Integrated Approach Best for Alzheimer's-Associated Agitation
by B. Gilbert and L. Marcellin, MD, MPH June 26, 2014;

Non-cognitive neuropsychiatric signs of dementia and Alzheimer's disease, including agitation, may lead to excess morbidity and mortality, greater healthcare use, and earlier nursing home placement, along with caregiver stress, depression and difficulty with employment.

“Non-cognitive neuropsychiatric symptoms NPS are probably the most complex, stressful, and costly aspects of care, bringing about frequent hospitalizations, early elderly care facility placement, and increased mortality," Helen Kales, MD, of the University of Michigan in Ann Arbor told Psychiatry Advisor. “Because these behaviors are really stressful and difficult … to deal with, they pose threats to caregivers' own health, employment income and quality of life.”

According to Kales, agitation the type of symptom associated with Alzheimer's disease (AD), with over 20% of outpatients with dementia and 40% to 60% of those with dementia in care settings exceptional symptom.

The incidence of agitation also increases with AD severity and gets to be more common as the disease progresses.

Anti-psychotics for NPS symptoms

Currently, there aren't any FDA approved treating neuropsychiatric symptoms of AD, however, anti-psychotics can be used to control symptoms.

“Antipsychotics show only modest efficacy in improving symptoms like aggression and agitation and quite often carry substantial risks (like falls, over- sedation, worsened memory problems as well as mortality),” said Kales.

D.P. Devanand, MD, of Columbia University in New York and colleagues, evaluated the effect of citalopram on agitation compared with placebo inside Citalopram for Agitation in Alzheimer Disease (CitAD) randomized clinical trial.

Citalopram proved to be moderately superior to placebo on some indicators of efficacy, the study found.

“However, two-thirds of the way from the study, the FDA designed a new recommendation that elderly patients mustn't be on a citalopram dose higher than 20 mg daily, as it may lead to QT prolongation on the electrocardiogram,” Devanand said.

“The study continued with citalopram 30 mg every day dosing but with additional EKG monitoring, and QT prolongation was, in fact, observed for the EKG in patients receiving citalopram. Therefore, while citalopram showed efficacy at 30 mg daily it remains unclear in the event the lower dose of 20 mg daily might have had a comparable effect.”

The effect of discontinuation on agitation

Currently, there is a federal mandate to discontinue antipsychotics among patients with dementia after four months of treatment, so doctors want to make the case to keep treatment with antipsychotics for all those with AD and agitation.

In the Antipsychotic Discontinuation in Alzheimer's Disease (ADAD) trial, Devanand and colleagues evaluated the consequences of continuing versus discontinuing risperidone in patients with AD who had agitation or psychosis at eight U.S. medical trial sites.

The investigators treated 180 patients openly with risperidone for four months, and then 110 responders were randomly allotted to risperidone or placebo to the next four months. After this four-month period, patients who we had not relapsed were however , randomly assigned to carry on on risperidone or exchange signal of placebo.

During the first four months after randomization, the possibilities of relapse among the placebo group was nearly twice the interest rate of patients within the risperidone group, and inside next four months the relapse risk was 4x greater for placebo in contrast to risperidone.

“The results indicate that patients who improve on risperidone, and probably other antipsychotic medications, need to be for the medication on an extended period of your energy because discontinuation is related to an increased likelihood of relapse in patients who previously replied to risperidone,” Devanand said.

Nonpharmacological management with multidisciplinary teams

Multiple medical organizations and expert groups recommend nonpharmacological strategies since the preferred first-line treatment procedure for managing behavioral symptoms, except in emergency situations when behaviors could cause imminent danger or else compromise safety.

However, nonpharmacological approaches are still underused in standard of care. In an effort to improve NPS management in dementia, Kales and colleagues developed the Describe, Investigate, Create, Evaluate (DICE) approach.

The approach provides clinicians with an evidence-based structured method of addressing the patient's needs.

“We have designed DICE for use by any health care worker and to work effectively within a team-care setting which facilitates coordination among the implementation of medical, medication and nonpharmacologic strategies,” said Kales.

There are a couple of challenges using DICE in current care setting. “Even if health professionals are adequately trained, the present system doesn't allow for reimbursement for time spent in such approaches. So, writing a prescription for a medication that could be modestly efficient at best and dangerous at worst, may be the most common first-line action,” Kales said. “It is our hope that the medical system, perhaps with the new Medicare Pay for Performance guidelines might compensate providers for time spent in DICE or similar approaches.”


Overall, there remains a need for an evidence-informed standardized method of detecting and managing behavioral symptoms that integrates pharmacological and non-pharmacological treatments.




“Under the care of Leo J. Borrell, M.D. since December 2001, I have seen a remarkable improvement in my mother’s condition. She is responding dramatically to the new regiment Dr. Borrell has prescribed”

- Beth Rose


Feb 3, 2008

The Interdisciplinary Team; The Role of the Psychiatrist

by Dr. Leo J. Borrell, featured in Assisted Living Consult for November/December 2006. A HealthCom Media Publication