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DOI 10.1007/s40120-016-0046-4
ORIGINAL RESEARCH
Results: Seventy patients were followed up, complications (dyskinesia and fluctuation) and
showing a decrease in medicine-related educational attainment [2].
problems (1.67 ± 1.34 to 0.8 ± 0.9 (p\0.001), Therapy for PD is effective in the treatment
positive impact on adherence (from 37 to 10 of motor symptoms, but it does not prevent the
non-adherent patients, p\0.001), QoL disease’s progression. The worsening of motor
improvement related to emotional wellbeing symptoms associated with the occurrence of
(p = 0.012) and autonomic disorder. Most non-motor symptoms evolves progressively.
interventions were performed directly with the This situation leads to dosage increase and
patients (73.8%), including non-pharmacological need of new medication. Some
guidance (28.5%), pharmacological guidance antiparkinsonians, mainly levodopa, develop
(24.3%) and rescheduling (13.6%). motor complications (fluctuation and
Conclusions: To carry out MTM with PD dyskinesia) in the long term, making the
patients, the pharmacist’s expertise needs to treatment complex, increasing the demands
transcend the technical knowledge about the for care and more expensive and invasive
PD pharmacological treatment. The study procedures [5, 6].
showed a positive effect with a decrease in the As a result of the treatment, PD patients can
medicine-related problems after the experience medicine-related problems, which
interventions, especially improving adherence are also called DRPs—drug-related problems. ‘‘A
and patients’ QoL. DRP exists when a patient experiences (or is
likely to experience) either a disease or
Keywords: Parkinson disease; Pharmaceutical symptom having an actual or suspected
care; Medication therapy management relationship with drug therapy’’ [7].
Medicine-related problems include issues
related to medicine effectiveness, adverse
INTRODUCTION
reactions and non-adherence to the treatment.
Parkinson’s disease (PD) is a neurodegenerative Non-adherence to the treatment is one of the
disease characterized by motor manifestation, most common medicine-related problems in
autonomic disorder, sensorial symptoms and patients who suffer from chronic diseases. It has
neurological disorder that compromises the been estimated that the PD patients’ adherence
patient’s quality of life (QoL) [1, 2]. to the treatment is only 39%, compromising the
Due to the progressive nature of the disease, benefits of the therapy [6]. Younger patients,
the patient’s QoL is compromised in physical, patients with complex therapeutic regimens
mental/emotional, social and economic aspects. (several pills per day), high depression, and low
The most common and relevant factors QoL are less adherent to the antiparkinsonian
reviewed in the literature about the worsening treatment [8–10]. Clinical consequences of
of PD patients’ QoL were bradykinesia, tremor, non-adherence to the antiparkinsonian
rigidity, postural instability, gait disorder, pain, treatment include loss of motor functions and
fatigue, depression, and sexual and cognitive reduction in QoL [11, 12]. The commitment of
disorders [3, 4]. A Brazilian study showed that health professionals and patients together
the major QoL determinants include mood contributes to improvement of treatment
disorder (mainly depression), disability, PD adherence [5, 8, 13]. Furthermore,
Neurol Ther (2016) 5:85–99 87
knowledge about PD and its treatment. caregivers that did not report these symptoms
Additionally, all the parameters included in were classified as on-state. Non-motor
the assessment were agreed between pharmacist symptoms (e.g. autonomic disorder, insomnia,
and patient prior to the study in order to hallucinations) were classified as relief or
standardize the data collection. The provision non-relief. These data were collected
of the MTM service considered the patient’s throughout the six appointments.
health needs related to PD and co-morbidities. After analyzing the aforementioned data, the
The data record forms were designed based on pharmacist identified potential
the Pharmacotherapy Workup and the Dader medicine-related problems reported by the
methods [16, 22–24]. The form contained patients in the appointments. The problems
information about demographics, were classified according to Cipolle et al. [16] as
pharmacotherapy, lifestyle, co-morbidities, indication, effectiveness, safety and adherence.
memory, and cognition, PD symptoms, and QoL. When a medicine-related problem was
Pharmacotherapy data (indication, dose, identified, the pharmacist designed an
posology, scheduling, and reports on the intervention procedure in order to solve it
access to medicines) were collected from the based on clinical, familiar, and social context
medical prescription, patient diary [25] and all data; the latter two were collected using the
medicines (over-the-counter and prescription genogram [28, 29] and ecomap [30–32] tools.
