Katherine Grosset*
Adherence to medication among people with Parkinson’s
It is widely known that compliance (also referred to as adherence) to prescribed medicines (taking a medication exactly to doctors’ recommendations) is sub-optimal across many different disease areas.1 However, it was thought that people with Parkinson’s (PwPs) would have high levels of compliance due to the highly symptomatic nature of the condition. We have conducted several studies of medication adherence in PwPs, using several different methods and examining several different factors that may affect adherence.2-6 Our findings support other compliance studies in PwPs that show sub-optimal adherence to Parkinson’s medications.2, 4, 7-10
Simplifying treatment regimens in other diseases is known to improve adherence1, 11 and our findings have shown that once-daily Parkinson’s medications have better adherence rates than medications that are taken more frequently.2, 4 Involving PwPs in therapy decisions and ensuring that they know and are happy with their treatment regimen could also play a vital role in improving compliance intent.3, 4
Categories of non-compliance
Primary non-compliance
In primary non-compliance, the patient does not seek to have the medication dispensed.
Intentional non-compliance includes the rejection of a diagnosis or advice or problems with prescription charges or collection. Medical opinion and patient interpretation may vary from the start of treatment, with patients balancing what they think is necessary for treatment against their concerns for adverse effects, tolerance and dependence.12 In Parkinson’s there can be concerns over improving current symptoms versus future symptom fluctuations. If treatment is recommended when the PwP considers it unnecessary, this can impair compliance.
Unintentional non-compliance may be due to forgetfulness that relates to mild symptoms, co-existent cognitive impairment13, 14 or depression.15, 16
Secondary non-compliance
This occurs later in the treatment pathway and has several sub-categories:
Early discontinuation
Adverse effects are a widely recognised reason for non-adherence and premature medication discontinuation in diseases such as depression17 and Parkinson’s.18 Informing patients of potential adverse effects improves therapy continuation.19 Nausea and light-headedness are common when starting anti-Parkinson’s therapy, particularly with dopamine agonists; and although reduced by slow titration (a gradual dose increase) and/or taking domperidone, clinical trials in Parkinson’s show significant early discontinuation due to adverse effects.18, 20-26
Lack of efficacy also leads to the early discontinuation of treatment. PwPs often report a poor therapy response because they expect an improvement in tremor, but this only occurs in about half of the cases.27 Guidance about the expectations of therapy (improved movements and muscle tone) may reduce secondary non-compliance.
Irregular dosing
The aim of Parkinson’s medication is to mimic physiological dopamine, but peaks and troughs of erratic dopamine replacement – which can occur if medication is not taken on time – may contribute to the development of motor complications later in the disease.28 Our findings have shown that even if overall adherence to medication is good, they are often taken in an erratic and irregular way. It is important that patients know their medication regimen and are educated about the importance of taking their medication on time.4
Overuse of medication
Medication overuse is well recognised, especially for those treatments with addictive properties. A subgroup of advanced PwPs take excess dopamine replacement therapy compulsively despite severe dyskinesia and psychiatric affects.29, 30 Other PwPs overuse dopamine replacement therapy to a lesser degree, in the hope of returning to a ‘normal’ mobility state.31 However, our findings suggest that underuse of Parkinson’s medication is much more common than overuse.4
The bottom line
Tablets do not work if they are not taken32 – indeed we found that motor symptoms were significantly worse in patients with sub-optimal adherence versus those with satisfactory adherence.4 Complex treatment regimes are more difficult to comply with. Once-daily medications have significantly better adherence when compared to medications prescribed more frequently.2, 4, 10 Treatment tolerability, adverse effects and perceived efficacy must also be considered.
Proposed solutions for improving adherence
Non-pharmacological
Concordance
A multitude of interventions to help patients take prescribed medication have been carried out in many disease areas. These include education programmes and physical cues/reminders that ‘advise’ patients on how to take their medication, but such programmes have shown marginal benefit to date.33
PwPs are, however, much more likely to follow a treatment plan if they are involved in the decision-making process.3 Being informed about and understanding the advantages and disadvantages of the different options available to them help them feel assured that they are on the treatment course that is best suited to them.
Pharmacological
Simplifying treatment regimes
It is generally more difficult to take medicines as prescribed if multiple treatments and frequent dosing schedules are required.1 Simplifying treatment regimens has proven beneficial in several disease areas.1, 11
In our work using electronic pill monitoring devices, we have found that the level of compliance deteriorated with increasing doses per day; in particular, it is very difficult to take medicines more than four doses per day on a regular basis4 as there is no set cue to take the medication (such as breakfast, lunch, tea and bedtime). Once-daily medications were taken most consistently.4 Once-daily formulations are currently available for non-ergot dopamine agonists (prolonged release ropinirole and pramipexole, and rotigotine patch) and MAO-B inhibitors (selegiline and rasagiline).
It should be noted that for some once-daily medications, missing a tablet may have more of an effect on symptoms than missing one tablet of a more frequently dosed medication. However, this is medication-specific and dependent on the drug’s half-life (the time it takes for half the substance to decay).
Treating co-morbidities
Patients with depression are three times more likely to have poor adherence.34 This is especially important as depression commonly accompanies Parkinson’s35 and has a major influence on quality of life.36, 37 Cognitive impairment can also influence medicine-taking behaviour15, 16 and, as a result, carers of PwPs play a vital role in ensuring medication is taken properly.
Conclusion
Parkinson’s treatment regimes are often complex, and adherence to medication is suboptimal. There are a number of solutions that can be implemented to help improve adherence, and involving PwPs and their carers in the therapy decision-making process – and ensuring they are happy with, and understand, their treatment regimen – can improve outcomes.
However, pharmacological approaches that make it easier for PwPs to take medicines to the best effect are key for successfully improving compliance. The current once-daily formulations, although often more expensive, should be optimised and the development of more effective long-lasting formulations for the treatment of later-disease stages would be greatly beneficial. It is important to bear in mind, though, that the main advantage of once-daily preparations is that they are once-daily. Their effectiveness and safety profiles are still comparable with other dosing preparations.
References
