Anticholinergics’ link to dementia calls for vigilance in elderly

 

Antidepressant, urologic, and antiparkinson drugs with definite anticholinergic activity were associated with an increased risk of dementia as long as 20 years after exposure in a large observational study published in The BMJ.

Kathryn Richardson, PhD, of the University of East Anglia, Norwich, England, and her colleagues said that while the associations were “moderate” given the high incidence of dementia observed in the study, they nevertheless reflected an “appreciable risk” for patients.

MarkRyanDesigns/getty images

“Clinicians should continue to be vigilant with respect to the use of anticholinergic drugs, and should consider the risk of long-term cognitive effects, as well as short-term effects, associated with specific drug classes when performing their risk-benefit analysis,” the research team advised.

According to a linked editorial by Shelly L. Gray, PharmD, of the University of Washington, Seattle, and Joseph T. Hanlon, PharmD, of the University of Pittsburgh, the findings suggest that anticholinergics in general should be avoided in older adults (BMJ. 2018;361:k1722. doi: 10.1136/bmj.k1722).

“Specifically, for most highly anticholinergic drugs, nonpharmacological and pharmacological alternatives are available and should be considered,” they said.

The nested case-control study involved 40,770 patients from the United Kingdom’s Clinical Practice Research Database who were aged 65-99 years and diagnosed with dementia between April 2006 and July 2015. The research team matched the patients to 283,933 similar controls without dementia.

They scored drugs according to their anticholinergic activity using the Anticholinergic Cognitive Burden (ACB) scale: A score of 1 was classified as possibly anticholinergic, while a score of 2 or 3 was classified as having “definite” anticholinergic activity. Daily doses of each drug were then compared for both cases and controls over an exposure period of 4-20 years before a diagnosis of dementia.

 

Overall, 14,453 cases (35%) and 86,403 controls (30%) were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. People prescribed greater dosage quantities over time of probable (ACB category 2) and definite (ACB category 3) anticholinergics had a higher risk of dementia, the researchers reported.

For example, anticholinergic use consistent with the highest dose category (more than 1,460 defined daily doses) was associated with an adjusted odds ratio for dementia of 1.57 (95% confidence interval, 1.18-2.09) for probable and 1.31 (95% CI, 1.22-1.41) for definite anticholinergics.

However, no increased risk was found for anticholinergics used to treat gastrointestinal, cardiovascular, or respiratory conditions. The research team also found no evidence for a cumulative harm of drugs considered “possibly” anticholinergic.

“A typical patient aged 65-70 might normally expect a period incidence of dementia of around 10% over the next 15 years, so this odds ratio would be consistent with an absolute risk increase of 2% (1% to 3%) over that period, corresponding to a number needed to harm of 50 (33 to 100),” they wrote.

 

They suggested that their findings could be explained by the drugs being markers of prodromal symptoms or dementia risk factors. The class effect observed might also reflect differences in the way anticholinergics crossed the blood-brain barrier.

The Alzheimer’s Society supported the research. Several of the authors reported receiving personal fees from Astellas. One author declared personal fees from Thame Pharmaceuticals.

SOURCE: Richardson K et al. BMJ. 2018;360:k1315. doi: 10.1136/bmj.k1315.

 

Antidepressant, urologic, and antiparkinson drugs with definite anticholinergic activity were associated with an increased risk of dementia as long as 20 years after exposure in a large observational study published in The BMJ.

Kathryn Richardson, PhD, of the University of East Anglia, Norwich, England, and her colleagues said that while the associations were “moderate” given the high incidence of dementia observed in the study, they nevertheless reflected an “appreciable risk” for patients.

MarkRyanDesigns/getty images

“Clinicians should continue to be vigilant with respect to the use of anticholinergic drugs, and should consider the risk of long-term cognitive effects, as well as short-term effects, associated with specific drug classes when performing their risk-benefit analysis,” the research team advised.

According to a linked editorial by Shelly L. Gray, PharmD, of the University of Washington, Seattle, and Joseph T. Hanlon, PharmD, of the University of Pittsburgh, the findings suggest that anticholinergics in general should be avoided in older adults (BMJ. 2018;361:k1722. doi: 10.1136/bmj.k1722).

“Specifically, for most highly anticholinergic drugs, nonpharmacological and pharmacological alternatives are available and should be considered,” they said.

The nested case-control study involved 40,770 patients from the United Kingdom’s Clinical Practice Research Database who were aged 65-99 years and diagnosed with dementia between April 2006 and July 2015. The research team matched the patients to 283,933 similar controls without dementia.

They scored drugs according to their anticholinergic activity using the Anticholinergic Cognitive Burden (ACB) scale: A score of 1 was classified as possibly anticholinergic, while a score of 2 or 3 was classified as having “definite” anticholinergic activity. Daily doses of each drug were then compared for both cases and controls over an exposure period of 4-20 years before a diagnosis of dementia.

