Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects — and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Cipriani said.

The findings were published online July 16 in The Lancet.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference [SMD] range, 0.36 to 0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27 to 0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.

From Medscape Medical News