Nav: Home

IU, Regenstrief study explores adherence and tolerability to Alzheimer's medications

April 11, 2017

INDIANAPOLIS -- Researchers from the Indiana University Center for Aging Research and the Regenstrief Institute have performed the first study conducted in the United States under real-world conditions comparing patient adherence and tolerability to a class of drugs known as cholinesterase inhibitors. Although there are no known cures for Alzheimer's disease or other dementias, drugs in this class may delay or slow the progression of symptoms in some individuals.

All three cholinesterase inhibitor medications approved by the US Food and Drug Administration require titration with patients working up from an initial dose to a target dose to receive full benefit. According to the manufacturers this can be achieved in 4 to 8 weeks. Yet, surprisingly, the new study, published online ahead of print in the Journal of the American Geriatrics Society, found that by 18 weeks, only one-half of individuals on any of the three drugs were continuing to take them.

"While these medications do not change the course of the disease, by not getting patients to target doses, we aren't optimizing the potential benefits these medications may provide," said IU Center for Aging Research and Regenstrief Institute scientist Noll Campbell, PharmD, who led the study. "Unlike the clinical trials conducted by drug companies for FDA approval, this study was conducted with participants who were taking an average of 8 other medications - what we would call a 'real-world' population -- individuals who are sicker than those who typically participate in drug company trials. Having a better understanding of those to whom the drugs are targeted may provide us with greater insight into how to increase benefits and reduce risk."

During the study, just over half of all participants experienced a side effect which contributed to the decision to stop the medication. Muscular-skeletal side effects (general pain and muscle cramps) and neurologic side effects (dizziness, nightmares, headaches) were just as common as gastrointestinal side effects (vomiting, nausea, diarrhea). Side effects primarily occurred at starting dose or early on in treatment.

The 196 study participants were patients of memory practices in four large metropolitan Indianapolis health care systems. Three-quarters of those patients followed in the study were female, 31 percent were African-American, and 73 percent had completed high school. Mean age was 80. There was no difference in demographic or clinical characteristics by drug, which were randomly prescribed.

No variation was found in tolerability or adherence to the three drugs by sex, race, education or age.

Despite the high rate of side effects, the only reason for discontinuation that was different between the medications studied was cost. Individuals were more likely to start and remain on donepezil. This drug is most consistently included as a preferred medication (thus lowest cost to the patient) under many U.S. drug coverage plans.

Approximately 14 percent of those patients who were prescribed galantamine and 17 of those prescribed rivastigmine -- the other two drugs in the class -- stopped for cost reasons although some switched to the covered donepezil and continued to be followed by the researchers to determine tolerability to the drug. Without insurance coverage, all three drugs are similarly priced.

"Physicians should be aware of the impact of side effects, many of which are shared with other medications that the patient is taking, on both the adherence to the medication and quality of life," Dr. Campbell, who is on the faculty of the Purdue University College of Pharmacy, said. "While these drugs aren't the answer to Alzheimer's disease, improving tolerability and adherence may reduce the complications of the disease."

Over the 18 week duration of the study target dose was achieved by 53 percent of those taking donepezil. Merely 5 percent of those prescribed galantamine and 19 percent of those prescribed rivastigmine reached the dose needed for maximum effect.

"The current US drug trial approval process is just too long -- typically 17 years -- and inefficient with only a 14 percent hit rate from discovery to successful delivery," said study senior author Malaz Boustani, MD, MPH. "We need to test the efficacy of drugs in real-world populations -- as we did in this study -- at the earliest phase of clinical trials". Dr. Boustani is the founder of the Indiana Clinical and Translational Sciences Institute's IU Center for Health Innovation and Implementation Science, deputy director of the IU Center for Aging Research, an IU School of Medicine professor, and a Regenstrief Institute investigator.
-end-
Authors of "Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial," in addition to Dr. Campbell and Dr. Boustani are Anthony J. Perkins, MS, of IU Center for Health Innovation and Implementation Science and Indiana CTSI; Hugh C. Hendrie, MB, ChB, DSc, Nicole Fowler, PhD, and Christopher M. Callahan, MD, of IU Center for Aging Research, Regenstrief Institute and IU School of Medicine; Sujuan Gao, PhD, Todd C. Skaar, PhD, and Lang Li, PhD, of IU School of Medicine.

The study was funded by Agency for Healthcare Research and Quality grant R01HS019818-01.

Indiana University

Related Clinical Trials Articles:

Review evaluates how AI could boost the success of clinical trials
In a review publishing July 17, 2019 in the journal Trends in Pharmacological Sciences, researchers examined how artificial intelligence (AI) could affect drug development in the coming decade.
Kidney patients are neglected in clinical trials
The exclusion of patients with kidney diseases from clinical trials remains an unsolved problem that hinders optimal care of these patients.
Clinical trials beginning for possible preeclampsia treatment
For over 20 years, a team of researchers at Lund University has worked on developing a drug against preeclampsia -- a serious disorder which annually affects around 9 million pregnant women worldwide and is one of the main causes of death in both mothers and unborn babies.
Underenrollment in clinical trials: Patients not the problem
The authors of the study published this month in the Journal of Clinical Oncology investigated why many cancer clinical trials fail to enroll enough patients.
When designing clinical trials for huntington's disease, first ask the experts
Progress in understanding the genetic mutation responsible for Huntington's disease (HD) and at least some molecular underpinnings of the disease has resulted in a new era of clinical testing of potential treatments.
New ALS therapy in clinical trials
New research led by Washington University School of Medicine in St.
Telemedicine helps improve participation in clinical trials
Videos and creative uses of other visuals provide a novel way to obtain informed consent during clinical trials to improve participants' understanding and retention of trial information, according to a study by Nemours Children's Health System presented at the American Thoracic Society (ATS) Annual Conference.
Not enough women included in some heart disease clinical trials
Women are underrepresented in clinical trials for heart failure, coronary artery disease and acute coronary syndrome but proportionately or overrepresented in trials for hypertension, atrial fibrillation and pulmonary arterial hypertension, when compared to incidence or prevalence of women within each disease population, according to a study in the Journal of the American College of Cardiology.
BU: Obese patients underrepresented in cancer clinical trials
A new review by Boston University School of Public Health researchers found that less than one-fifth of participants in cancer-related clinical trials are obese.
Are women really under-represented in clinical trials?
Several studies have reported a lack of gender diversity in clinical trials, with trials including mostly adult males; however, a recent review of publicly available registration data of clinical trials at the US Food and Drug Administration for the most frequently prescribed drug classes found no evidence of any systemic significant under-representation of women.
More Clinical Trials News and Clinical Trials Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.