Intermittent dosing of zolpidem with placebo after one month of full dose nightly zolpidem is an effective acute and extended treatment for patients with chronic insomnia while using 50% less medication, according to study results published in Sleep Medicine.

Prior studies have shown that for chronic insomnia, intermittent dosing approach is comparable to nightly dosing. However, the data to support intermittent dosing are limited. Previously, the researchers evaluated a modified intermittent dosing regimen with placebo given on non-medication nights, based on the principles of conditioning and reinforcement. The data suggested that with the partial reinforcement regimen, including a month of full dose nightly treatment with zolpidem (priming), subjects with chronic insomnia who switched to intermittent dosing with medication and placebos were able to maintain their treatment responses.

The objective of the current study was to determine whether priming is required for partial reinforcement or whether intermittent dosing with placebos can be used for acute and extended treatment.

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The study included 4 phases: baseline assessment of sleep continuity (Phase-1), nightly dosing with standard dose of zolpidem or intermittent dosing with placebos for 30 days (Phase-2), re-randomization of participants treated with standard dose of zolpidem to either continuous nightly dosing or intermittent dosing with placebos administered on non-medication nights for 90 days (Phase-3). 

The study sample included patients aged 40 years and older with chronic insomnia recruited from the local sleep disorders center, from advertisements and via social media. Of 99 patients enrolled into Phase-1, 44 subjects were lost to follow-up. Overall, 55 patients (mean age, 61.2 years; 64% women) were enrolled into Phase-2, and 37 were included in Phase-3.

There were no significant differences in treatment responses (77% vs. 50%, respectively; P =.09) or changes in total wake time (-43 min vs. -76 min, respectively; P =.35) between continuous and intermittent treatment, suggesting the outcomes were similar with 50% less medications.

A total of 37 patients continued on to Phase-3, including 15 patients randomized to continuous nightly dosing, 14 patients randomized to continuous nightly dosing followed by intermittent dosing, and 8 patients randomized to intermittent dosing all along. Continued treatment responses were observed in 73%, 57%, and 88% of patients, respectively (P =.22), while the mean improvement of total wake time continued with continuous nightly dosing and remained stable for the other 2 groups.

The study’s main limitation included its small sample size.

“These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment,” the researchers concluded.


Perlis ML, Morales KH, Vargas I, et al. Durability of treatment response to zolpidem using a partial reinforcement regimen: does this strategy require priming? Sleep Med. Published online August 21, 2021. doi: 10.1016/j.sleep.2021.04.041

This article originally appeared on Neurology Advisor