Nighttime Temperature Variations May Confound Sleep Medication Deprescribing Studies

In a letter to the editor published in the Journal of Clinical Sleep Medicine, researcher Firas K. Ghanem highlights ambient weather as a critical, measurable confounder that is easily overlooked in mirror-image deprescribing research. Ghanem examines a mirror-image analysis of Japanese health claims data conducted by Matsui and colleagues, which evaluated whether initiating a dual orexin receptor antagonist helped patients reduce their reliance on sleep medications. In that study, 42.1 percent of long-term benzodiazepine or benzodiazepine receptor agonist users reduced their bedtime dose by at least half, and 21.3 percent met the criteria for complete discontinuation after beginning treatment with a dual orexin receptor antagonist. However, both the original study authors and commentators Kolla and Mansukhani acknowledged an inherent methodological constraint: mirror-image study designs cannot exclude time-related confounding.

The correspondence emphasizes that hypnotic medication utilization closely tracks ambient temperature fluctuations. Fourteen years of Korean national health insurance data demonstrated a U-shaped association between nighttime temperatures and prescribed hypnotic dosages, with both unusually warm and unusually cold temperatures linked to higher daily doses. Furthermore, wearable tracking data gathered across 68 countries demonstrate that warmer nights delay sleep onset and shorten overall sleep duration, a finding reinforced by a systematic review showing adverse impacts of heat across various sleep measures. These temperature-driven disruptions have prompted researchers, including Fitton and colleagues, to introduce the term thermosomnia to describe how rising temperatures influence clinical sleep disorders and their ongoing pharmacological management.

According to Ghanem, weather dynamics introduce substantial vulnerability into mirror-image deprescribing evaluations because of the way patient exposure is measured. In the analysis by Matsui and colleagues, pre- and post-treatment bedtime doses were averaged over observation windows ranging from 6 to 12 months, with window duration depending on individual data availability. When an observation window spans less than a full year, it captures only a fragment of the annual temperature cycle. For a participant evaluated over six-month windows before and after starting the new medication, the two comparison periods necessarily encompass opposite halves of the calendar year, creating an inherent seasonal mismatch between baseline and follow-up observations.

Such seasonal discrepancies would only balance out across a study cohort if patient initiation dates were evenly distributed across the calendar and if observation window lengths bore no relationship to calendar time. Ghanem argues that neither assumption is safe in observational practice, noting that hypnotic medications may be initiated preferentially when patient sleep complaints intensify during unseasonal hot or cold spells. In addition, because the available observation windows were bounded by the study period running from April 2019 to March 2024, window duration may itself correlate with calendar time. Given the nonlinear, U-shaped relationship between temperature and dose, the magnitude and directional impact of this potential bias cannot be reliably predicted, raising particular concern for patients aged 65 years and older, a subgroup of only 40 individuals who demonstrated the clearest deprescribing benefit but face greater heat-induced sleep disturbances.

To clarify the validity of reported deprescribing outcomes, the correspondence outlines three specific analytical steps: evaluating the calendar-month distribution of medication initiation dates alongside pre- and post-window lengths, performing a sensitivity analysis restricted strictly to patients with 12-month windows on both sides so that each observation phase covers a complete annual weather cycle, and adjusting model estimates for season of initiation or local nightly temperature data drawn from Japan Meteorological Agency records. Looking beyond retrospective claims analyses, Ghanem suggests that future clinical trials assessing dual orexin receptor antagonist-assisted tapering should incorporate seasonal stratification during randomization and systematically track nighttime ambient temperatures to safeguard against environmental confounding.

Subject of Research: Weather and temperature confounding in hypnotic deprescribing studies

Article Title: Hot nights, cold nights, and hypnotic doses: weather as a hidden confounder in mirror-image deprescribing studies

Article References: Ghanem, F. K. (2026). Hot nights, cold nights, and hypnotic doses: weather as a hidden confounder in mirror-image deprescribing studies. Journal of Clinical Sleep Medicine, 22(1), Article 209. https://doi.org/10.1007/s44470-026-00219-z

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00219-z

Keywords: sleep medicine, hypnotics, deprescribing, dual orexin receptor antagonists, mirror-image studies, ambient temperature, thermosomnia, benzodiazepines, nights, cold, hypnotic, doses