Pilot Controlled Double-Blind Study of the Hypnotic Effects of Zolpidem in Patients with Chronic ‘Learned’ Insomnia: Psychometric and Polysomnographic Evaluation

Abstract

In a pilot double-blind trial in 21 patients with learned or idiopathic insomnia (DSM-IIIR), patients received placebo for 1 week (nights 1-7), either active (zolpidem, 10 mg) or placebo treatment for 2 weeks (nights 8-21) and then placebo for a further week (nights 22-28). Variables to measure efficacy, rebound and withdrawal were assessed daily from day 1 to day 28. Polysomnographic recordings together with sleep cycle analysis were performed on nights 7, 21 and 28. Patients treated with 10 mg zolpidem for 2 weeks had significantly improved sleep efficiency at the end of the randomised double-blind phase compared with the placebo group. Fractionated sleep-cycle analysis showed an increase in slow-wave sleep during the first 2-hour cycle after sleep onset. During the withdrawal placebo week, most of the main sleep variables remained relatively stable in the zolpidem group (nights 22-28), and deteriorated further in the placebo group. At the end of the withdrawal phase, there was a statistically significant difference between groups, in favour of the zolpidem treatment, in sleep efficiency, total sleep time, absolute and percentage of time awake, and percentage of REM sleep. REM sleep, which was normal in both groups at baseline, decreased significantly in the placebo group between nights 22 and 28 (during the withdrawal placebo week) compared with the zolpidem treatment group, and the number of periods of time awake increased. Minor subjective complaints were recorded under zolpidem and were comparable with those under placebo. Zolpidem seemed to improve some important sleep variables, when assessed both objectively and subjectively. The sleep cycle analysis suggested a possible shift of slow-wave sleep to an earlier period of the night, with a more physiological sleep structure. There was no evidence for withdrawal or rebound after stopping the 2 weeks of zolpidem treatment, but rather signs that the effect of zolpidem outlasted active treatment. The present pilot study justifies a prospective confirmatory comparison of zolpidem with benzodiazepines in an adequate number of patients and withdrawal after 6-8 weeks of treatment.

0395 Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline

“…In addition, one paper evaluated the effectiveness of zolpidem extended release 6.25 mg 80 and one paper assessed zolpidem extended release 12.5 mg. 81 Five studies examined the effects of zolidem 10 mg on objective sleep latency. 60,73,76,77,82 The mean reduction (vs. placebo) for PSG-determined latency to sleep exceeded the threshold for clinical significance. Ten studies presented patient-reported sleep latency data.…”

“…57,59,60,70,[72][73][74][75][76][77][78][79] The overall quality of evidence was downgraded to very low due to significant heterogeneity, imprecision, and risk of publication bias. The evidence for zolpidem 10 mg was weakly in favor of its effectiveness for improving sleep onset, sleep maintenance, sleep quality, SE and TST.…”

“…57,60,70,[72][73][74][75][76]78,82 The mean reduction in subjective latency fell approximately at the significance threshold. Two studies 73,76 reported adequate objective TST data for metaanalysis and found that the mean improvement in TST also exceeded the clinical significance threshold. The same was true for subjective TST, based on eight studies.…”

“…The same was true for subjective TST, based on eight studies. 57,70,[73][74][75][76]78,82 Two studies 73,76 found that PSG-determined reduction in WASO was clinically significant. Six studies included adequate data for meta-analysis of subjective WASO 57,72,75,76,78,82 ; the mean reduction fell below the clinical significance threshold.…”

Zolpidem, a Valuable Alternative to Benzodiazepine Hypnotics for Chronic Insomnia?

“…7 Zolpidem has a rapid onset of action and does not negatively affect physiological 254 sleep architecture.!? - 12 It has been observed that cessation of zolpidem treatment does not induce significant rebound insomnia or withdrawal manifestations.w-> It is not known whether treatment of insomnia with a non-benzodiazepine such as zolpidem induces a more natural sleep in patients with chronic insomnia, after the cessation of long-term use of benzodiazepines. Discontinuation of longterm benzodiazepines can be difficult owing to rebound and/or withdrawal symptoms, which leads to chronic use and dependency in some patients."…”