Parkinson Medication Adherence is Suboptimal

Most drugs for Parkinson have complex dosing regimens, contributing to nonadherence.

Patient adherence to prescribed therapy, medication dosage, and timing is vital in the therapeutic management of Parkinson disease (PD). Most of the drugs available for treating PD are administered in tablet or capsule form, often involving multiple daily doses with complex dosing regimens. This contributes to suboptimal adherence.

Nonadherence with medication is associated with poor symptom control and poor patient-perceived response to therapy, and this indirectly increases health care costs. Treatments that require fewer daily doses and guiding patients about continuous therapeutic coverage both have the potential to improve patient compliance.

We identified relevant studies for the prevalence of medication adherence in PD by searching MEDLINE (1946 - July 31, 2014), EMBASE (1947 - July 31, 2014), and Cochrane Library (1946 - July 31, 2014) databases. In our review of the medical literature, we included 9 scientific papers that reported the prevalence of significant medication noncompliance in PD, using standard definitions, to vary between 10% and 67%. This variation partly reflects differences in defining what clinically significant medication adherence is, the methods used to estimate the scale of the problem, and the underlying population heterogeneity.

The predictors of noncompliance included age (young and elderly), stage of disease, knowledge of the disease, complexity of posology, disease comprehension,  patients with multiple comorbidities, those who experienced multiple changes in antiparkinson therapy, cognitive function, and family support.^1-3

Although levodopa is considered the gold standard for treating the dopamine deficiency state in PD, the plasma half-life of levodopa plasma is very short, requiring multiple daily doses to keep plasma levels therapeutic. Further, this multiple daily dosing results in marked plasma drug concentration fluctuations, which are matched, as the disease progresses, to swings in the therapeutic response (“wearing-off” phenomenon).⁴ This can create problems with drug adherence.

The use of long-acting prolonged release once daily preparations of dopamine agonists (pramipexole, ropinirole, rotigotine) theoretically can increase patient adherence by simplifying the drug regimen while recognizing that in the mid to late stages of the disease the use of levodopa will become inevitable.

The consequences of noncompliance for the individual patient may include withdrawal symptoms, which in severe cases (with total cessation of therapy) can lead to the parkinsonism-hyperpyrexia syndrome.⁵ On the other hand, overdosing as a manifestation of noncompliance with prescribed therapy can lead to dyskinesia or psychiatric complications, such as hallucinations and psychosis, and is a key component of the dopamine dysregulation syndrome.⁶

Noncompliance is associated with an increased burden on health care systems because of greater resource usage compared with the compliant population.⁷

Several interventions that have been applied generically to patients with chronic diseases, in an attempt to improve patient compliance, can be applied to cases with PD as well. These methods include the development of an individualized treatment plan that simplifies the complex drug regimen as far as possible,⁸ clearly explaining beforehand about the possibility of adverse effects that can be otherwise surprising and off-putting to the patient,⁹ providing compliance aids such as medication calendars or dispensing systems such as blister packs/dosette boxes,⁸ and tying the medication-taking process to other daily routines to improve timing compliance.¹⁰

Addressing comorbidities that may contribute to nonadherence in PD is also important. Psychiatric and cognitive problems in PD are common in the later stages of the disease.^11,12 Patients with depression are 3 times more likely to have poor adherence compared with nondepressed patients,¹³ and patients with PD who have comorbid depression are more likely to have increased health service utilization than those without depression.¹⁴

Finally, the very important contribution that carers of patients with PD make to their well-being is recognized in supporting adherence to an appropriate medication prescription schedule.¹⁵

Key points:

• Suboptimal medication compliance is common in PD and is associated with worse symptom control.

• Nonadherence with prescribed therapy is associated with higher overall health care costs because of greater health care utilization, including more hospital visits.

• The predictors of nonadherence are age (young and elderly), longer disease duration, poor knowledge of their disease, risky behaviors (alcohol, novelty seeking), and complex drug regimens.

• Drug regimens that are simpler and have fewer daily doses offer the prospect of better therapy adherence.

• Dialogue with the patient and family is important to ensure that deviations from the recommended prescription are understood and that all parties reach an informed position.

References:

1. Wei YJ, Palumbo FB, Simoni-Wastila L, et al. Antiparkinson drug use and adherence in medicare part D beneficiaries with Parkinson’s disease. Clin Ther. 2013;35:1513-1525.e1.

2. Grosset KA, Bone I, Grosset DG. Suboptimal medication adherence in Parkinson’s disease. Mov Disord. 2005;20:1502-1507.

3. Sesar A, Arbelo JM, del Val JL. Treatment of Parkinson disease, time and dosage: “does simple dosage facilitate compliance and therapeutic goals?”. Neurologist. 2011;17(6 Suppl 1):S43-S46.

4. Contin M, Martinelli P. Pharmacokinetics of levodopa. J Neurol. 2010;257(Suppl 2):S253-S261.

5. Newman EJ, Grosset DG, Kennedy PG. The parkinsonism-hyperpyrexia syndrome. Neurocrit Care. 2009;10:136-140.

6. O’Sullivan SS, Evans AH, Lees AJ. Dopamine dysregulation syndrome: an overview of its epidemiology, mechanisms and management. CNS Drugs. 2009;23:157-170.

7. Richy FF, Pietri G, Moran KA, et al. Compliance with pharmacotherapy and direct healthcare costs in patients with Parkinson's disease: a retrospective claims database analysis. Appl Health Econ Health Policy. 2013;11:395-406.

8. Bond WS, Hussar DA. Detection methods and strategies for improving medication compliance. Am J Hosp Pharm. 1991;48:1978-1988.

9. Galloway R, McGuire J. Determinants of compliance with iron supplementation: supplies, side effects, or psychology? Soc Sci Med. 1994;39:381-390.

10. Berger BA. Assessing and interviewing patients for meaningful behavioral change: Part 1. Case Manager. 2004;15:46-50; quiz 51.

11. Rojo A, Aguilar M, Garolera MT, et al. Depression in Parkinson’s disease: clinical correlates and outcome. Parkinsonism Relat Disord. 2003;10:23-28.

12. Riedel O, Klotsche J, Spottke A, et al. Cognitive impairment in 873 patients with idiopathic Parkinson’s disease: results from the German Study on Epidemiology of Parkinson’s Disease with Dementia (GEPAD). J Neurol. 2008;255:255-264.

13. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101-2107.

14. Qureshi SU, Amspoker AB, Calleo JS, et al. Anxiety disorders, physical illnesses, and health care utilization in older male veterans with Parkinson disease and comorbid depression. J Geriatr Psychiatry Neurol. 2012;25:233-239.

15. Campbell NL, Boustani MA, Skopelja EN, et al. Medication adherence in older adults with cognitive impairment: a systematic evidence-based review. Am J Geriatr Pharmacother. 2012;10:165-177.