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Sleep Feb 2024Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant,... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant, lemborexant, and daridorexant), focusing on narcolepsy-like symptoms associated with these drugs.
METHODS
Five prominent databases were searched to identify randomized controlled trials (RCTs) on this topic. Primary safety outcomes included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Excessive daytime sleepiness (EDS), sleep paralysis, and hallucinations were categorized as adverse events (AEs)-related narcolepsy-like symptoms.
RESULTS
Eleven RCTs with 7703 patients were included. DORAs were associated with a higher risk of TEAEs (risk ratio [RR], 1.09; 95% confidence interval [CI], 1.03 to 1.15) and treatment-related TEAEs (RR, 1.69; 95% CI: 1.49 to 1.92) when compared to placebo. The DORA group exhibited a significantly higher risk of EDS (RR, 2.15; 95% CI: 1.02 to 4.52) and sleep paralysis (RR, 3.40; 95% CI: 1.18 to 9.80) compared to the placebo group.
CONCLUSION
This meta-analysis achieved a comparative evaluation of the clinical safety and tolerability of FDA-approved DORAs for primary insomnia, specifically focusing on AEs-related narcolepsy-like symptoms. This study contributes to understanding the safety profile of FDA-approved DORAs for treating insomnia.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Orexin Receptor Antagonists; Sleep Paralysis; Narcolepsy
PubMed: 37950346
DOI: 10.1093/sleep/zsad293 -
Sleep Medicine Reviews Oct 2023Obstructive sleep apnea (OSA) is prevalent in patients with neurodegenerative diseases and is associated with worse outcomes. Positive airway pressure therapy has the... (Review)
Review
Obstructive sleep apnea (OSA) is prevalent in patients with neurodegenerative diseases and is associated with worse outcomes. Positive airway pressure therapy has the potential to benefit these patients but can be challenging in this population. Our primary aim was to describe positive pressure therapy adherence. Secondarily, we aimed at identifying identify predictors of adherence to treatment in adults with neurodegenerative diseases and OSA, and report the effect of PAP adherence on outcomes such as cognitive function, quality of life and patient/caregiver satisfaction. We performed a systematic review of the literature and identified seventeen studies, eight reporting on adults with obstructive sleep apnea and mild cognitive impairment (MCI) and/or Alzheimer's disease (AD), 6 with Parkinson's disease (PD), and 3 with multiple system atrophy (MSA). Meta-analyses were not performed due to lack of systematic and standardized reporting of the primary outcome. Study duration ranged from 6 weeks to an average of 3.3 years. PAP adherence definition was widely variable between studies. Attrition rates ranged from 12% to 75%. In MCI/AD, adherence rates ranged from 28% to 61% (study duration range: 3 weeks to 3.3 years). Younger age, race (white) and better CPAP confidence scores at 1 week were associated with more CPAP use while APOE4 positive and unmarried individuals were more likely to abandon CPAP. In most studies, adherent patients had improvement in excessive daytime sleepiness, depressive symptoms, sleep quality, ability to manage daily activities and certain aspects of cognition (composite score or global cognition, psychomotor speed, executive function), as well as less cognitive decline over time. Caregiver satisfaction was also better in PAP adherent patients in one study. In PD, 15-25% of individuals refused treatment with PAP upfront, and attrition ranged from 8 to 75%. Adherent patients used their device for an average of 3h27 to 5h12 per night (study duration range: 6 weeks to 12 months). Longer disease duration, worse motor symptoms or sleep quality and lower % of REM sleep were identified as predictors of lower PAP adherence in a preliminary study, while race (non-white) and sex (women) were linked to lower adherence in a large retrospective study. In the study reporting the highest attrition rate (75%), individuals had lower educational levels. PAP adherence improved daytime sleepiness, anxiety symptoms, sleep architecture and quality and global non-motor symptoms. However, in one short-term (3 weeks) study, there was no improvement in neuropsychological testing composite score. Three studies on MSA patients suffering from sleep-disordered breathing showed that most patients are accepting of PAP (69-72%) with an average nightly use of 4h42 to 6h18. Floppy epiglottis was more frequently seen in patients discontinuing PAP in one study. In one study, four adults with MSA and long-term PAP use reported better sleep and improved vigilance. Survival time was no different between treated and untreated individuals. In conclusion, PAP therapy is challenging in patients with OSA and NDD, as evidenced by the considerable attrition and low adherence rates reported in this systematic review. There is emerging evidence proposing OSA a treatable target to prevent clinical and functional deterioration in patients with neurodegenerative diseases and addressing potential barriers to PAP adherence is paramount to maximize adherence. Our systematic review outlines several of these potential barriers, underscoring the need for future studies to standardize the definition of and explore long-term adherence to PAP therapy and assess interventions that can optimize adherence in this patient population.
Topics: Adult; Humans; Female; Infant, Newborn; Continuous Positive Airway Pressure; Quality of Life; Retrospective Studies; Sleep Apnea, Obstructive; Parkinson Disease; Disorders of Excessive Somnolence; Patient Compliance
PubMed: 37586145
DOI: 10.1016/j.smrv.2023.101836 -
Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008