Novel Sublingual Low-Dose Zolpidem Tablet Reduces Latency to Sleep Onset following Spontaneous Middle-of-the-Night Awakening in Insomnia in a Randomized, Double-Blind, Placebo-Controlled, Outpatient Study

作者：Roth Thomas^*; Krystal Andrew; Steinberg Frank J; Singh Nikhilesh N; Moline Margaret

来源：Sleep, 2013, 36(2): 189-196.

DOI：10.5665/sleep.2370

• Insomnia
• middle-of-the-night awakenings
• MOTN insomnia
• pharmacotherapy
• zolpidem

Study Objectives: To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the-night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings.
Design: Multicenter randomized, double-blind, placebo-controlled, parallel-group.
Setting: Outpatient.
Patients: There were 295 adults (median age 43 y; 68.1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTN awakenings/wk during screening).
Interventions: After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures.
Results: ZST significantly (P < 0.0001) decreased latency to sleep onset over 4 wk (baseline 68.1 min; ZST 38.2 min) compared with placebo (baseline 69.4 min; placebo 56.4 min). Ratings of morning sleepiness/alertness significantly (P = 0.0041) favored the ZST group on nights medication was taken but not on other nights. Participants in the ZST group took the study drug on 62% of nights during the 4 wk; members of the placebo group took study medication on 64% of nights. Adverse events were generally mild and at the same rate (19.3% of participants) in both groups. There were no treatment-related serious adverse events (SAEs), and one adverse event-related study discontinuation from the placebo group. Dosing/week did not increase across the study.
Conclusions: 3.5 mg ZST used as needed significantly reduced latency to return to sleep in comparison with placebo in these patients with insomnia. Sleep quality was improved, and morning sleepiness/alertness scores also improved. ZST was well tolerated. These data demonstrate the utility of a sleep-promoting agent when used as needed in the MOTN.

• 出版日期2013-2-1