 

Overall, 14,453 cases (35%) and 86,403 controls (30%) were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. People prescribed greater dosage quantities over time of probable (ACB category 2) and definite (ACB category 3) anticholinergics had a higher risk of dementia, the researchers reported.

For example, anticholinergic use consistent with the highest dose category (more than 1,460 defined daily doses) was associated with an adjusted odds ratio for dementia of 1.57 (95% confidence interval, 1.18-2.09) for probable and 1.31 (95% CI, 1.22-1.41) for definite anticholinergics.

However, no increased risk was found for anticholinergics used to treat gastrointestinal, cardiovascular, or respiratory conditions. The research team also found no evidence for a cumulative harm of drugs considered “possibly” anticholinergic.

“A typical patient aged 65-70 might normally expect a period incidence of dementia of around 10% over the next 15 years, so this odds ratio would be consistent with an absolute risk increase of 2% (1% to 3%) over that period, corresponding to a number needed to harm of 50 (33 to 100),” they wrote.

 

They suggested that their findings could be explained by the drugs being markers of prodromal symptoms or dementia risk factors. The class effect observed might also reflect differences in the way anticholinergics crossed the blood-brain barrier.

The Alzheimer’s Society supported the research. Several of the authors reported receiving personal fees from Astellas. One author declared personal fees from Thame Pharmaceuticals.

SOURCE: Richardson K et al. BMJ. 2018;360:k1315. doi: 10.1136/bmj.k1315.

 

Antidepressant, urologic, and antiparkinson drugs with definite anticholinergic activity were associated with an increased risk of dementia as long as 20 years after exposure in a large observational study published in The BMJ.

Kathryn Richardson, PhD, of the University of East Anglia, Norwich, England, and her colleagues said that while the associations were “moderate” given the high incidence of dementia observed in the study, they nevertheless reflected an “appreciable risk” for patients.

MarkRyanDesigns/getty images

“Clinicians should continue to be vigilant with respect to the use of anticholinergic drugs, and should consider the risk of long-term cognitive effects, as well as short-term effects, associated with specific drug classes when performing their risk-benefit analysis,” the research team advised.

According to a linked editorial by Shelly L. Gray, PharmD, of the University of Washington, Seattle, and Joseph T. Hanlon, PharmD, of the University of Pittsburgh, the findings suggest that anticholinergics in general should be avoided in older adults (BMJ. 2018;361:k1722. doi: 10.1136/bmj.k1722).

“Specifically, for most highly anticholinergic drugs, nonpharmacological and pharmacological alternatives are available and should be considered,” they said.

The nested case-control study involved 40,770 patients from the United Kingdom’s Clinical Practice Research Database who were aged 65-99 years and diagnosed with dementia between April 2006 and July 2015. The research team matched the patients to 283,933 similar controls without dementia.

They scored drugs according to their anticholinergic activity using the Anticholinergic Cognitive Burden (ACB) scale: A score of 1 was classified as possibly anticholinergic, while a score of 2 or 3 was classified as having “definite” anticholinergic activity. Daily doses of each drug were then compared for both cases and controls over an exposure period of 4-20 years before a diagnosis of dementia.

 

Overall, 14,453 cases (35%) and 86,403 controls (30%) were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. People prescribed greater dosage quantities over time of probable (ACB category 2) and definite (ACB category 3) anticholinergics had a higher risk of dementia, the researchers reported.

For example, anticholinergic use consistent with the highest dose category (more than 1,460 defined daily doses) was associated with an adjusted odds ratio for dementia of 1.57 (95% confidence interval, 1.18-2.09) for probable and 1.31 (95% CI, 1.22-1.41) for definite anticholinergics.

However, no increased risk was found for anticholinergics used to treat gastrointestinal, cardiovascular, or respiratory conditions. The research team also found no evidence for a cumulative harm of drugs considered “possibly” anticholinergic.

“A typical patient aged 65-70 might normally expect a period incidence of dementia of around 10% over the next 15 years, so this odds ratio would be consistent with an absolute risk increase of 2% (1% to 3%) over that period, corresponding to a number needed to harm of 50 (33 to 100),” they wrote.

 

They suggested that their findings could be explained by the drugs being markers of prodromal symptoms or dementia risk factors. The class effect observed might also reflect differences in the way anticholinergics crossed the blood-brain barrier.

The Alzheimer’s Society supported the research. Several of the authors reported receiving personal fees from Astellas. One author declared personal fees from Thame Pharmaceuticals.

SOURCE: Richardson K et al. BMJ. 2018;360:k1315. doi: 10.1136/bmj.k1315.