medicines) brought by the patient to the The interventions to resolve the detected
appointment with the pharmacist. Such data medicine-related or other health problems
were supplemented with information from the referring to PD were targeted to
medical chart. Adherence was measured patients/caregivers and/or doctors. The
through clinical interviews (open questions interventions targeting the patients/caregivers
made during the interview in the first and included counseling, rescheduling, education
sixth appointments) and by the Morisky measures, changes in the pharmacotherapy
questionnaire (self-reporting by answering (only OTC medicines), and referral to other
closed questions in the first, third, and sixth healthcare services (e.g., phonoaudiology,
appointments) [26]. physiotherapy). The interventions were held
Lifestyle data were collected in the clinical with the support of written instructions referring
interviews and from the patient’s diary. to verbal counseling, educational material,
Co-morbidity data were collected from personalized calendar of the pharmacological
medical charts and test results brought by the treatment and the pharmacotherapeutic diary
patient to the appointments. Memory and (meal and medication reminder). The
cognition impairment data were collected with interventions targeting the doctors included
the mini–mental state examination test [27] suggestions of changes in the therapeutic
which was applied in the second appointment. regimen of prescription medicines (addition,
The PD symptoms assessment was based on the discontinuation, posology, or dosage form). The
patients’ and/or caregivers’ perception about doctors were informed about the
the symptoms’ progression. The patients or recommendations by means of letters based on
caregivers that reported bradykinesia, tremor the best evidence available collected from
and/or rigidity during the period between their searches in the databases Pubmed, Cochrane,
doses were classified as off-state. The patients or Bireme, and MicromedexÒ.
Neurol Ther (2016) 5:85–99 89
In order to record the follow-up data, the Agreement was used to analyze the
SOAP (Subjective, Objective, Assessment Plan) concordance between the Morisky Medication
[33] was used. Adherence Scale and the clinical interviews.
Confidence intervals of 95% and values of
Main Outcomes Analyzed p\0.05 were considered significant. The data
analysis was carried out using the software SPSS
The effects of MTM upon PD patients were Statistics 15.0 for Windows.
assessed considering QoL improvement or
maintenance as a primary outcome. QoL was Ethical Issues
measured by means of the Parkinson’s Disease
Questionnaire (PDQ-39) in a legitimate This research was approved by the Human
Brazilian Portuguese version. This is a Ethics Committee at the Federal University of
PD-specific questionnaire that consists of 39 Santa Catarina with Institutional Approval No.
questions distributed between eight multi-item 1963/2011. All ethical aspects were in
domains: mobility (ten questions), activities of accordance with the Declaration of Helsinki of
daily living (six questions), emotional wellbeing 1964, as revised in 2013.
(six questions), social support (three questions),
body discomfort (three questions), stigma (four
RESULTS
questions); cognition (four questions); and
communication (three questions) [34–36]. Seventy of the 161 PD patients registered in the
Primary outcomes include changes in the SCPA were included in the study. The main
general and specific PDQ-39 domain and reason why some patients declined to
scores. Secondary outcomes include changes in participate was difficulty to get to the
the On/Off state of motor symptoms and relief pharmacy. Fifty-one of the 70 participating
of non-motor symptoms from the patients completed the expected 6 months of
patient’/caregiver’ perspective, as well as MTM. Figure 1 shows the sampling flowchart.
solutions to medicine-related problems,
especially those related to adherence.
Data Analysis
is worth noting that there were differences in the that PD medicines quickly lose their
results of the adherent patients at the end of the effectiveness and cause long-term side effects.
MTM process (appointment 6) between the These characteristics create the necessity of a
Morisky and Clinical Interviews methods (kappa comprehensive approach towards a constant
value = 0.304; a 95%, p = 0.017); despite a monitoring of the pharmacological therapy and
considerable concordance (but not high) found the PD effects on the patients’ QoL [37]. These
between the methods in the first appointment characteristics consider QoL as a primary
(kappa value = 0.333, a 95%; p = 0.007). outcome in PD [3]. Furthermore, because of
the particularities of the disease, individualized
DISCUSSION interventions are required.
