Review: benzodiazepines and zolpidem are effective for chronic insomnia
Evidence-Based Mental Health
Nowell PD, Mazumdar S, Buysse DJ, et al. Benzodiazepines and zolpidem for chronic insomnia. A meta-analysis of treatment efficacy. JAMA 1997 Dec 24/31;278:2170-7. 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
... ; 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 Unpublished studies and studies reported in abstracts, dissertations, theses, or book chapters were excluded.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). Conclusion 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. Commentary Nowell et al have published a thorough meta-analysis on the pharmacological treatment of chronic insomnia (ie, sleep complaints for >1 mo). Their review shows that this kind of treatment produces a substantial improvement in periods <5 weeks. The available evidence resulting from this review, however, is limited for healthcare practice. Firstly, no uniform criteria for the diagnosis of chronic (primary) insomnia were used in the studies reviewed; 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 insom-nia 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 behavioural interventions can offer lasting benefits to patients with chronic insomnia. This review shows that behavioural treatments produce reliable and durable (ie, improvements 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 effective single treatment procedures, whereas sleep hygiene education was not effective when used alone. No sound studies are available in which long term pharmacological treatments in chronic insomnia have been compared with behavioural ones. To date, although hypnotics are effective for the treatment of acute insomnia, their role in the long term treatment of chronic insomnia remains unclear. Whether hypnotics and behavioural therapy work better in tandem or separately is not known. 3 1 Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment. Prevalence and correlates. Arch Gen Psychiatry 1985;42:225-32. 2 Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry 1994;151:1172-80. 3 Lamberg L. Sleep specialists weigh hypnotics, behavioral therapies for insomnia. JAMA 1997;278:1647-9. Benzodiazepines and zolpidem v placebo for chronic insomnia Outcomes Number of studies Weighted effect size 95% CI Controls with a worse outcome than treated* Sleep onset latency 9 0.56 0.41 to 0.71 71% Total sleep time 9 0.71 0.55 to 0.87 76% No of awakenings 6 0.65 0.48 to 0.82 74% Sleep quality 5 0.62 0.45 to 0.79 73% *The proportion of patients treated by placebo for which the average treated patient had a better outcome.