Daridorexant 25mg tablets

Background: Daridorexant is a novel dual orexin receptor antagonist that has shown efficacy as a treatment for insomnia in multiple randomized clinical trials. However, the efficacy and safety of daridorexant for treatment of insomnia disorder has not been characterized comprehensively in the literature. Therefore, we performed a meta-analysis of available studies. We performed a meta-analysis to systematically evaluate the efficacy and safety of daridorexant for treatment of insomnia disorder. Methods: MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials were systematically searched up to February 2022. Relative risk and standard mean difference were used to evaluate clinical outcomes. Results: We pooled 2271 patients from 4 randomized clinical trials, and evaluated efficacy endpoints. We found that 50 mg of daridorexant was superior to placebo for 4 efficacy outcomes including wake time after sleep onset, latency to persistent sleep, subjective total sleep time, and Insomnia Daytime Symptoms and Impacts Questionnaire domain score (P .05) in adverse events between daridorexant and placebo. Conclusions: Different dosages of daridorexant were tested for treatment of insomnia; however, 5 and 10 mg are not available because of issues of suboptimal effectiveness. Daridorexant showed better efficacy and safety for treatment of insomnia disorder at doses of 25 and 50 mg.

Abstract licence: CC BY-NC 4.0

BackgroundSleep disturbances, such as insomnia, are a group of prevalent and debilitating symptoms of Major Depressive Disorder (MDD). Dual Orexin Receptor Antagonists (DORAs) have emerged as potential treatments for insomnia and comorbid psychiatric conditions, such as MDD. We sought to comprehensively examine the efficacy, safety, and pharmacology of DORAs in the context of MDD and insomnia.MethodsWe performed a systematic review of primary research on daridorexant, lemborexant, and suvorexant retrieved from PubMed and OVID databases up to January 2025. Included studies were limited to randomized controlled trials and other studies investigating DORAs that examined the efficacy and safety of these agents on sleep architecture and depressive symptoms in individuals with MDD, Insomnia Disorder (ID), and healthy controls.ResultsA total of 19 studies were included in this review. DORAs demonstrated significant improvements in sleep onset latency, wake after sleep onset, and total sleep time, which were consistent across individuals with insomnia and comorbid MDD. The impact across DORAs on depressive symptoms was modest. The safety profiles were generally favourable, with most adverse events being mild to moderate.LimitationsThe studies reviewed were predominantly short-term and there was substantial variability in sample composition. Further research is needed to assess DORAs in larger, long-term clinical trials within the MDD population.ConclusionDORAs show potential in improving sleep parameters in individuals with MDD. While their effects on depressive symptoms in this review are modest, further research is needed to assess long-term efficacy, safety, and their impact on depressive symptoms, as well as to explore potential combination therapies.

Abstract licence: CC BY

Study objectivesChronic insomnia (CI) is common among older adults, and its management is particularly challenging due to changes in sleep architecture, multimorbidity, and increased vulnerability to adverse drug effects. Dual orexin receptor antagonists (DORAs) have emerged as a novel therapeutic class with promising efficacy and tolerability profiles. However, evidence specific to older adults remains limited. Here, we performed the first systematic review and meta-analysis specifically evaluating the efficacy and safety of DORAs in elderly patients with CI (PROSPERO CRD42024565687).MethodsRandomized controlled trials were identified from MEDLINE, Scopus, and ClinicalTrials.gov. Objective polysomnographic outcomes, including Latency to Persistent Sleep (LPS), Total Sleep Time (TST), and Wake After Sleep Onset (WASO), as well as subjective sleep measures, were analyzed, along with safety outcomes.ResultsTen studies met the inclusion criteria for the systematic review, with five studies contributing to the meta-analysis. The quantitative synthesis comprised 2235 patients in the experimental group and 1409 patients in the control group. Overall, compared with placebo DORAs reduced WASO and LPS while increasing TST after 1 month and 3 months of treatment. Importantly, DORAs increased sTST. Finally, daridorexant showed a favorable safety profile, whereas lemborexant and suvorexant were associated with higher rates of treatment-emergent adverse events than placebo, without an increase in serious adverse events.ConclusionsDespite limited evidence, DORAs appear effective and generally safe for treating CI in the elderly, supporting their role as a valuable therapeutic option.