As previously indicated, most of the
Parkinson’s disease is a complex condition due interventions were performed in a period of up
to the progressive nature of its motor and to 2 years and between 5 and 10 years after the
non-motor symptoms, in addition to the fact diagnosis, as these are the two critical periods in
94 Neurol Ther (2016) 5:85–99
the PD patient’s life. Up to 2 years, the patient that the clinical practice focuses on motor
experiences a period of adaptation and rather than non-motor symptoms, which
acceptance of the diagnosis. In the period remain underestimated and untreated.
from 5 to 10 years, the PD patient faces Similarly to other studies, our results show
complications related to the treatment and the that non-adherence is the main medicine-related
disease’s progression [38]. problem. This finding highlights the importance
Based on MTM, the analysis detected health of health professionals following up the patient’s
problems related and not related to medicines. Our medication use in order to investigate if the
results demonstrate that even though most of the symptoms are a consequence of non-adherence
identified health problems were not or of the disease’s progression. In this way,
medicine-related, they could be resolved by unnecessary dosage change or addition of new
pharmaceutical interventions. For instance, medicines can be avoided, reducing the risk of
autonomic disorders were one of the most adverse events [8, 14, 42, 43].
frequent problems not related to medicines and One of the key factors to improve adherence
can result from the disease’s progression and/or is the patients’/caregivers’ knowledge about the
antiparkinsonian medication side effects. Their disease and awareness of the consequences of
negative effects on the PD patients’ QoL were also discontinuing the medicine. This is the reason
mentioned in other studies [39–41]. The symptoms why it is crucial to consider the patient as an
can be relieved by means of nonpharmacological active partner in the healthcare process. Good
measures or by OTC medicines. Therefore, this communication between the health
type of interventions became important in the professional and the patient is fundamental
pharmaceutical practice. for effective clinical practice and for adherence
Although there are few studies about improvement. Some causes of non-adherence
medicine-related problems in PD patients, the include the patient’s search for other treatment
results of the present study were similar to those options, especially for the cure (mysticism,
of other published papers. Our results show that beliefs), and discontinuation of the treatment
the medicine-related problems were more in case-positive effects are not experienced.
frequently related to non-adherence, adverse Moreover, our results corroborate those
reactions, necessity of additional medication reported by Navarro-Peternella and Marcon
and underdose. In another study carried out in [44] ,which demonstrated the necessity of
community pharmacies, most DRPs individualized professional interventions based
concentrated on the need of additional on actions that represent the real needs of the
medicines (26.3%) and adverse reactions PD patient and/or caregiver. Guidance and
(12.4%) [14]. In another study at a nursing information about the disease, its progression,
home, most DRPs concentrated on unnecessary and ways of facing it are fundamental for
medications (28%) and underdose (14%) [15]. patient, caregiver, and family. The healthcare
According to Schröder et al. [14], underdose services for PD patients must aim to minimize
may be associated with the prevention of the limitations resulting from the disease’s
adverse reactions to dopaminergic progression and contribute to the
medications. Moreover, the medicine-related improvement or maintenance of their QoL [3].
problems associated with the necessity of Regarding the outcomes of the MTM service
additional medication may stem from the fact related to QoL, and despite the short period of
Neurol Ther (2016) 5:85–99 95
analysis, this study produced a positive clinical evaluates adherence as the simple act of taking
impact. It is worth remarking that one of the the medication (compliance), the clinical
health professional’s biggest challenges is to interview method sees the patient as an active
prepare his/her therapeutic plan in a way that partner in the adherence process and considers
the patient’s QoL reaches a level that can be the patient’s will to collaborate with the
considered good [44, 45]. treatment (concordance) [48, 49]. In this
The improvement of the PDQ-39 score sense, once the most practical method to
regarding emotional wellbeing after the MTM evaluate the treatment adherence, especially
process confirms the previously reported for elderly patients, is by interviewing the
humanistic positive impacts of MTM on the patients or their caregivers [50], the adherence
patient’s life [18, 46]. During this process, the improvement assessed in our study can be
patient is seen as an individual with rights, considered a significant result of the MTM
knowledge, and experience and is treated as a service for PD patients.
