Low-dose sublingual zolpidem tartrate is associated with dose-related improvement in sleep onset and duration in insomnia characterized by middle-of-the-night (MOTN) awakenings.
OBJECTIVE
To evaluate the efficacy and safety of low-dose, sublingual zolpidem tartrate when taken during a scheduled middle-of-the-night (MOTN) awakening in subjects with insomnia characterized by difficulty returning to sleep following MOTN awakenings.


METHODS
Randomized, double-blind, placebo-controlled, 3-way crossover study.


METHODS
Each treatment period consisted of 2 consecutive nights of dosing separated by a washout of 5 to 12 days. Subjects were awakened 4 h after lights out, dosed with sublingual zolpidem tartrate (3.5 mg or 1.75 mg) or placebo, kept awake for 30 min, and then returned to bed for an additional 4 h. Sleep parameters were assessed by polysomnography (PSG) and post-sleep questionnaires.


METHODS
Five sleep laboratories.


METHODS
Adults (24 males, 58 females, mean age 45.9 y) with a diagnosis of DSM-IV primary insomnia and a history of prolonged MOTN awakenings. Baseline difficulties with MOTN awakenings were confirmed by a 10-day screening sleep diary and PSG screening.


RESULTS
Low-dose sublingual zolpidem tartrate demonstrated significant dose-related decreases in latency to persistent sleep and total sleep time (P < 0.001) compared to placebo after MOTN dosing. All subject reports paralleled PSG observations. Neither dose showed next-morning impairment on the DSST or ratings of sleepiness. The 3.5-mg dose produced improvements in reports of sleep quality (P < 0.001), ability to function, and level of refreshed sleep (P < 0.05 for both dosages) compared to placebo. Sublingual zolpidem tartrate lozenges were generally safe and well tolerated.


CONCLUSIONS
Low-dose sublingual zolpidem tartrate may be suitable for treatment of patients who have difficulty resuming sleep after MOTN awakenings.
Roth
Thomas
T
Henry Ford Hospital Sleep Disorders and Research, Detroit, MI 48202, USA. troth1@hfhs.org
Hull
Steven G
SG
Lankford
D Alan
DA
Rosenberg
Russell
R
Scharf
Martin B
MB
D000286:Administration, Sublingual; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D014851:Wakefulness / Q000187:drug effects*; D055815:Young Adult; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem
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