A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo.
OBJECTIVE
To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers.


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


METHODS
Single research center.


METHODS
Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days.


RESULTS
Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments.


CONCLUSIONS
Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.
Hindmarch
Ian
I
HPRU Medical Research Centre, University of Surrey, School of Biomedical & Molecular Sciences, Egerton Road, Guildford, UK.
Dawson
Jean
J
Stanley
Neil
N
D000293:Adolescent; D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage / Q000494:pharmacology*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D015992:Body Mass Index; D004311:Double-Blind Method; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D000069583:Pregabalin; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects*; D011795:Surveys and Questionnaires; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000525:Alprazolam