Changes in sleep patterns are very common in dementia. Once the disease advances these changes can develop into more severe sleep disturbances, with people having either problem falling asleep, waking up multiple times in the night or having increased daytime sleepiness.
Sleep medication is often prescribed by clinicians in those cases, however, recent evidence suggests that sleep medication can have unintended adverse effects in older people, including falls, bone fractures and even strokes.
What is the scientific evidence for the side effects of sleep medication in dementia? A recent study explored the evidence.
We often underestimate how important sleep is in our lives. On average we sleep nearly a quarter of our lives, which shows how important sleep is for our bodies as nature would not let us spend all this time sleeping if there was no function for it.
Sleep has various functions in our bodies but one key function is to allow the body to do a ‘tidy-up’ and repair. Significant usage results in a lot of wear & tear as well as waste. The same is true for our body – and our brain – which uses part of our sleep to repair our cells or remove waste products from cells.
Such repair and tidying of our brain during sleep are particularly important when we have dementia. Several research studies have shown that for example excess Amyloid – a key protein involved in Alzheimer’s disease – is more efficiently removed during sleep. Good sleep is therefore important to reduce our risk for dementia and also might help the progression of the disease when we have it.
However, sleep becomes increasingly disrupted when dementia advances. The exact mechanisms of how the disease processes in dementia disrupt sleep are still being investigated. Most people with dementia report sleep changes, including having more disrupted nighttime sleep or increased daytime sleepiness.
In the moderate and severe stages of dementia, these sleep changes can become more disruptive and result in people being awake for long periods during the night, with some even losing completely the day-night rhythm.
This disruptive sleep can be very upsetting for the person with dementia as it can worsen symptoms and it also affects their carers and families who often are faced with a confused person being up in the middle of the night, who cannot go back to sleep.
In such situations, clinicians often prescribe sleep medication for people with dementia to alleviate these sleep disruptions. However, sleep medications are not an easy solution, as they appear to be, as they can have unintended adverse effects on people with dementia.
In the past, the ‘go-to-choice’ for sleep medication for people with dementia were benzodiazepines – a simple way to recognise benzodiazepine medication is that most of their names end with the suffix ‘-am’, like Diazepam, Alprazolam or Lorazepam.
However, over the years it became apparent that benzodiazepines can have some severe side/adverse effects in people with dementia, such as increased cognitive impairment but also increased falls. On top of that, there was increasing recognition that long-term use of benzodiazepines leads to a dependency/addiction to the medication, making doctors more reluctant to prescribes this class of sleep medication for long-term diseases, such as dementia.
Fortunately, a new class of sleep medication was developed and came to market a few years ago. This new class of sleep medication is commonly called ‘Z-drugs’ – the names of most of this medication class start with the letter ‘Z’, such as Zopiclone, Zaleplon and Zolpidem.
What are Z-drugs?
Z-drugs are ‘non-benzodiazepine gamma-aminobutyric acid agonists’, which – admittedly – is quite a mouthful, so let’s unpack it a bit.
‘Non-benzodiazepine’ means these drugs are not benzodiazepines (Duh!), but they have similar effects to benzodiazepines. ‘Gamma-aminobutyric acid’ is often referred to in its acronym form – GABA. GABA is a common molecule in the brain used for transmitting signals between nerve cells. Molecules, such as GABA, which allow transmitting signals between brain cells are referred to as neurotransmitters. The final word ‘agonist’ means that it works against something. In essence, the Z-drugs are blocking or reducing the function of the neurotransmitter GABA in the brain, which makes us more drowsy or sleepy.
Overall, the Z-drugs are therefore a clever solution to make people more sleepy who have problems falling or staying asleep by changing the function of the GABA neurotransmitter. Z-drugs were also thought not to have such significant side effects as benzodiazepines, as they are deemed less addictive than benzodiazepines. Z-drugs emerged, therefore, as an alternative treatment solution to benzodiazepines for sleep disruptions in people with dementia.
However, and it is a big “however”, recent evidence suggested that Z-drugs still have some significant side/adverse effects in older people. In particular, research suggested that taking Z-drugs increased the numbers of falls older people have. Such falls can be potentially very dangerous for older people as they can lead to injuries, such as bone fractures, requiring hospitalisation and a potential move to residential care facilities due to the resulting limited mobility after a bone fracture.
The reason why falls are so strongly associated with sleep medication – including Z-drugs – is that the drugs not only make us more drowsy but they also affect how our muscles work. GABA is also a key molecule for relaying nerve signals to our muscles, and hence reducing/blocking GABA also affects our muscles. Specifically, Z-drugs and benzodiazepines, affect our muscle tone by ‘relaxing our muscles’ – they are often referred to as muscle relaxants.
This means that Z-drugs cannot only cause falls because we feel drowsy/sleepy but also because Z-drugs ‘relax our muscles’, which affects our muscle control making it more likely that we fall, as our legs ‘simply give away’.
The evidence that Z-drugs have these adverse effects in healthy older people are well established but doe they have the same adverse effects for people with dementia?
A recent study* investigated exactly this issue but analysing data of 27,090 people with dementia. The researchers compared people who had diagnosed sleep disturbances and were prescribed Z-drugs to those that had diagnosed sleep disturbances but did not take any medication. Finally, they compared the groups to other people with dementia who were prescribed benzodiazepine for their diagnosed sleep disruptions.
The researchers were interested to find out if people on Z-drugs had a higher risk of bone fractures, falls, bacterial infections, strokes or even death. All factors which were previously associated with Z-drug adverse effects in older people.
The results of their research showed that people with dementia on Z-drug medication were indeed at a high risk of bone fractures, in particular hip fractures, which are the most common fractures in older people leading to hospitalisation. In addition, people with dementia on Z-drugs were at higher risk for falls and strokes. But their risk for bacterial infections or death was not increased compared to the people with sleep disturbances but not on Z-drugs.
However, before you rush off to stop taking your Z-drug medication, there was another important finding in the study, in that the dosage of the medication made a big difference to the risk for adverse effects. The highest risk was for people on a high dosage of Z-drugs but there was minimal or inconsistent adverse risks for people on Zopiclone, the most commonly prescribed Z-drug, with a dosage of less than 3.75 mg daily.
Interestingly, the adverse side effects in people with dementia on a high dosage of Z-drugs were of similar magnitude as people who were taking benzodiazepines. This makes clear that Z-drugs might not be the panacea they were proclaimed to be as they can have – at higher dosage – similar adverse effects to benzodiazepines, albeit Z-drugs are less addictive in the long-term.
In summary, higher dosage Z-drugs are increasing the risk for bone fractures, falls and strokes in people with dementia, similar to people on benzodiazepines. These increased adverse effects were not seen for people with dementia on lower Z-drugs dosage – although a smaller risk remained.
The authors conclude that the dosage of Z-drugs should be closely monitored and discussed with the treating doctor. As always, please do not change or stop your medication before consulting with your doctor, as this might lead to different side/adverse effects.
Something else to consider is to use non-pharmacological interventions for alleviating sleep disturbances, such as behavioural or light therapies. There is promising research that such more holistic approaches might be helpful for alleviating these symptoms as well.
Something to sleep over…
*Richardson, K., Loke, Y.K., Fox, C. et al. Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study. BMC Med 18, 351 (2020). https://doi.org/10.1186/s12916-020-01821-5