partner in the planning of his/her care, being
responsible for taking the final decision in the Limitations
therapeutic conduct [16]. This horizontal
relationship between pharmacist and patient This study was conducted at a public
generates a transparent environment of trust community pharmacy which is the only
and credibility necessary for establishing a outpatient setting that dispenses
therapeutic alliance. In addition the antiparkinsonian medicines in the city, except
perception of the patient as the central levodopa which is dispensed at primary
figure of the pharmaceutical care within their healthcare pharmacies. As we used the
family and social context, singularity, convenience sampling method including only
complexity, and subjectivity contributed to a the patients that we could contact instead of a
more comprehensive care. This way of random sample, a selection bias may have
generating healthcare may have contributed to occurred. However, the characteristics of the
the improvement of the PD patient’s wellbeing. population under analysis are similar to those
MTM was not able to improve or stabilize the reported in other studies [51–55].
patients’ motor symptoms. A contributing The sample loss can be considered a limiting
factor is the absence of medicines that actually factor of the statistical analysis. Nevertheless,
delay the disease’s progression, which the results can be considered relevant from a
undoubtedly leads to the worsening of the clinical point of view, once there was a decrease
motor symptoms. Nevertheless, MTM has a from 42 to 20 in the number of non-adherent
considerable impact on the relief of patients. Since 15 patients did not complete the
non-motor symptoms, thus contributing to MTM process, the number of interventions per
the PD patients’ QoL. patient over the 6 months may have been
Variations in the results of adherence underestimated.
assessed by different methods were also Another limitation of the study was the
reported by Perseguer-Torregrosa et al. [47]. unavailability of a neurologist. In an MTM
This difference reflects the way that each service, this partnership is very important to
method considers the patient’s role during the achieve the desired outcomes, since many
therapy. While the Morisky questionnaire interventions need the doctor’s collaboration.
96 Neurol Ther (2016) 5:85–99
The quantitative data on humanistic aspects which contributed to improve this manuscript.
were out of the scope of the study. Therefore, No funding or sponsorship was received for
further studies are needed for statistical this study or publication of this article. All
analyses. For the reason that some named authors meet the International
interventions to improve adherence were Committee of Medical Journal Editors (ICMJE)
related to changes in the medication regimen, criteria for authorship for this manuscript and
it was not possible to analyze whether the take responsibility for the integrity of the work
outcomes were driven by medication changes as a whole, and gave final approval to the
or compliance. version to be published. The concept and
design of the study were developed by Foppa
and Chemello. Foppa was primarily in charge
CONCLUSION
of the data collection; and Chemello, Foppa
In order to carry out an MTM service with PD and Vargas-Peláez were primarily responsible
patients, the pharmacist’s expertise needs to for the data analysis. The manuscript was
transcend their knowledge about the primarily written by Foppa with assistance
pharmacological treatment. from Chemello and Farias, and was revised by
Non-pharmacological measures are Chemello, Vargas-Pelaez, and Farias. This paper
fundamental to relieve non-motor symptoms is part of Foppa’s master’s thesis with the title
(autonomic and neurological disorders), which ‘‘Qualification of clinical pharmaceutical
are not assessed by the PDQ-39 but have an service based on the Medication Therapy
important impact on the PD patients’ QoL. The Management for patients with Parkinson’s
changes in the individual, family, and social disease’’ advised by Farias and co-advised by
dynamics caused by the disease must be also Chemello.
understood by the pharmacist so that he/she
can perform a service based on a comprehensive Disclosures. Aline Aparecida Foppa, Clarice
care perspective. Chemello, Claudia Marcela Vargas-Peláez and
The interventions resulting from the MTM Mareni Rocha Farias have nothing to disclose.
service contributed to improve or to maintain
Compliance with Ethics Guidelines. This
the PD patients’ QoL, especially their emotional
research was approved by the Human Ethics
wellbeing. MTM had a positive effect in the
Committee of the Federal University of Santa
decrease of medicine-related problems,
Catarina with Institutional Approval No.
especially regarding improvements in the
1963/2011. All ethical aspects are in
treatment adherence. These results represent
accordance with the Helsinki Declaration of
clinical and humanistic outcomes of the MTM
1964, as revised in 2013. Informed consent was
service.
obtained from all the participants in the study.
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