Abstract licence: CC BY

BackgroundDelirium is a common, serious, and potentially preventable neuropsychiatric syndrome among hospitalized older adults. It is characterized by acute disturbance in attention and awareness with additional cognitive disturbance and a fluctuating course. Dual orexin receptor antagonists (DORAs), including suvorexant, lemborexant, and daridorexant, promote sleep by antagonizing orexin-mediated wakefulness rather than by direct gamma-aminobutyric acid-ergic sedation. Whether DORAs prevent delirium in hospitalized older adults remains uncertain, and prior syntheses have not fully resolved the applicability of this evidence to older inpatients.MethodsWe will conduct a randomized trial systematic review and meta-analysis, if feasible, evaluating DORAs for delirium prevention in hospitalized adults aged 65 years or older. We will search MEDLINE via PubMed, Embase via Ovid, the Cochrane Central Register of Controlled Trials via the Cochrane Library, Web of Science Core Collection, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to the planned final search date, without language or date restrictions. Eligible interventions will include suvorexant, lemborexant, or daridorexant administered before delirium onset. Eligible comparators will include placebo, usual care, no prophylaxis, or clinically interpretable active comparators. The primary outcome will be incident delirium during hospitalization. Secondary outcomes will include delirium severity, duration, subtype, time to onset, sleep-related outcomes, length of stay, mortality, discharge destination, treatment discontinuation, and adverse events. Two reviewers will independently screen records, extract data, assess risk of bias using RoB 2, and judge applicability for the primary quantitative synthesis. Meta-analysis will be performed only when at least two studies are clinically and methodologically sufficiently similar. We will use random-effects models, prespecified sparse-data methods, exploratory trial sequential analysis only if feasible, and GRADE to assess certainty of evidence.DiscussionThis protocol addresses a focused clinical question while explicitly separating formal review inclusion from eligibility for the primary quantitative synthesis. This distinction is intended to prevent clinically indirect evidence, including mixed-age data, post-delirium treatment, unbalanced combination regimens, or unvalidated delirium ascertainment, from being interpreted as practice-changing evidence for prevention in hospitalized older adults.Systematic review registrationPROSPERO CRD420251087526.

Abstract licence: CC BY-NC-ND

AimThis network meta-analysis of randomized controlled trials (RCTs) aimed to investigate which hypnotics are associated with the most favorable sleep architecture and respiratory outcomes in adults with obstructive sleep apnea.MethodsPrimary outcomes included total sleep time (TST) and apnea-hypopnea index (AHI) during TST. Other outcomes were rapid eye movement (REM) sleep time, latency to persistent sleep (LPS), wake after sleep onset (WASO), sleep efficiency (SE), AHI during non-REM or REM sleep, mean peripheral oxygen saturation (SpO2) during TST, mean SpO2 nadir during TST, arousal index (AI), all-cause discontinuation, adverse event-related discontinuation, and incidence of individual adverse events. Effect sizes with 95% confidence intervals were calculated.ResultsThis systematic review included 32 RCTs (n = 1871, average age = 51.60 years, 62.52% male, mean AHI = 23.60). Our network meta-analysis evaluated brotizolam, daridorexant, eszopiclone, flurazepam, lemborexant, nitrazepam, ramelteon, temazepam, triazolam, zaleplon, zolpidem, zopiclone, and placebo. Compared with placebo, lemborexant increased TST, REM sleep time, and SE and decreased LPS and WASO, whereas both daridorexant and zolpidem increased TST and SE and decreased WASO. These three medications demonstrated respiratory safety and discontinuation profiles similar to those of placebo. Eszopiclone increased TST and SE and decreased LPS, WASO, AHI during TST, and AI, but its effects on LPS, WASO, AHI during TST, and AI disappeared in the sensitivity analysis, excluding continuous positive airway pressure titration studies.ConclusionOur network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice.

Abstract licence: CC BY

Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of CID in adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID. Consecutive patients initiating on-label daridorexant at the Sleep Medicine Centre, University Hospital of Rome Tor Vergata were enrolled. Baseline and 30-day follow-up (FU) evaluations included patients’ and CID characteristics, comorbidities, and clinicians’ and patients’ subjective ratings of changes with the Clinical and Patient Global Impression-Improvement scores (CGI-Is and PGI-Is), as well as Insomnia Severity Index (ISI) scores in a subgroup of patients. Sixty-nine patients initiated 50-mg daily dosage. At FU, 58% of both patients and clinicians rated CID as improved on CGI-Is and PGI-Is, with no differences based on comorbidities, sex, or number of previous medications. No significant predictors of CGI-Is and PGI-Is improvement were identified. At FU, ISI scores (n = 24) significantly decreased from 18.25 ± 3.21 to 12.08 ± 6.12 (Z = 8.000; p < 0.001). Of these, eight patients (33.3%) had absence of insomnia symptoms, and no patients reported a worsening in ISI score categories. This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events. Future research on larger cohorts should explore daridorexant potential across diverse patient characteristics.

Abstract licence: CC BY 4.0