Requested DocAlert: Standard Hypnotics Help, but Do Not Cure, Insomnia


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Standard Hypnotics Help, But Do Not Cure, Insomnia

In real-world patients with insomnia and comorbidities, benzodiazepine receptor agonists led to improvement in most but to remission in few.

Sleep disturbance is a major symptom of many psychiatric illnesses and benzodiazepine receptor agonists (BzRAs) are liberally used for treatment, supported by randomized, controlled studies showing that BzRAs “work” better in selected patients than placebo. In a large, real-world sample of 193 patients with insomnia, most with psychiatric (50%) and medical (74%) comorbidities, researchers with industry funding have now examined how well BzRAs actually work for insomnia symptoms, as measured on a standard scale with patients retrospectively rating sleep initiation and maintenance problems.

Most patients were taking zolpidem (71%; half were taking 10-mg doses); temazepam (11%) and eszopiclone (7%) were the next most frequently used BzRAs. About 28% of patients were taking antidepressants; 14% took additional hypnotics. Median BzRA use was daily (mean, 5 times weekly).

Compared with insomnia scores without BzRA use, scores with BzRA use improved but stayed in the clinically significant range for sleep disturbance. Although 77% of patients were responders, only 48% achieved remission. Dose was unrelated to efficacy. Medical comorbidity predicted lower likelihood of response, and medical or psychiatric comorbidity predicted lower likelihood of remission.


This study shows that standard hypnotic agents are not fully effective for insomnia, especially in people with medical or psychiatric comorbidity, and suggests that most efficacy studies of these agents captured response but not remission. How much did the failure to treat the comorbid psychiatric condition contribute to poorer remission? We cannot know. Given these results, clinicians should more regularly consider the effective treatment, insomnia-focused cognitive behavioral therapy (NEJM JW Psychiatry Sep 2015 and JAMA Intern Med 2015; 175:1461), for their patients with nonremitting insomnia.

Peter Roy-Byrne, MD reviewing Pillai V et al. Sleep 2016 Dec 26.

Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Pillai V et al. Effectiveness of benzodiazepine receptor agonists in the treatment of insomnia: An examination of response and remission rates. Sleep 2016 Dec 26; [e-pub].
[PubMed® abstract]

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