Chlormethiazole as a hypnotic in elderly patients: A systematic review and meta-analysis

The study objective was to estimate the efficacy and safety of chlormethiazole in older adults experiencing insomnia (sleep disorder). We therefore systematically searched Medline, Scopus, the Cochrane Library, PsycINFO, Ovid, ZB MED and PMC through December 2021 for randomized-controlled trials including patients > 60 years old with insomnia treated with chlormethiazole. Standardized mean differences or odds ratios with 95% confidence intervals were calculated for the main outcome parameters: sleep duration, onset of sleep, quality of sleep, adverse events or drop-out rates compared with placebo and other drugs. Risk of bias was assessed using the Cochrane tool. Eight randomized-controlled trials with 424 patients were included. Chlormethiazole significantly increased the duration of sleep when compared with placebo (standardized mean difference = 0.61; 95% confidence interval = 0.11-1.11; p = 0.02). More patients receiving chlormethiazole had adequate quality of sleep than those receiving other drugs (odds ratio = 1.44; 95% confidence interval = 1.04-1.98; p = 0.03). No differences were found regarding the onset of sleep (standardized mean difference = 1.07; 95% confidence interval = 0.79-1.46; p = 0.65). Drop-out rates were significantly lower under chlormethiazole treatment when compared with other drugs (odds ratio = 0.51; 95% confidence interval = 0.26-0.99; p = 0.05) and did not differ from placebo treatment (odds ratio = 1.37; 95% confidence interval = 0.23-8.21; p = 0.73). Side-effects such as "hangover" and daytime drowsiness occurred less frequently during chlormethiazole treatment compared with other drugs in three out of four studies, but differences were not significant (odds ratio = 0.24; 95% confidence interval = 0.04-1.48; p = 0.12). In conclusion, chlormethiazole showed significant effects on the duration and the quality of sleep with better tolerability if compared with other drugs in older adults with insomnia.