New Head Injury Data Reinforce Restricted Antipsychotic Use in Dementia

Megan Brooks

January 16, 2020

Antipsychotic medications raise the risk of head injury and traumatic brain injury (TBI) in people with Alzheimer's disease (AD), new research shows.

These new data support long-standing evidence-based clinical guidance to limit the use of antipsychotics in dementia patients to those with the most severe neuropsychiatric symptoms and for as short a time as possible.

"Previous studies have shown an increased risk of falls and other fall-related injuries such as hip fractures. Ours is the first study investigating the association of antipsychotics to risks of head injuries and traumatic brain injuries," Vesa Tapiainen, MD, of the University of Eastern Finland in Kuopio, told Medscape Medical News.

"Antipsychotics are commonly used to treat neuropsychiatric symptoms of AD. However, antipsychotics use should be restricted to the most severe neuropsychiatric symptoms like severe aggression, agitation, or psychosis and for as short a period of time as possible according to the clinical care guidelines," Tapiainen added.

The study was published online January 7 in the Journal of the American Geriatrics Society.

Quetiapine Users Particularly Vulnerable

Antipsychotics have been linked to a range of adverse events in older adults with and without dementia, including an increased risk of death.

Using data from the Finnish nationwide Medication Use and Alzheimer's Disease (MEDALZ) cohort of Finnish community-dwelling adults with AD, the investigators matched 21,795 individuals who started taking an antipsychotic medication with 21,795 who did not. 

The mean age of the study population at baseline was 81.7 years, and two thirds were women. The most commonly initiated antipsychotics were risperidone (62% of users) and quetiapine (30%).

Compared with nonusers, antipsychotic users were more apt to be also taking a benzodiazepine, antidepressant, and opioid medication.

In multivariable-adjusted analyses, antipsychotic use was associated with a 29% higher risk of head injury (adjusted hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.14 - 1.47). The head injury event rate per 100 person-years was 1.65 in antipsychotic users vs 1.26 in nonusers. 

Antipsychotic use was also associated with a 22% higher risk of TBI (adjusted HR, 1.23; 95% CI, 1.03 - 1.46), with 0.90 events per 100 person-years in users compared with 0.72 per 100 person-years in nonusers.

Risks were highest at the beginning of antipsychotic use.

"Desperate" Need for Alternatives

When comparing antipsychotic medications, quetiapine users had a 60% higher risk of TBI compared with risperidone users.This may be explained by the different adverse effect profile of the two agents: quetiapine is considered to be more sedative, whereas risperidone more often causes extrapyramidal symptoms.

In addition, quetiapine may increase orthostatic hypotension more than risperidone. The researchers caution, however, that potential differences between the drugs should be confirmed in further studies.

"Following care guidelines and by carefully considering benefits and risks of adverse effects and events could possibly lower risks of head injuries," said Tapiainen.

"According to the clinical care guidelines, in treating the cause of neuropsychiatric symptoms, such as pain, nonpharmacological treatments should be first-line treatments in managing neuropsychiatric symptoms among persons with Alzheimer's disease," he added.  

Commenting on the findings for Medscape Medical News, Ramon Diaz-Arrastia, MD, PhD, said the novelty in the results is "pretty marginal."

"Antipsychotic drug use in AD has been associated with increased falls and increased mortality from many causes. It is pretty clear that these are not good drugs to use in the elderly, and those with AD in particular," said Diaz-Arrastia, associate director for clinical research at the Center for Neurodegeneration and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

"Despite that, they are still used, since behavioral problems can be a big issue in demented older people," he noted. "We are in desperate need for alternate treatments."

The study had no commercial funding. Tapiainen and Diaz-Arrastia have disclosed no relevant financial relationships .

J Am Geriatr Soc. Published online January 7, 2020. Abstract

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