Effects of zolpidem on cyclic alternating pattern, an objective marker of sleep instability, in Japanese patients with psychophysiological insomnia: a randomized crossover comparative study with placebo.
OBJECTIVE
A placebo-controlled randomized crossover study to investigate the effects of zolpidem on sleep stability in Japanese insomniac patients was performed using the cyclic alternating pattern (CAP) rate, a polysomnographic marker that reflects sleep instability.


METHODS
Seventeen patients (5 M and 12 F, mean age: 40.4+/-13.6 years) who met the International Classification of Sleep Disorders (ICSD) criteria for psychophysiological insomnia were evaluated. During the first period, patients were administered the placebo on the first night, followed by either zolpidem or the placebo on the second night (treatment night). The second crossover period was conducted after a minimum 3-day observation. Improvement in the overnight CAP rate was the primary endpoint. Secondary endpoints included the CAP variables, conventional sleep variables, EEG arousals, subjective evaluation of sleep quality (measured by means of a visual analogue scale and the St. Mary's Hospital Sleep Questionnaire), and drug safety.


RESULTS
Zolpidem significantly decreased the overnight CAP rate values (57.6 vs. 39.0%, p=0.009) and improved "sleep depth" (p=0.044) and "sleep quality" (p=0.023) subjective questionnaire scores. Zolpidem also significantly improved VAS (p=0.036). The amount of time spent in sleep stages 3+4 was significantly increased by zolpidem without affecting the amounts of stage 2 and rapid eye movement (REM) sleep. Significant negative correlations were found when the sleep quality score was matched to the CAP rate (p=0.022). No serious adverse events occurred during the study.


CONCLUSIONS
In Japanese patients with psychophysiological insomnia, zolpidem increased sleep stability by significantly improving the overnight CAP rate. Zolpidem also improved sleep depth and sleep quality, both subjectively and objectively.
Ozone
M
M
Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan. ozone@jikei.ac.jp
Yagi
T
T
Itoh
H
H
Tamura
Y
Y
Inoue
Y
Y
Uchimura
N
N
Sasaki
M
M
Shimizu
T
T
Terzano
M G
MG
Parrino
L
L
D000328:Adult; D000367:Age Factors; D001143:Arousal / Q000187:drug effects; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017286:Polysomnography / Q000379:methods; D011725:Pyridines / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D012894:Sleep Stages / Q000187:drug effects*; D013223:Statistics as Topic; D011795:Surveys and Questionnaires; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem