In a comprehensive comparative-effectiveness analysis that was published online in The Lancet., lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.
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. However, eszopiclone may cause substantial side effects and safety data on lemborexant were inconclusive, the researchers note.
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 apply for licensing insomnia drugs,” Cipriani said.
Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity. Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.
However, insomnia drugs are not all created equal. Even within the same drug class there are differences, Cipriani said.
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, that 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 the 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 the 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.
The researchers reported that their little long-term data suggests eszopiclone and lemborexant are more effective than placebo. They also reported that eszopiclone is more effective than ramelteon and zolpidem, but with “very low” certainty of the evidence.