Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study

@article{Schoedel2016AssessmentOT,
  title={Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study},
  author={Kerri A. Schoedel and Hong Sun and Edward Sellers and Janice Faulknor and N. Levy-Cooperman and Xiaodong Li and William P. Kennedy and Jang-Ho Cha and Nicole Lewis and Wen Liu and Phung Bondiskey and Jacqueline B McCrea and Deborah L. Panebianco and Matthew D. Troyer and John A. Wagner},
  journal={Journal of Clinical Psychopharmacology},
  year={2016},
  volume={36},
  pages={314–323}
}
Abstract Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2–7.5 × maximum dose), zolpidem (15 and 30 mg: 1.5–3 × maximum dose), and placebo were administered, with a 10… 

Abuse potential assessment of the new dual orexin receptor antagonist daridorexant in recreational sedative drug users as compared to suvorexant and zolpidem.

In this large, valid human abuse potential study, daridorexant showed dose-related drug-liking among recreational sedative drug users with lower effects at the highest phase-3 dose, and similar effects at higher doses compared to supratherapeutic doses of suvoreXant and zolpidem.

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

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.

Acute Cognitive Effects of the Dual Orexin Receptor Antagonist Lemborexant Compared With Suvorexant and Zolpidem in Recreational Sedative Users

All active doses of LEM, ZOL, and SUV generally increased reaction time and reduced divided attention capabilities versus PBO, however, at therapeutic/supratherapeutic doses, LEM led to significantly less cognitive impairment than supratherapeutic dose of ZOL in some measures.

Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant

Nonclinical evaluation of abuse liability of the dual orexin receptor antagonist lemborexant.

A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity

Investigation of the effect of seltorexant on sleep efficiency after single and multiple dose administration in subjects with insomnia disorder without psychiatric comorbidity resulted in a prolonged total sleep time, shorter latency to persistent sleep and wake after sleep onset.

Novel class of medications, orexin receptor antagonists, in the treatment of insomnia – critical appraisal of suvorexant

Suvorexant is not likely to replace benzodiazepines or nonbenzodiazepine receptor antagonists as a first-line sleep agent but does represent a novel option for the treatment of patients with chronic insomnia.

The selective orexin-2 receptor antagonist seltorexant improves sleep: An exploratory double-blind, placebo controlled, crossover study in antidepressant-treated major depressive disorder patients with persistent insomnia

Seltorexant showed a statistically significant, dose-dependent decrease in latency to persistent sleep, and increase in total sleep time and sleep efficiency combined with a tendency toward subjectively improved mood.

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper

Suvorexant reduced sleep disturbance during opioid withdrawal and may improve opioid use disorder treatment outcomes, and targeting the orexin signaling might reduce the negative effects of opioid withdrawal on sleep quality.

References

SHOWING 1-10 OF 49 REFERENCES

Subjective and Objective Effects of the Novel Triple Reuptake Inhibitor Tesofensine in Recreational Stimulant Users

The study results show that the effects of D‐amphetamine were significantly greater than those of placebo on all primary and secondary subjective measures and tesofensine is therefore unlikely to be recreationally abused.

Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine

Do Formulation Differences Alter Abuse Liability of Methylphenidate?: A Placebo-Controlled, Randomized, Double-Blind, Crossover Study in Recreational Drug Users

The results suggest that OROS methylphenidate, with its characteristic slow ascending plasma concentration profile, may have lower abuse potential, reflected by lower subjective responses during early hours as compared with the IR formulation with its rapid drug delivery and accompanying greater subjective effects.

Orexin receptor antagonism: an ascending multiple-dose study with almorexant

Almorexant at 400 and 1000 mg administered in the morning reduced vigilance, alertness, visuomotor coordination, and motor coordination assessed in a psychometric test battery, and polysomnography recordings following evening administration showed a trend towards short latency to sleep stages 3 and 4, and shorter latency to rapid-eye-movement sleep at higher doses when compared to placebo.

Modest abuse-related subjective effects of zolpidem in drug-naive volunteers

Although individuals without a drug abuse history are not inclined to choose zolpidem when presented with an alternative reinforcer such as money, it may possess moderate abuse potential that limits its clinical utility.

Promotion of Sleep by Suvorexant—A Novel Dual Orexin Receptor Antagonist

Dosed orally Suvorexant significantly and dose-dependently reduced locomotor activity and promoted sleep in rats, dogs, and rhesus monkeys, highlighting a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia.

Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group.

Zaleplon appears to provide a favorable safety profile, as indicated by the absence of rebound insomnia and withdrawal symptoms once treatment was discontinued, and was effective in the treatment of insomnia in outpatients with DSM-III-R insomnia.

Guidelines for the Rational Use of Benzodiazepines

Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia.

Guidelines for the rational use of benzodiazepines. When and what to use.

Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia, and occasionally in acute psychoses.