Long-term safety and efficacy of daridorexant in patients with insomnia disorder

Kunz, Dieter; Beneŝ, Heike; García-Borreguero, D.; Dauvilliers, Yves; Plazzi, G.; Sassi-Sayadi, Mouna; Coloma, Preciosa; Kinter, Dalma Seboek; Thein, S.

doi:10.1016/j.sleep.2022.05.356

Cited by 3 publications

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“…Study treatment dose adjustments were not permitted. The treatment period was followed by a 7-day, singleblind, placebo run-out period and then either a 23-day safety follow-up or enrolment into a 40-week placebo-controlled extension study (NCT03679884; results reported elsewhere [38]). The study was conducted in ten countries (Australia, Canada, Denmark, Germany, Italy, Poland, Serbia, Spain, Switzerland and the USA) at 75 sites between May 2018 and May 2020, in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Guideline for Good Clinical Practice and local regulations.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

et al. 2022

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Background and ObjectiveThe dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults'). Methods Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, doubleblind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness. Results At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour. Conclusions In older patients with insomnia, as in younger patients, the effi...

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Section: Methodsmentioning

confidence: 99%

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

et al. 2022

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Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia

Watson

Benca

Krystal

et al. 2023

JCM

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Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1–2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.

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Use of Daridorexant among Patients with Chronic Insomnia: A Retrospective Observational Analysis

Williams

Rodriguez-Cué²

2023

JCM

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Insomnia is the most prevalent sleep disorder, affecting millions worldwide and taking a heavy toll on patient health with significant social and economic impact. Even though there are multiple different types of insomnia medications and behavioral therapies, there are still many individuals for whom treatment remains ineffective. The objective of this retrospective study was to analyze the effectiveness of daridorexant in a cohort of chronic insomnia patients largely transitioned from GABA-A positive allosteric modulators (benzodiazepines, zolpidem or eszopiclone) or other frequently prescribed insomnia medications (including trazodone, atypical antipsychotics or tricyclic antidepressants). A total of 86 patients were treated in the course of ordinary practice and the primary analytic endpoint was the change in Insomnia Severity Index (ISI) score following ≥ 30 nights of treatment with daridorexant. Results from 80 of the 86 patients with full data (65% female, mean age 53.5 years, 18.8% with comorbid obstructive sleep apnea, 91.3% transitioned from a different medication) showed a mean improvement in ISI score of 7.0 ± 0.54 points (SEM) (p < 0.0001) from 18.0 to 11.0. Overall, 78% of the cohort demonstrated a clinically meaningful improvement as defined by at least a six-point drop in ISI. Total sleep time increased by 54 ± 1.0 min (SEM) (p < 0.0001) from 6.0 h to 6.9 h. Mean sleep latency decreased by 23.9 ± 2.4 min (SEM) (p < 0.0001) from 58.8 min to 34.9 min. Wake after sleep onset decreased by 31.6 ± 3.2 min (SEM) (p < 0.001) from 42.8 min to 11.3 min. Sleep efficiency improved by 10.5 ± 1.1% (SEM) (p < 0.0001) from 79.3% to 89.8%. No significant adverse events were noted during the study duration. Keeping in mind this study’s limitations, these data suggest that for insomnia patients with an incomplete response to current therapy, switching to daridorexant is safe and may be an effective alternative treatment.

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Long-term safety and efficacy of daridorexant in patients with insomnia disorder

Cited by 3 publications

References 0 publications

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia

Use of Daridorexant among Patients with Chronic Insomnia: A Retrospective Observational Analysis

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