Sublingual and oral zolpidem for insomnia disorder: a 3-month randomized trial

Abstract

Objective: To evaluate the safety and efficacy of a 5 mg sublingual dose of zolpidem, compared to a 10 mg oral dose, at bedtime and ''as needed'' following middle-of-the-night awakenings. Methods: Participants were randomized into an oral group (oral zolpidem 10 mg and sublingual placebo at bedtime and ''as-needed'') and a sublingual group (oral placebo and sublingual zolpidem 5 mg at bedtime and ''as-needed''). Participants underwent medical evaluation, polysomnography, the psychomotor vigilance test, and completed questionnaires. Results: Of 85 patients, 67 met the criteria for insomnia (48610 years; 79% women) and were randomized. Of these, 46 completed 9265 days of treatment. Mild-to-moderate adverse events were reported by 25% of the participants, including headache, sleepiness, and dizziness. Both treatments decreased middle-of-the-night awakenings by an average of-3.162.3 days/week and increased total sleep time by 1.5 hours. Changes in sleep quality and insomnia severity scores were also favorable and comparable between groups: variation depended on continuation of treatment. Regarding PSG findings, sleep latency decreased more in the sublingual group than the oral group (-14642 vs. 10629 min; p = 0.03). The psychomotor vigilance test showed minor residual effects 30 minutes after awakening, which reversed after 2 hours. Conclusions: The safety and efficacy of both zolpidem formulations are comparable. The sublingual 5 mg dose induced sleep more rapidly. Clinical trial registration: NCT01896336

Efficacy, Safety, and Drug–Drug Interactions for Insomnia Therapy in COVID-19 Patients

“…However, the sublingually formulated Zolpidem has the ability for faster absorption and distribution, thus achieving higher concentrations and inducing sleep more quickly. 16 Lorediplon 10 mg progressively reduces WASO during the first three-quarters of the night. Lorediplon showed a dose-dependent increase in sleep, whereas Zolpidem showed a more sustained WASO effect.…”

“…Meanwhile, the lowest SE occurred in sublingual Zolpidem, which only increased sleep efficiency by 3% from baseline. [14][15][16] Safety Safety studies were analyzed in the same study as efficacy. The most frequently reported side effects are non-serious, ranging from mild to moderate.…”

Orexin dual receptor antagonists, zolpidem, zopiclone, eszopiclone, and cognitive research: A comprehensive dose-response meta-analysis

“…Zopidem has minor sequelae, tolerance, drug dependence and withdrawal symptoms, and a wide range of safety (Holm and Goa, 2000 ). However, when used with other central inhibitors, it can cause severe respiratory depression (Castro et al, 2020 ). It is suitable for occasional and temporary insomnia.…”

2023 Guidelines on the Diagnosis and Treatment of Insomnia in Adults – Brazilian Sleep Association

“…131 In individuals with chronic insomnia, oral (10mg) and sublingual (5mg) zolpidem led to a similar reduction in the number of wakes and an increase in TST, but with a greater reduction in sleep latency with sublingual zolpidem. 132 For maintenance insomnia, with nighttime wakes, sublingual zolpidem (5 mg) increased TST, without significant changes in sleep latency, WASO, or sleep quality, and with sleepiness and reduced alertness in the morning. 133 Extended-release zolpidem (12.5 mg), in individuals with chronic insomnia, increased TST and sleep efficiency, while reducing latency to persistent sleep, wakes, and WASO.…”

“…Side effects of zolpidem include sleepiness (5%), dizziness (5%), headache (3%), gastrointestinal symptoms (4%), sleepwalking (1%), nightmares (1-2%), and mental confusion (1-2%). 128,131,132,135 The risk of falls and fractures is increased, especially among older people. 128 Non-REM (NREM) sleep parasomnias, and behavioral changes (disinhibition, aggressiveness, impulsivity, visual and auditory hallucinations, driving) are possible effects, more prevalent in association with alcohol.…”