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Use of antipsychotics in patients with dementia has long under fire because of limited efficacy and occurrence of serious adverse effects, such as an increase in stroke and mortality. They may also cause sedation, extrapyramidal signs, and some may produce orthostatic hypotension. The latter may all contribute to falls and fractures. Some also predispose to development of metabolic syndrome or glucose intolerance. And some may be associated with severe reactions, such as the neuroleptic malignant syndrome.
Several of our columns have addressed attempts by CMS to reduce use of antipsychotic agents in nursing home patients with dementia (see our February 3, 2015 Patient Safety Tip of the Week CMS Hopes to Reduce Antipsychotics in Dementia and our May 2018 What's New in the Patient Safety World column Antipsychotic Use in Nursing Homes: Progress or Not?).
In 2005, the US Food and Drug Administration (FDA) issued a boxed warning for the use of AAPs in elderly patients. But no one really considered the possibility that unintended consequences might pop up once those drugs were discontinued. In a new study, Rubino et al. (Rubino 2020) found that prescription of atypical antipsychotics to patients age 65 and older who had a diagnosis of dementia did decrease significantly following addition of the FDA black box warning. As hoped, falls and fractures and cerebrovascular events also decreased. But they found that opioid use, antiepileptic use, cardiovascular events, and 2-year mortality risk increased. Health-related quality of life remained relatively unchanged.
Our first thought was that this period likely coincided with a rise in opioid use in the general population. However, Rubino et al. note that a study in Medicare beneficiaries found that opioid use remained stable between 2007 and 2017, suggesting that the increase observed may be specific to the population of elderly patients with dementia. The reasons for the increased rate of opioid use are unclear because the evidence base for their use in treatment of dementia-related agitation is limited. They note it is possible that opioids could have been used to treat pain in some cases because pain is increasingly recognized as a contributor to agitation in patients with dementia. The article did not provide a breakdown by specific antiepileptic drug. It would have been helpful to know whether the increased use was primarily for gabapentinoids, which might have been being used adjuncts for pain management rather than as antiepileptics.
So, should we go back to prescribing antipsychotics for agitation in patients with demenia? Of course not. But the Rubino study does tell us we must remain vigilant for unintended consequences any time we implement a solution designed to improve one aspect of care.
Several other recently published studies deal with antipsychotics in patients with dementia.
One study from Finland (Tapiainen 2020) found that antipsychotic use may increase the risk of head injuries and traumatic brain injuries in persons with Alzheimers Disease.
Another study looked at the prevalence of psychotropic medicine (antipsychotic, benzodiazepine, or antidepressant medicines) dispensing before and after older people enter residential care in Australia (Harrison 2020). They found that dispensing of psychotropic medicines was high before they enter residential care but increased markedly soon after entry into care. The authors stress that non‐pharmacological behavioral management strategies are important for limiting the prescribing of psychotropic medicines for older people in the community or in residential care.
Another article from Australia (Byrne 2020) notes we tend to blame prescribing of psychotropic medication for people living in residential aged care facilities (RACFs) on prescribers. But, the author notes that many RACFs are poorly equipped for managing cognitively impaired older people with challenging behaviors, particularly ambulant residents with dementia. Byrne notes that not all RACFs have adequate circulation space for reducing the likelihood of aggressive incidents, or accessible outside areas for regular physical exercise. Some RACFs have insufficient natural light for maintaining normal sleep/wake cycles, and many do not have enough staff trained in managing the behavioral and psychological symptoms of their residents. In some locations, public sector mental health services can assist with the assessment and management of RACF residents with mental illness or challenging behavior, but these services are often under‐resourced and unable to respond quickly. We suspect all these circumstances are also common in long-term care facilities in the US.
So, how do we reduce inappropriate prescribing of antipsychotics to patients with dementia? Obviously, provision of non-pharmacologic means of behavioral modification is the best approach.
Though the 2005 FDA Black Box Warning noted above may have reduced prescribing of atypical antipsychotics, attempts to accomplish the goal by education have not met with success. A study just published (Tadrous 2020) evaluated the effectiveness of academic detailing in nursing homes in Ontario, Canada targeting appropriate prescribing of antipsychotics. Academic detailing was delivered by health professionals (eg, nurses or pharmacists) through meetings with administrators, physicians, pharmacists, nurses, and support workers, presentations, group visits (with 2-6 clinicians), and 1-on-1 visits (traditional academic detailing visits). Those doing the academic detailing had direct and ongoing contact with the nursing homes from the time of launch. Unfortunately, the intervention did not further reduce antipsychotic prescribing in nursing homes beyond system-level secular trends occurring alongside usual care. Interestingly, the intervention group had significant reductions in pain and depression compared to the control group.
And then there are the serendipitous findings. We like to retell one of
our favorite anecdotal stories about unintended consequences. This one was a
positive unintended consequence. One month a skilled nursing facility (SNF)
reported a dramatic decline in the number of patient falls. Surely, this must
have been a reporting error. No, it wasnt. It
turned out that the SNFs contract with a psychiatrist had expired so there
were no renewals of antipsychotics, antidepressants, and other psychotropic
drugs that had been ordered for patients with dementia. Of course, that is not
a randomized, controlled trial but the implications of the observation are
dramatic.
No, we dont actually recommend you cut your ties with your
behavioral health consultants! But we think that using clinical decision
support (CDS) tools can provide reminders to assess the need or continuing need
for antipsychotics in your long-term care patients. If you decide that such use
is not appropriate or no longer appropriate, consider deprescribing. The
deprescribing.org website has a nice algorithm
for deprescribing antipsychotics and links to a guideline for deprescribing
antipsychotics (Bjerre 2018).
Some of our past columns on Beers List and Inappropriate Prescribing in the Elderly:
Some of our past columns on deprescribing:
References:
Rubino A, Sanon M, Ganz ML, et al. Association of the US Food and Drug Administration Antipsychotic Drug Boxed Warning With Medication Use and Health Outcomes in Elderly Patients With Dementia. JAMA Netw Open 2020; 3(4): e203630
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765053
Tapiainen V, Lavikainen P. Koponen M, et al. The Risk of Head Injuries Associated With Antipsychotic Use Among Persons With Alzheimer's disease. J Am Geriatr Soc 2020; First published January 7, 2020
https://onlinelibrary.wiley.com/action/showCitFormats?doi=10.1111%2Fjgs.16275
Harrison SL, Sluggett JK, Lang C, et al. The dispensing of psychotropic medicines to older people before and after they enter residential aged care. Med J Aust 2020; 212 (7): 309-313 Published online: 2 March 2020
Byrne GJ. Prescribing psychotropic medications in residential aged care facilities. Med J Aust 2020; 212 (7): Published online: 20 April 2020
deprescribing.org
Antipsychotic (AP) Deprescribing Algorithm. deprescribing.org
https://deprescribing.org/wp-content/uploads/2018/08/AP-deprescribing-algorithm-2018-English.pdf
Bjerre LM, Farrell B, Hogel
M, et al. Deprescribing antipsychotics for behavioural
and psychological symptoms of dementia and insomnia. Evidence-based clinical
practice guideline. Canadian Family Physician 2018, 64(1): 17-27
https://www.cfp.ca/content/64/1/17?etoc
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