suvorexant and Sleep-Apnea--Obstructive

Insomnia and hypersomnia are conditions with multifactorial causes that can be difficult to treat. There have been recent developments and changes in the treatment of both conditions, including the addition of some agents that have a novel mechanism of action. This review summarizes recent changes and highlights pertinent updates.. Benzodiazepine receptor agonists received a warning in 2019 regarding the possibility of complex sleep behaviors, such as sleepwalking. Zolpidem has been marketed in new dosage forms that include sublingual tablets and oral spray formulations. Orexin receptor antagonists appear to be well tolerated with a good safety profile. Suvorexant received an approval for the treatment of patients with comorbid insomnia and dementia. Lemborexant was demonstrated to be effective for maintenance insomnia. Trazodone was shown to affect the oligomerization of tau proteins thus suggesting potential implications in attenuating dementia pathology. Pitolisant, a novel histamine-3 receptor antagonist/inverse agonist, gained approval for the treatment of excessive daytime sleepiness in adults with narcolepsy as well as obstructive sleep apnea. Solriamfetol, a new norepinephrine and dopamine reuptake inhibitor, was approved for hypersomnolence based on good efficacy, but with cardiovascular warnings.. Recent advancements in the treatment of insomnia includes agents with novel mechanisms, new indications, and new dosage forms. Risk of complex sleep behaviors, and possible next-day driving impairment, should be discussed for all agents used for insomnia, including orexin receptor antagonists. Novel agents also are available for hypersomnia and there are options beyond traditional stimulants that may have great utility.

Topics: Azepines; Carbamates; Dementia; Disorders of Excessive Somnolence; GABA-A Receptor Agonists; Humans; Orexin Receptor Antagonists; Phenylalanine; Piperidines; Pyridines; Pyrimidines; Sleep Aids, Pharmaceutical; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Trazodone; Triazoles; Zolpidem

To investigate the respiratory effects of suvorexant, an orexin receptor antagonist for treating insomnia, in patients with obstructive sleep apnea (OSA).. This was a randomized, double-blind, placebo-controlled, 2-period (4 days per period), crossover, sleep laboratory study. Twenty-six patients aged 18-65 years with mild (apnea-hypopnea index [AHI] ≥ 5 and < 15) to moderate (AHI ≥ 15 and < 30) OSA were randomized to receive suvorexant 40 mg or placebo in period-1 and then crossed over to the other treatment in period-2. Breathing during sleep was measured by AHI (primary endpoint) and oxygen saturation assessed by pulse oximetry (SpO2, secondary endpoint). The study was powered to rule out a mean increase in AHI between suvorexant and placebo of 5 or greater on Day 4.. There was a small increase in mean AHI (2.66) in OSA patients after multiple doses of suvorexant relative to placebo, with the upper 90% CI bound slightly exceeding 5.00 (0.22, 5.09). No increase in mean AHI was observed after a single dose of suvorexant versus placebo (mean difference = -0.47 [-3.20, 2.26]), and there was no treatment effect on mean SpO2 during total sleep time after single or multiple doses (Day 1: mean difference = -0.04 [-0.49, 0.42]; Day 4: mean difference = -0.06 [-0.45, 0.33]). There was inter- and intra-individual variability in suvorexant respiratory effects.. Suvorexant 40 mg, twice the 20 mg maximum recommended dose for treating insomnia in the USA and Japan, does not appear to have clinically important respiratory effects during sleep in patients with mild to moderate OSA as assessed by mean AHI and SpO2. Due to inter- and intra-individual variability in respiratory effects, suvorexant should be used with caution in patients with compromised respiratory function, and at the lowest effective dose.. clinicaltrials.gov, NCT01300455.

Topics: Adolescent; Adult; Aged; Azepines; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Orexin Receptor Antagonists; Polysomnography; Respiration; Sleep; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Triazoles; Young Adult

Although patients with suspected obstructive sleep apnea (OSA) might suffer difficulty in falling asleep during overnight polysomnography (PSG), standard hypnotics to obtain sleep during PSG have not been established. The aim of this study was to investigate the safety and efficacy of a new hypnotic agent, suvorexant, a dual orexin receptor antagonist, for insomnia in suspected OSA patients during in-laboratory PSG.. An observational study was conducted during PSG for 149 patients with suspected OSA who had no insomnia at home. Patients with difficulty in falling asleep during PSG were optionally permitted to take single-use suvorexant. Patients with residual severe insomnia (>1 hour) after taking suvorexant were permitted to take an add-on use zolpidem. Clinical data and sleep questionnaire results were analyzed between a no insomnia group (without hypnotics) and an insomnia group (treated with suvorexant).. Among 84 patients who experienced insomnia during PSG and required hypnotics (the insomnia group; treated with suvorexant), 44 (52.4%) achieved sufficient subjective sleep with single-use of suvorexant, while the other 40 (47.6%) required suvorexant plus zolpidem. An apnea hypopnea index (AHI) of ≥5 was observed in 144 out of 149 patients with predominantly obstructive respiratory events. Among those patients, 70.8% in the no insomnia group and 63.1% in the insomnia group had severe OSA. Regarding both subjective sleep time and morning mood, significant differences between the no insomnia group and the insomnia group were not observed. No patient taking suvorexant had an adverse event, such as delirium or falling.. Single-use suvorexant seems to be a safe and effective (but mild) hypnotic agent for suspected OSA patients with insomnia during in-laboratory PSG.

Topics: Azepines; Humans; Polysomnography; Sleep Aids, Pharmaceutical; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Triazoles