Melatonin for Insomnia Tied to Increased Fracture Risk

By Reuters Staff

August 10, 2016

NEW YORK (Reuters Health) - Both melatonin and the "Z-drugs" zolpidem and zopiclone are independently associated with increased fracture risk, according to new findings.

"This study supports the growing evidence that Z-drugs are not safer than benzodiazepines with respect to the risk of fracture," Dr. Martin Frisher of Keele University in Staffordshire, U.K., and colleagues write in Age and Ageing, online July 26.

"Given the caution now attached to the prescribing of hypnotic drugs, this study may indicate that similar considerations should be attached to melatonin," they add.

Currently, melatonin is licensed in the U.K. for treating insomnia in patients 55 and older for up to 13 weeks. Use is on the rise, with 491,000 melatonin prescriptions written in England in 2014 compared to 262,000 in 2011, the researchers note.

This is likely due to concerns about the safety of Z-drugs and sedative hypnotics, they add, such as an increased risk of falls and fractures. While melatonin does not seem to have motor side effects, the researchers write, there is little information about the safety of the medication as compared to other insomnia treatments.

To investigate, the researchers looked at The Health Improvement Network data from 309 U.K. general practices for 2008-2013. Their analysis included patients 45 and older to reflect "real-life" use of melatonin.

The cohorts included 1,377 patients prescribed melatonin, 880 who were prescribed hypnotic benzodiazepines at least twice, 1,148 prescribed a Z-drug at least twice, and 2,752 controls matched by age, gender and practice who had not been exposed to the drugs. Follow-up lasted an average of 2.6 years.

Crude rates of the study's primary outcome, any fracture after study entry, were 6.0% with melatonin, 5.8% with hypnotic benzodiazepines, 5.9% for Z-drugs and 3.2% for controls.

After the researchers adjusted for 26 covariates, hazard ratios were 1.44 for melatonin (p=0.04), 1.26 for benzodiazepines (0.29), and 1.52 for Z-drugs (0.03). However, risk was only increased for melatonin when patients had received at least three prescriptions.

"As this study only shows an increased risk for the large diagnostic category of 'fracture,' further work could explore if the study drugs are associated with particular types of fracture that occur as a result of falling (e.g. hip fractures), which in turn may be caused by specific risk factors such as drowsiness," Dr. Frisher and his team write.

"In conclusion, prescriptions for melatonin and Z-drugs were associated with significantly increased risk of fracture over a two year period after adjusting for a range of potential confounders," they write. "The study design has a number of strengths which suggest that these findings are robust but we also note important limitations."


Age Ageing 2016.