A new study led by researchers from the University of Oxford has reviewed more than 150 clinical trials to present a comprehensive, comparative analysis of 30 different drug treatments for insomnia. The findings indicate many common insomnia drugs lack long-term safety data and popular treatments such as melatonin have little clinical evidence of effectiveness.

“We looked at all information published and unpublished – in journals and in online registries – to achieve the most transparent and comprehensive picture of all the data available,” explained Andrea Cipriani, who led the research. “Clearly, the need to treat insomnia as effectively as possible is very important, as it can have knock-on effects for a patient’s health, their home lives and the wider health system.”

The study included data from 154 double-blind, randomized controlled trials, encompassing more than 44,000 people. Thirty different pharmacological treatments for insomnia were examined, with effectiveness and side effects tracked for both acute and long-term usage.

The ultimate findings pointed to two particular drugs demonstrating the most effective treatment profiles: lemborexant and eszopiclone. And more common insomnia treatments such as benzodiazepines and zolpidem were found to be helpful in the short-term, but lacked evidence for long-term efficacy or safety.

“Considering all the outcomes at different timepoints (ie, acute and long-term treatment), lemborexant and eszopiclone had the best profile in terms of efficacy, acceptability, and tolerability; however, eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive,” the study concluded.

Interestingly, both lemborexant and eszopiclone are yet to be approved in the European Union. Lemborexant in particular is a new kind of insomnia drug, only approved for use in the United States in 2019. Philip Cowen, co-author on the study, said the mechanism of action used by lemborexant may be improved in the future for better insomnia medications.

“It should also be noted that the drug lemborexant acted via a different pathway in the brain (the orexin neurotransmitter system), a relatively novel mechanism of action,” Cowen explained. “More selective targeting of this pathway and orexin receptors could lead to better pharmacological treatments for insomnia.”

The study also found the popular insomnia treatment melatonin had poor efficacy data and little long-term study. The lack of long-term data on insomnia drugs in general was highlighted in the study as a problem considering the condition is often persistent, requiring treatment for extended periods of time.

Cipriani does make clear this study only focused on pharmacological interventions for insomnia. Behavioral and lifestyle interventions were not included in the comparative review, so these alternative methods should always be considered either before, or alongside, any drug treatment.

“This study of pharmacological treatments is not a recommendation that drugs should always be used as the first line of support to treat insomnia, not least because some of them can have serious side effects,” said Cipriani. “However, our research shows that some of these drugs can also be effective, and should be used in clinical practice, when appropriate. For example, where treatments such as improved sleep hygiene and Cognitive Behavioural Therapy have not worked, or where a patient wants to consider taking medication as part of their treatment.”

The new study was published in The Lancet.

Source: University of Oxford