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Determining the Most Beneficial Atypical Antipsychotic Treatment for Dementia Symptoms

June 06, 2019

By Julie Gould

ismaeel YunusaIsmaeel Yunusa, PharmD, of the School of Pharmacy at the Massachusetts College of Pharmacy and Health Sciences in Boston, recently spoke with Annals of Long-Term Care to discuss the results of his recent study published online in JAMA Network Open. According to the study, “the existence of a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of [behavioral and psychological symptoms of dementia] and confirms that a single most effective and safe treatment option does not exist.”

Dr Yunusa explains how the study findings correlate to the 2015 AGS Beers Criteria update and highlights knowledge gaps that still exist regarding which atypical antipsychotic is both safe and beneficial for patients with dementia.  

Please tell us a little about yourself and your research interests.  

I am a pharmacist, with interest in optimizing pharmacotherapy of geriatric patients, and I am also a pharmaceutical health outcomes researcher. My specific research interests include comparative effectiveness research, drug utilization studies, drug safety, pharmacoeconomics and outcomes research.  

How often are atypical antipsychotics prescribed to older adults with dementia? Are patients still commonly prescribed these drugs despite the boxed warning? 

According to a study, atypical antipsychotics are prescribed in 12-37% of older adults with behavioral and psychological symptoms of dementia. Although the use varies by provider and care setting, I would say it is still at a rate that calls for concern despite reduction over the years.  

Can you briefly highlight how your findings correlate to the 2015 AGS Beers Criteria update?

The 2015 AGS Beers Criteria update recommends that antipsychotics should be avoided in older adults because they are associated with increased risk of cerebrovascular adverse events (CVAE), particularly stroke. Our study found that two atypical antipsychotics (risperidone and olanzapine) are associated with an over 3-4 fold increased risk of CVAE compared with placebo. Guidelines from the American Psychiatric Association also recommends avoiding risperidone and olanzapine in patients with risk of CVAE.

The Beers criteria also recommends that all antipsychotics should be avoided in persons with Parkinson’s disease except aripiprazole and quetiapine. These two drugs were ranked as the relatively safest among the 4 atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in terms of the risk of another movement disorder, extrapyramidal signs and symptoms.  

What are the major takeaways from your study? How can clinicians take the findings and implement them into practice?  

Sometimes, nonpharmacological strategies in form of behavioral therapies can be ineffective or impossible and patients with severe dementia may threaten to harm themselves or others, consistent with the guidelines, physicians might consider giving these patients atypical antipsychotics. In such cases, our study serves as a guide for physicians to personalize treatments by avoiding drugs that are associated with a particular risk given a patient’s medical history and current status. The cluster ranking plot where we compared effectiveness and safety in a single plot can severe as a guide in such a situation.  

Our study also calls for countries (UK, Canada Australia, and New Zealand) in which only risperidone is approved to review their decision as aripiprazole and quetiapine can be better candidates given their positions in the cluster ranking plot.  

Following the results of your study, what knowledge gaps still exist regarding which atypical antipsychotic is both safe and beneficial for patients with dementia?  

Due to the limited number of articles included in our study, we did not find a statistically significant difference among the atypical antipsychotics. Meaning, insufficient evidence exists to differentiate between the atypical antipsychotics. This is a gap that exist and can be addressed with access to more studies that are unpublished, which we did not have access to. Also, there is a need to understand the various causes of death as a result of taking these drugs. This can be achieved by utilizing individual, deidentified patient RCT data to perform an individual participant network meta-analysis.

Also, there is no evidence to justify the use of other atypical antipsychotics such as asenapine, clozapine, iloperidone, lurasidone, paliperidone, and ziprasidone, given that there are no eligible clinical trials on these drugs in the treatment of BPSD.  

Is there anything else you would like to add?  

There is a need for the development of safe and effective pharmacological treatments of BPSD since nonpharmacological strategies can be ineffective and are associated with a delayed onset of action in patients with the most severe BPSD threatening to harm themselves or others around them. Additionally, with the increasing aging population, and lack of safe and effective treatments, dementia is a looming public health problem, and this calls for a national or global action. 


Yunusa I, Alsumali A, Garba AE, et al. Assessment of Reported Comparative Effectiveness and Safety of Atypical Antipsychotics in the Treatment of Behavioral and Psychological Symptoms of DementiaA Network Meta-analysis [published online March 22, 2019]. JAMA Netw Open. 2019;2(3):e190828. doi:10.1001/jamanetworkopen.2019.0828

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