May 4, 2016

Agitation is a common symptom of Alzheimer’s disease, and safe and effective treatments for the condition are lacking. Now, a preliminary study has found that a combination of two drugs may be relatively safe and effective in easing the agitation of Alzheimer’s.

The findings are important since behavioral problems like agitation and aggression are a major source of distress for patients and caregivers, and are often the reason why people with Alzheimer’s are moved from the home into a nursing home. They can also hasten the progression to severe dementia and death. Better treatments are needed for such behaviors, which affect more than 90 percent of people with Alzheimer’s.

The study looked at two drugs: dextromethorphan, a cough suppressant, and quinidine, a drug for irregular heart rhythms. The combination is currently used to treat a brain condition unrelated to Alzheimer’s that causes emotional outbursts.

For the study, researchers at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas divided about 200 men and women with probable Alzheimer’s into two groups. Half got the drug combo for five weeks, while the others got a placebo dummy pill.

After five weeks of treatment, those taking the drug combo had fewer periods of agitation, and the agitation was less severe.

After 10 weeks of treatment, 45 percent of those who received the drugs showed improvements in agitation, compared with 21 percent of those receiving a placebo. The drugs did not appear to improve cognition or lead to undue sedation. The findings appeared in JAMA, from the American Medical Association.

Scientists are not sure why these drugs have a calming effect, though they seem to alter levels of brain chemicals like glutamate, serotonin and norepinephrine that affect emotions and may also play a role in Alzheimer’s disease. The drugs may also have pain-relieving effects.

Non-drug treatments are recommended as the first line of treatment for behavioral problems from Alzheimer’s. There is no substitute for good supportive care and knowledgeable, compassionate caregivers.  Having people with Alzheimer’s spend at least 60 minutes a week in activities that they enjoy, for example, has been shown to have calming benefits. Music, art and pet therapy may also help to ease stress and anxiety, although none of these treatments is a cure.  Regular medical and dental care is also essential to rule out pain and other health problems that may be increasing agitation.

Current drugs to ease the memory and thinking problems of Alzheimer’s, such as Aricept, are no more effective than a placebo in easing symptoms like agitation, studies have shown. To treat behavioral problems, doctors often prescribe antipsychotic drugs, but they can have severe side effects, including an increased risk of heart attacks and strokes, and can accelerate memory decline. They may also cause sedation and are often not effective in reducing agitation.  The antidepressant drug citalopram (brand name Celexa) has also shown some benefits for easing the agitation of Alzheimer’s.  Similar antidepressants, called selective serotonin reuptake inhibitors (SSRIs), may also successfully treat depression and anxiety.

The combination of quinidine and dextromethorphan seemed to be safer than current antipsychotic drugs, with fewer side effects. Side effects for the drug combo included an increased risk of falls, stomach upset and urinary tract infections.

In an editorial accompanying the study, experts called the results “encouraging.” More research is needed to confirm the findings, but they suggest that the combination might be a useful tool for easing agitation in people with Alzheimer’s.

“Pending further evidence, there is a reasonably strong case to prioritize dextromethorphan-quinidine as an off-label treatment for agitation, possibly as a safer alternative to atypical antipsychotics,” wrote the editorial authors, from King’s College London.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Sources: Jeffrey L. Cummings MD, ScD, Constantine G. Lyketsos MD, MHS, Elaine R. Peskind MD, et al: “Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia.” JAMA Sept. 22-29, 2015.

Clive Ballard MD, Samantha Sharp, BSc, Anne Corbett, PhD, et al: “Dextromethorphan and Quinidine for Treating Agitation in Patients With Alzheimer Disease Dementia” (editorial). JAMA Sept. 22-29, 2015.