Keeping Patients With PD on Track With Meds


Lack of adherence to therapeutic regimens for Parkinson disease (PD) is a serious problem that not only greatly impacts health care utilization resources but also throws a monkey wrench in clinicians' attempts to ameliorate disease progression and maintain patients' function and quality of life (QOL).

Lack of adherence to therapeutic regimens for Parkinson disease (PD) is a serious problem that not only greatly impacts health care utilization resources but also throws a monkey wrench in clinicians' attempts to ameliorate disease progression and maintain patients' function and quality of life (QOL). Physicians and risk management and health care utilization analysts have known that many patients with PD are not particularly diligent about medication dosing, but the statistics about the phenomenon and the impact are only recently being clarified.

Among the studies confirming the poor medicating habits of patients with PD at the 10th Congress of the European Federation of Neurological Societies (EFNS) held September 2 to 5 in Glasgow, Scotland, was one by researchers from the health care risk management consultation firm RTI Health Solutions (Research Triangle Park, North Carolina) and GlaxoSmithKline. The team looked at prescription refill patterns from pharmacy claims of 3119 patients in the Integrated Health Care Information Services database who were being treated for PD with levodopa, dopamine agonists, anticholinergics, selegiline, catecholamine-O-methyltransferase inhibitors, or amantadine between January 1997 and December 2004.

Adherence was determined by "medication possession ratio" (MPR), based on documentation of prescription refills. An MPR of 80% designated adherence; a ratio of less than 80% designated nonadherence. Measures were made at 12 months after the initial prescription and at 24, 36, and 48 months.

The research team, led by Heather M. Edin, a researcher at GlaxoSmithKline and the Institute of Medicine of the National Academies, found that 1908 (61.2%) of patients were nonadherent at 12 months. At 48 months, the percentage of nonadherent patients increased to 69.2%. Those patients identified as the least adherent (MPR < 20%) during the first 12 months accounted for more than a third (37.2%) of all nonadherent patients and 22.7% of the entire cohort, the investigators reported.

The researchers noted that the trend is problematic for outcomes in patients with PD and for the economics of health care. Not surprisingly, physical health, mental status, and QOL tend to worsen faster in patients with PD who don't take their medications properly.

Another related study reported at the EFNS congress that also was led by Edin--this time with collaboration from researchers at the College of Pharmacy at Ohio State University in Columbus and the Division of Neurology at Duke University School of Medicine in Durham, North Carolina--found that patients who adhered to therapy were 67% less likely to have worsening symptoms than were nonadherent patients. The findings confirm those of the investigative team of Katherine A. Grosset, MBChB, general and hospital practitioner, and Donald G. Grosset, MBChB, MD, consultant neurologist in the Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland.

Their latest study on this issue demonstrated that patient education and drug regimen monitoring was helpful in maintaining adherence and consequently preventing patients' health from declining. While previous studies1,2 conducted by the Grossets, both of whom are specialists in PD, have confirmed the problem, the present study, reported at the EFNS congress, provided a solution.


After conceding that many patients with PD medicate erratically, the Grossets gathered 83 patients for study participation and divided them into 2 groups. Forty-three (52%) were randomly selected to receive guidance about how to medicate "accurately and regularly" and were educated about the importance of medication adherence. The remaining 40 (48%) of patients acted as controls. Actual medication use in both groups was documented using a medical event monitoring system (MEMS), which is an electronic pillbox that records the date and time that a dose is taken.

The mean rate of timing compliance (ie, taking the correct dose of medication at the correct time) at baseline was 17% for the intervention group and 21% for the control group. After the intervention, the mean timing-compliance rate increased to 39% in the intervention group and decreased to 20% in the control group. The Unified Parkinson's Disease Rating Scale score for motor effects improved somewhat in the intervention group (mean change, 20.5) but deteriorated in the control group (mean change, +5).


The researchers confirmed findings from earlier studies1,3 showing that the more medication doses a patient must take daily, the poorer the adherence to the therapeutic regimen.

"One of the problems in treating patients with advancing PD is that they often are on several different medicines and taking multiple tablets in a day," Katherine Grosset told Applied Neurology. Drug regimens can be quite complicated, such as when different tablet strengths are required, she explained. "For example, if the patient is prescribed ropinirole [Requip] 8 mg tid, patients have to take one 5-mg tablet and three 1-mg tablets, or a 5-mg, a 2-mg and a 1-mg tablet." Grosset noted that one patient in her recently reported study had to use 7 MEMS bottles to keep track of medication use.

A more convenient drug regimen, aggressive patient education about the whys and hows of medication use, and monitoring of adherence using a MEMS or similar device may help patients with PD stay on track with their therapy, the team concluded.

"Showing patients their MEMS data is helpful because, as our experience has shown, how patients report taking their medication and how they actually take it as recorded by the MEMS differs." Grosset was referring to results of a study2 published in the October 2006 issue of the Journal of Neurology, Neurosurgery, and Psychiatry that revealed that adherence data based on self-reports, a visual analog scale (VAS), and simple tablet-count monitoring in patients whose drug regimen adherence rate was 80% or greater jibed with MEMS data. The actual median adherence rate based on MEMS data was 98%. However, adherence data based on self-reports and simple tablet-count monitoring of patients whose drug regimen adherence rate was less than 80% differed greatly from MEMS data. Whereas these patients claimed to adhere to their drug regimen (rate, 100% according to self-report/VAS and 90% according to simple pill count), MEMS data showed a median adherence rate of 69%.

Ironically, but not surprisingly, more of those patients who reported being undertreated were undermedicated than were those who adhered to their drug regimen (38% vs 23%). The Grossets and their coauthors suggested that this scenario can aggravate issues related to health care resource utilization, drug use, and adherence. The treating physician might increase drug therapy in the patient who complains of undertreatment, "with the potential for further divergence between prescribed and actual medication intake." In this published study, the team concluded that an electronic pill-monitoring device, such as a MEMS, might be the best way to go for the patient and the physician in maintaining therapeutic adherence in the management of PD.

REFERENCES1. Grosset KA, Bone I, Grosset DG. Suboptimal medication adherence in Parkinson's disease. Mov Disord. 2005;20:1502-1507.
2. Grosset KA, Bone I, Reid JL, Grosset D. Measuring therapy adherence in Parkinson's disease: a comparison of methods. J Neurol Neurosurg Psychiatry. 2006;77:249-251.
3. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296-1310.

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