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Running head: PARKINSON'S DISEASE TREATMENT 1

Parkinson's Disease Treatment

A Literature Review

Valerie Salazar and Katie Scanlon

State University of New York Institute of Technology

PARKINSON'S DISEASE TREATMENT 2

Parkinson's Disease Treatment A Literature Review

Parkinson’s disease (PD) is a progressive neurological condition caused by the

degeneration of dopamine-producing neurons in the subtantia nigra region of the brain (Lindop,

2012). Dopamine is responsible for relaying messages in the brain to control movements,

specifically smooth coordinated movements (Desilets & LaFontaine, 2013). The progressive

damage of neurons and dopamine-producing cells, or neurodegeneration, is believed to be the

pathology experienced by those with PD (Casey, 2013).

PD symptoms begin gradually, often unilaterally, and worsen with time (Parkinson’s

Disease Foundation, 2014). Main motor symptoms include bradykinesia, rigidity, resting

tremors and postural instability (Lindop, 2012). Impacts of patients’ activities of daily living

include difficulty walking, talking, or even feeding one-self. Non-motor symptoms can present

as emotional or behavioral changes, problems with cognition and memory, sleep disorders,

sexual dysfunction, and sensory deterioration including incontinence, color vision perception,

and decreased sense of smell (Simon, 2012).

Relevance to nursing

The progression and treatment of PD varies patient to patient. Advanced Practice

Registered Nurses (APRNs) play a critical role in the coordination and provision of services as

they are ideally placed to assess, discuss, and address the multitude of issues presented above

(Osborne, 2009). The use of holistic assessments, treatments, and education provided by APRNs

is beneficial to PD patients and their families as they provide consistent, high quality levels of

judgment, discretion, and decision-making regarding clinical care (Osborne, 2009).

Purpose statement


The purpose of this paper is to provide a review of recent literature regarding the

treatments available for PD specifically pharmacologic, non-pharmocologic, and deep brain

stimulation options. The authors will discuss the current state of the science in terms of PD

treatments including gaps in the literature and recent research studies. The selected published

studies and peer reviewed articles will be discussed to provide insight to emerging treatments

and expanding research for PD. A literature review grid can be found in Appendix A.

Method

A conventional literature search was undertaken by the authors through the State

University of New York Institute of Technology’s Cayan Library website and their home

internet services using Google Scholar. The phrases “Parkinson’s Management” and

“Parkinson's Treatment” were entered using the CINAHL, Medline, and Health Source:

Nursing/Academic Edition databases. Resources were included if they were published after

2009, in English, and available in full text without additional cost to the researchers. Papers with

both qualitative and quantitative research studies were included. Selection criteria for data

collection focused on peer reviewed articles and research studies published in nursing academic

journals. Books and book chapters were not selected. Our initial search revealed 1,830 sources.

These results were narrowed to 227 after applying the above criteria to our searches. The final

selection was based on reading abstracts and selecting the most pertinent material.

Results

Motor Symptoms

Non-pharmacological treatment. PD adversely affects an individual's ability to

maintain balance while standing. As the disease progresses, the individual has difficulty

managing their activities of daily life, experience postural instability, have an increased risk of


falls, and have a dysfunctional gait (Li et al., 2012). Li et al., (2012), conducted a study to

examine if tai chi would improve postural stability in PD patients. 195 patients, ages 40-85 with

stage 1-4 on the Hoehn and Yahr staging scale were divided into groups and received either tai

chi, stretching, or resistance-training (Li et al., 2012). Primary outcomes included improvement

in the limits-of-stability test from baseline. The secondary outcomes were measured by using the

Unified PD Rating Scale (UPDRS) and included measuring gait and strength, functional-reach,

and times up and go tests. Falls were also included as part of the secondary outcomes (Li et al.,

2012).

The study concluded that the tai chi training improved postural stability, reduced the

incidence of falls, increased gait speed, and stride length. Tai chi also appears to reduced

dyskinesia (Li et al., 2012). Participants who received the tai chi training performed consistently

better in maximum excursion and directional control in comparison to the stretching and

resistance-training groups. The tai chi participants also performed better in the secondary

outcomes and falls than the stretching group. Stride length and functional reach were performed

better by the tai chi group participants when compared with the resistance-training group, but did

not lower the incidence of falls when compared to the resistance-training group (Li et al., 2012).

Li et al., (2012), also determined that improvements after tai chi training were maintained at

three months after training.

Vivas, Arias, & Cudeino (2011), also conducted a study on the effects physical therapy

has on PD. The authors examined the effects of land and aquatic therapy on postural stability

and self-movement in PD. Eleven men and women with an average age of 67 received similar

exercises through land or aquatic therapy (Vivas, Arias, & Cudeino, 2011).


Evaluations were completed when patients were on off-dosing of their medications.

Functional Reach Test, Berg Balance Scale, gait, Timed Up and Go test, and the Unified PD

Rating Scale were the main evaluation tools utilized by Vivas, Arias, and Cudeino (2011). This

small study concluded that the aquatic therapy was more effective on postural stability than the

land based therapy in patients with PD (Vivas, Arias, & Cudeino, 2011).

