Some antidepressants and incontinence drugs linked to dementia

Thursday April 26 2018

"Some antidepressants and bladder medicines could be linked to dementia," BBC News reports. Researchers reviewed GP records of more than 300,000 people to look for links between dementia and drugs that belong to a group of medicines known as anticholinergic drugs.

These drugs block a chemical called acetylcholine, which can affect a wide range of the body's organs. Because of this anticholinergics are used to treat many, often unrelated, conditions such as depression, urinary incontinence and Parkinson's disease.

It has been known for some time that anticholinergics can cause problems with thinking; especially in older people. But it's been unclear whether they also raise the risk of dementia in the long term.

This study found that anticholinergic drugs were linked with about a 10% increase in the chances of dementia. However, not all anticholinergic drugs showed this effect. People who'd taken anticholinergic antidepressants, drugs for Parkinson's disease, and drugs used for urinary incontinence were more likely to have developed dementia. Those who'd taken anticholinergic drugs for cardiovascular or gastrointestinal conditions did not have an increased risk.

This type of study cannot show that anticholinergic drugs cause dementia.

It is also important to stress that the researchers think the risk to individuals is small. They said doctors should exercise caution in prescribing drugs with these effects, and think about possible long-term consequences, as well as short-term side effects.

Don't stop taking any prescribed medication before speaking to your GP first.

Where did the story come from?

The study was done by researchers from the University of East Anglia, Aston University, the University of Aberdeen, Newcastle University and the University of Cambridge in the UK, the Royal College of Surgeons in Ireland, and Purdue University and Indiana University in the US. It was funded by the Alzheimer's Society and published in the peer-reviewed British Medical Journal (BMJ) and is free to read online.

The reporting of the study in the UK media was mostly accurate, although some headlines may have misled readers to think that all anticholinergic drugs carry a risk; such as The Times headline: "Everyday drugs linked to dementia". Some of the reporting failed to make it clear that the study does not prove that anticholinergic drugs cause dementia.

Much of the coverage seems to have come from a press conference given by the researchers, who apparently estimated that 200,000 people in the UK might have dementia caused by anticholinergics. We can't assess that claim, as it and the data used to make it are not included in the study.

What kind of research was this?

This was a case-control study using a large GP database of UK patients records. Case-control studies are useful for assessing the differences in exposure to risk factors (such as anticholinergic drugs) between people who have a condition (dementia in this case) and those who do not. However, they can't prove that the risk factor causes the condition.

What did the research involve?

Researchers identified 40,770 people diagnosed with dementia, who had good quality data on their prescriptions for at least 6 years before their diagnosis. They matched each of them to up to 7 people without dementia, who were the same age and sex and came from a similar area as them, giving a total of 283,993 people in the control group.

The researchers looked at the medicines they had taken in the 4 to 20 years before their dementia diagnosis (or for the controls, the date of the diagnosis of the person they'd been matched to).

They analysed the data to look at:

  • types of anticholinergics
  • drugs with different levels of anticholinergic activity
  • how long people had taken the drugs for, and at which doses

After adjusting their figures for potentially confounding factors, the researchers looked to see whether any types of anticholinergic drugs were linked to a higher risk of getting dementia.

Confounding factors included:

  • age
  • region
  • falls
  • doctor consultations
  • prescriptions for certain other non-cholinergic drugs
  • body mass index
  • smoking
  • harmful alcohol use
  • medical conditions (including depression and length of depression)

The drugs were assessed using an evidence-based classification system known as the Anticholinergic Cognitive Burden (ACB) scale, which scores drugs on a 1 to 3 scale based on how likely they are likely to disrupt thinking (3 being the highest).

They also looked separately at anticholinergic drugs prescribed for:

  • pain relief
  • depression
  • psychosis
  • cardiovascular conditions
  • gastrointestinal conditions
  • Parkinson's disease
  • respiratory disease
  • bladder conditions

What were the basic results?

Overall, people who had dementia were more likely to have been prescribed an anticholinergic drug:

  • 35% of people with dementia and 30% of people without had been prescribed at least 1 class 3 anticholinergic drug
  • people with dementia were 11% more likely to have taken a class 3 anticholinergic drug (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 1.08 to 1.14)

This risk does not apply to all types of anticholinergic drugs, however. Drugs for different conditions are linked to different levels of risk. Anticholinergic antidepressants (amitriptyline), drugs for bladder problems (oxybutynin and tolterodine), and drugs for Parkinson's disease (procyclidine, orphenadrine, trihexyphenidyl) showed evidence of increased risk of dementia.

For class 3 anticholinergics:

  • antidepressants had a 13% increased risk (aOR 1.13, 95% CI 1.10 to 1.16)
  • antiparkinson drugs had a 45% increased risk (aOR 1.45, 95% CI 1.25 to 1.68)
  • bladder drugs had a 23% increased risk (aOR 1.23, 95% CI 1.18 to 1.28)

It helps to put the risk in context. Around 10 in 100 people aged 65 to 70 will develop dementia over the next 15 years. If people had taken antidepressants 15 to 20 years beforehand, they would have an increased risk of 19% above the baseline risk (aOR 1.19, 95% CI 1.10 to 1.29). This would mean that an additional 1 to 3 in 100 people would get dementia.

How did the researchers interpret the results?

The researchers said their results showed "robust associations between levels of anticholinergic antidepressants, antiparkinsons [drugs used to treat Parkinson's] and urologicals [drugs used to treat bladder conditions], and the risk of a diagnosis of dementia up to 20 years after exposure".

They said "other anticholinergics appear not to be linked to the risk of dementia".

They added that doctors "should continue to be vigilant with respect to the use of anticholinergic drugs" and should "consider the risk of long-term cognitive effects" when thinking about whether the benefits of these drugs outweigh the possible harms.

Conclusion

The headlines to this story make for alarming reading, especially if you are taking a drug such as an antidepressant. While the study does raise concerns, it's important to remember the potential added risk to any individual is small, and that the risk is not proven.

The study was carefully conducted with a great deal of data. However, there are a few limitations to be aware of, which could affect the accuracy of the results:

  • dementia is under-diagnosed, and as many as half of people with dementia may not have a diagnosis recorded in their notes
  • over-the-counter drugs are not included in the GP database, so people in the study might have been taking anticholinergic drugs that were not recorded
  • as we don't know the causes of dementia, it's not possible to adjust the data to take account of all of them, and some unmeasured confounding factors may not have been included

If you are concerned about the risk of any drug you are taking, talk to your doctor. Not all drugs for bladder problems, depression or Parkinson's disease are anticholinergic, so you may not be affected at all. For example, the more commonly prescribed antidepressants citalopram, sertraline, fluoxetine would not be a class 3 anticholinergic drug and were not included in this analysis.

If you are taking an anticholinergic drug for one of these conditions, you could discuss whether the benefits outweigh the risks, and whether there is an alternative you could switch to. It's safer to carry on taking prescribed medicines until you’ve discussed it with your doctor – don't just stop taking them.

Analysis by Bazian
Edited by NHS Website