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

• Published in: Psychopharmacology 2018-04, Vol.235 (4), p.1107-1119
• Main Authors: Morrison, Randall L., Fedgchin, Maggie, Singh, Jaskaran, Van Gerven, Joop, Zuiker, Rob, Lim, Kyoung Soo, van der Ark, Peter, Wajs, Ewa, Xi, Liwen, Zannikos, Peter, Drevets, Wayne C.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Adult; Antidepressants; Bioavailability; Biomedical and Life Sciences; Biomedicine; Blood pressure; Cognition - drug effects; Cognition - physiology; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive tasks; Cross-Over Studies; Dizziness - chemically induced; Double-Blind Method; Double-blind studies; Drug dosages; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - chemistry; Fatigue; Fatigue - chemically induced; Female; Follow-Up Studies; Healthy Volunteers; Humans; Ketamine; Ketamine - administration & dosage; Ketamine - adverse effects; Ketamine - analogs & derivatives; Male; Maze learning; Maze Learning - drug effects; Maze Learning - physiology; Memory; Mental depression; Middle Aged; Nausea; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Psychopharmacology; R&D; Randomization; Research & development; Sleep and wakefulness; Sleepiness; Treatment Outcome; Young Adult
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-4828-5

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