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Review: benzodiazepines and zolpidem are effective for chronic insomnia
  1. Alex van Bemmel, MD, PhD
  1. Uniersity of Maastricht Maastricht, the Netherlands

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Question What is the efficacy of benzodiazepines and zolpidem tartrate in patients who have chronic insomnia?

Data sources

Studies were identified by searching Medline (1966–96) using the keywords insomnia, drug therapy, and placebos; searching Current Contents; handsearching the Journal of Sleep Research up to 1995; and scanning bibliographies of relevant studies.

Study selection

Studies were selected if they were published in English; involved patients who were ≤65 years of age with primary insomnia according to criteria that were compatible with those specified in DSM-IV; were randomised, double blind, placebo controlled trials; and used benzodiazepines and zolpidem in clinical settings in the US. Unpublished studies and studies reported in abstracts, dissertations, theses, or book chapters were excluded.

Data extraction

Data were extracted on age, sleep measures, and treatment duration by 1 investigator. Data for study outcomes (self reported and polysomnographic measures for sleep onset latency, total sleep time, number of awakenings, and sleep quality) were extracted using consensus by 2 investigators.

Main results

22 studies, which were published from 1978–96 and involved 1894 mostly middle aged patients (approximately 60% women), met the inclusion criteria. 9 studies involving 680 patients with primary insomnia (n=343 medication group, n=337 control group) reported sufficient data to calculate effect sizes for 1 of the 4 outcomes. Meta-analytical techniques were used to calculate standardised mean differences. The median duration of treatment was 7 days (range 4–35 days). Medications included flurazepam hydrochloride, 30 mg (4 studies); temazepam, 30 mg (1 study) and 20 mg (1 study); zolpidem tartrate, 10 mg (2 studies); and estazolam, 2 mg (1 study). Patients who received benzodiazepines and zolpidem fell asleep faster, slept longer, woke less often, and reported better sleep quality than patients who received placebo (p<0.001 for all comparisons) (table). Statistically significant heterogeneity did not exist across studies. Temazepam and zolpidem had the largest effect sizes for sleep onset latency (0.78 and 0.77, respectively) and flurazepam, temazepam, and estrazolam had the largest effect sizes for total sleep time (0.84, 0.71, and 0.67, respectively).

Benzodiazepines and zolpidem v placebo for chronic insomnia


For patients who have chronic insomnia, benzodiazepines and zolpidem are effective in reducing sleep onset latency, increasing total sleep time, reducing the number of awakenings, and improving sleep quality.


Nowell et al hae published a thorough meta-analysis on the pharmacological treatment of chronic insomnia (ie, sleep complaints for ≥1 mo). Their reiew shows that this kind of treatment produces a substantial improement in periods ≤5 weeks. The aailable eidence resulting from this reiew, howeer, is limited for healthcare practice. Firstly, no uniform criteria for the diagnosis of chronic (primary) insomnia were used in the studies reiewed; secondly, the authors did not find studies that systematically measured daytime functioning, which is mostly impaired in chronic insomnia; thirdly, no sound longitudinal studies beyond 5 weeks of treatment were included, whereas it has been estimated that 11% of patients with chronic insomnia use hypnotics regularly for >1 year;1 and fourthly, no clear uniform definitions of treatment response were found in the selected studies.

According to another meta-analysis,2 behaioural interentions can offer lasting benefits to patients with chronic insomnia. This reiew shows that behaioural treatments produce reliable and durable (ie, improements maintained at a mean follow up of 6 mo) changes in the sleep patterns of patients with chronic insomnia.2 Stimulus control and sleep restriction were the most effectie single treatment procedures, whereas sleep hygiene education was not effectie when used alone. No sound studies are aailable in which long term pharmacological treatments in chronic insomnia hae been compared with behaioural ones. To date, although hypnotics are effectie for the treatment of acute insomnia, their role in the long term treatment of chronic insomnia remains unclear. Whether hypnotics and behaioural therapy work better in tandem or separately is not known.3



  • Source of funding: in part, National Institute of Mental Health.

  • For correspondence: Dr P D Nowell, Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15215, USA. Fax +1 603 650 7820.

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