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Abuse Potential of Lemborexant, a Dual Orexin Receptor Antagonist, Compared With Zolpidem and Suvorexant in Recreational Sedative Users - PubMed

Randomized Controlled Trial

. 2022 Jul-Aug;42(4):365-373.

doi: 10.1097/JCP.0000000000001561. Epub 2022 Jun 24.

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Randomized Controlled Trial

Abuse Potential of Lemborexant, a Dual Orexin Receptor Antagonist, Compared With Zolpidem and Suvorexant in Recreational Sedative Users

Ishani Landry et al. J Clin Psychopharmacol. 2022 Jul-Aug.

Abstract

Background: Lemborexant (LEM) is a dual orexin receptor antagonist approved for the treatment of insomnia in adults in multiple countries including the the United States, Japan, Canada, Australia and several Asian countries.

Procedures: This was a randomized, single-dose, single-center, double-blind, active-control, 6-way crossover study to evaluate LEM abuse potential. The study assessed oral doses of LEM 10 mg (LEM10), 20 mg (LEM20), and 30 mg (LEM30) compared with placebo (PBO), zolpidem (ZOL) immediate release 30 mg, and suvorexant (SUV) 40 mg. Subjects were healthy, nondependent, recreational sedative users able to discriminate/like the effects of both SUV and ZOL from PBO during a qualification phase.

Results: Abuse potential endpoints were analyzed in qualified subjects who received and completed all treatments (n = 32). On the "at this moment" drug-liking visual analog scale (VAS), mean maximum (peak) effect (primary endpoint) values were 78.4, 80.5, and 83.6 for LEM10, LEM20, and LEM30, respectively, which were all significantly greater than PBO (57.8; all P > 0.05) but not different from SUV (76.1) or ZOL (78.3). Similarly, for secondary endpoints overall drug-liking VAS and take-drug-again VAS, mean maximum (peak) effect values for all LEM doses were significantly greater than PBO ( P > 0.05) but not different compared with ZOL or SUV.

Conclusions: For all doses, LEM demonstrated abuse potential versus PBO and appeared to have a similar abuse potential profile to ZOL and SUV in this study population. Lemborexant was well tolerated. Lemborexant has been placed in Schedule IV, the same drug schedule as ZOL and SUV.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

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Figures

FIGURE 1
FIGURE 1

Study design. PBO, placebo; ZOL, zolpidem 30 mg; SUV, suvorexant 40 mg; LEM10, lemborexant 10 mg; LEM20, lemborexant 20 mg; LEM30, lemborexant 30 mg.

FIGURE 2
FIGURE 2

Subject disposition. PBO, placebo; SUV, suvorexant 40 mg; ZOL, zolpidem 30 mg.

FIGURE 3
FIGURE 3

“At this moment” drug-liking VAS response to PBO, ZOL, SUV, and LEM. The primary endpoint was maximum (peak) effect (Emax). A, LSM (95% CI) differences in Emax between treatments. Validation margins of 11 and 15 points for the difference in means between the positive controls (ZOL and SUV) and PBO are indicated. B, Mean (SE) drug-liking VAS score over time for each treatment group. CI, confidence interval; Emax, maximum (peak) effect; LEM10, lemborexant 10 mg; LEM20, lemborexant 20 mg; LEM30, lemborexant 30 mg; LSM, least squares mean; PBO, placebo; SE, standard error; SUV, suvorexant 40 mg; VAS, visual analog scale; ZOL, zolpidem 30 mg.

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