | NCT02094378 |
| Key finding | 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.