'Z' Drugs Significantly Boost Fracture Risk in Dementia Patients

Pauline Anderson

July 25, 2018

CHICAGO — Prescribing hypnotics such as zolpidem (multiple brands), zopiclon (Lunesta, Sunovion), or zaleplon (Sonata, Pfizer) to treat sleep problems in dementia patients significantly increases fracture risk in this vulnerable population, new research shows.

These so-called Z drugs were found to increase overall fracture risk by 40% and the risk for hip fracture by 59%.

"We are poisoning our patients" by overmedicating them, said study author Ian Maidment, PhD, senior lecturer in clinical pharmacy, Aston University, Birmingham, United Kingdom. "We need to find alternatives to drugs for treating sleep problems in people with dementia."

The study was presented here at the Alzheimer's Association International Conference (AAIC) 2018.

"Shocking" Statistic

About 60% of people with dementia experience sleep disturbances, which can include insomnia and excessive daytime sleeping, Maidment said at a press briefing here.

Z drugs work in a manner similar to that of benzodiazepines and in many cases have replaced these drugs. In 2015, 3.8 million Americans were taking zolpidem, said Maidment.

About two thirds (64%) of older people in the United States are receiving high doses of zolpiden, a figure Maidment finds "shocking."

Despite these drugs being widely used, there is concern that they may cause falls and fractures. However, little information is available on the safety of these hypnotics in patients with dementia, said Maidment.

To study this issue, investigators used the Clinical Practice Research Datalink, the most widely used clinical database in the United Kingdom. It houses primary care records and hospital data related to 13 million patients.

From this database, the researchers included patients who had been diagnosed with dementia and who had experienced a sleep disturbance. These patients were categorized into those who had received a Z-drug prescription (n = 2952) and those who had not (n = 1651). Maidment said these numbers illustrate how commonly used these drugs are in this patient population.

After a follow-up of up about 2 years, the analysis showed that patients taking a Z drug had a 40% increased risk for a fracture compared to those not taking this type of sleep drug.

"If you have dementia, your risk of having a fracture is 7% per year; if you're taking a Z drug, that increases to 10%," said Maidment. "So we are looking at one additional fracture for 36 people living with dementia taking one of of these drugs."

For hip fractures, the increased risk "is even starker," at 59%, said Maidment. "If you have dementia, your risk of a hip fracture is 3%, but if you take a Z drug, your risk increases to 5%. That's one additional fracture per 54 people."

Increased Vulnerability

There was no increase in reported falls among the group receiving a Z drug. However, Maidment believes this reflects a problem involving coding, in which general practitioners record the fracture but not the fall that caused it.

He added that Z drugs sedate patients, which makes them more vulnerable to falls.

The researchers also assessed drug dose and duration using defined daily doses (DDDs). There was no risk with DDDs of less than 28, but the risk increased at higher doses and longer duration.

For DDDs of 28 to 41, the risk nearly doubled. For example, Maidment said, the risk for a hip fracture in the following year increases from 7% to 14%, and the risk for a hip fracture increases from 3% to 6%.

The study provides "a clear signal" that these drugs affect hip fracture risk, Maidment told Medscape Medical News. He added that there is "good evidence" that hip fractures are linked to mortality.

Asked what he would prescribe to patients with dementia who experience problems sleeping, Maidment said "nothing." He noted that no drug is "perfectly safe."

He emphasized the need to consider nonpharmaceutical approaches for sleep problems, including physical activity, avoidance of caffeine, and use of person-centered care.

"We need to find an alternative to drugs," he said. "I'm a pharmacist and have worked with drugs for 30 years, but I think we need to move away from that."

Maidment said he's concerned that patients are being started on these drugs and then are not being properly managed.

Stopping Z drugs might result in an increase in patients wandering and perhaps an increase in agitation, he said.

Not for Seniors

Press briefing moderator Julie A. Schneider, MD, professor of pathology and neurologic sciences, Rush University Medical Center and Rush Alzheimer's Disease Center, Chicago, Illinois, who is on the Alzheimer's Association Medical and Scientific Affairs Advisory Council, noted that expert groups recommend changing the environment and using nonmedical therapies for sleep problems before turning to medications.

Asked for his views of this research, James Hendrix, PhD, director, Global Science Initiatives, Alzheimer's Association, said it reinforces the message that Z drugs cause sedation, particularly in older people who may have problems with balance, and can increase the risk for fractures.

Hendrix agreed that "physicians should look for alternatives" that have fewer side effects. However, he recognized that "not everyone will have access to those alternatives."

Because sleep disturbances are "very common and a serious effect" of Alzheimer's disease and dementia, "we need more research to find better alternatives for older people."

He noted that these drugs were developed for adults in midlife "and not necessarily for seniors."

The investigators have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2018. Abstract 23209, presented July 24, 2018.

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