Tomilinson et al., (2012) completed a meta-analysis, which reviewed the use of

physiotherapy intervention in the treatment of PD. After reviewing 39 randomized controlled

trials, the researchers concluded that the studies reported a benefit of physiotherapy for gait

speed, two or six minute walking test, freezing of gait questionnaire, times up and go test,

functional reach test, Berg balance scale, and UPDRS. However, physiotherapy did not appear

to benefit patient rated quality of life (Tomilinson et al., 2012).

The researchers determined physiotherapy has short term benefits in the treatment of PD.

The studies demonstrated that multiple forms of physiotherapy are used in the treatment of PD,

with there being little difference in effect between the different types of physiotherapy

(Tomilinson et al., 2012). The results of the meta-analysis conducted by Tomilinson et al.,

(2012), supports the experimental results of Li et al., (2012) and Vivas, Arias, & Cudeiro (2011),

that tai chi and aquatic therapy, both forms of physiotherapy are beneficial improvements in

motor symptoms of PD.

Surgical treatment. The surgical procedure of choice for those with advanced PD is

deep-brain stimulation. Follett et al., (2010) and Schuepbach et al., (2013) conducted studies

examining the effects of deep brain stimulation in the patients with PD.

Follett et al., (2010), randomly assigned 299 PD patients to undergo pallidal or

subthalamic stimulation and compared 24 month outcomes. Motor function was the primary


motor function assessed on the UPDRS part III, when patients were not receiving anti-parkinson

pharmacotherapy, but receiving stimulation. Self-reported function, quality of life,

neurocognitive function, and adverse events were secondary outcomes measured in the study

(Follett et al., 2010).

Results of the study conducted by Follett et al., (2010) demonstrated that there was not a

significant difference between pallidal and subthalamic stimulation in motor function, self-

reported function, or adverse events. Those undergoing subthalamic stimulation required

dogaminergic agents at a lower dose than the PD patients undergoing pallidal stimulation (Follett

et al., 2010). The visuomotor component of processing speed was found to have declined more

after subthalamic stimulation when compared to pallidal stimulation. Levels of depression

improved after pallidal stimulation, however, there was a worsening of depression following

subthalamic stimulation (Follett et al., 2010)

Schuepbach et al., (2013), conducted a two year study, which randomly assigned patients

with PD with early motor complications to receive neurostimulation in addition to medical

therapy or only medical therapy. This research study concluded that subthalamic stimulation in

PD patients was superior to medical therapy in motor disability, activities of daily living, motor

complications caused by levodopa, and time with good mobility and no dyskinesia (Schuepbach,

et al., 2013). Schuepbach et al., (2013), found that although subthalamic stimulation was

superior to medical therapy, there is a greater risk of adverse events related to the surgical

procedure than just medical therapy, but there is a risk of adverse events for medical therapy as

well.

Pharmacological treatment.Medications are available to help in the treatment of motor

symptoms related to PD, however, even with the availability of these medications, motor


fluctuations remain common for those with advanced PD (Hauser et al., 2013). Hauser et al.,

(2013), conducted a phase 3, double-blind, randomized trial comparing immediate and extended

release carbidopa-levodopa in PD patients who scored a 1-4 on the Hoehn and Yahr disability

scale. Participants must also have been diagnosed with PD after the age of 30, taking levodopa

daily at least four times a day at a dosage of at least 400 mg daily, and experiencing 2.5 hours of

off time a day, and could be taking additional Parkinson's medication if the dosage was stable

(Hauser et al., 2013).

Hauser et al., (2013), concluded that the extended-release carbidopa-levodopa patients

experienced a greater reduction in off-time than those patients who received the immediate-

release medication (Hauser et al., 2013). The extended-release carbidopa-levodopa may be

useful in PD patients with motor fluctuations and reduce dosing frequency, but there are also

downfalls to the extended-release form of carbidopa-levodopa. Extended-release carbidopa-

levodopa have a longer time between when the medication is started, a decrease in motor

fluctuations is noticed by the patient, increased dyskinesia, and there is less predictability of

response in comparison to immediate-release carbidopa-levodopa (Hauser, et al., 2013).

There may be a complex pharmacotherapy schedule that a PD patient may have to follow

to control their symptoms. Lack of adherence to complex dosing schedules leads to less

effective control of PD symptoms (Schapria et al., 2013). Hauser et al., (2013), examined the

use of extended versus immedicate release carbidopa-levodopa in the treatment of PD and

Schapria et al., (2013) examined patient preference of once a day or three time a day (tid) dosing

of pramipexole. Results of the Hauser et al., (2013) and Schapria et al., (2013) may help

improve compliance of a complex medication schedule for PD.


Schiapria et al., (2013) determined from 374 survey responders, that early and advanced

PD patients preferred the once daily dosing versus tid dosing of pramipexole. However, this

study only examined patient preference in the number of daily doses, not the efficacy of

treatment (Schiapria et al., 2013).

Catalan et al., (2013) conducted a study examining levodopa in a different form than that

in the study conducted by Hauser et al., (2013). Catalan et al., (2013) assessed the effect jejunal

levodopa infusion had on advanced stage PD patient's motor complications, severe impulsivity,

and dopamine dysregulation syndrome (DDS), which were not controlled by oral medications.

Patients were given the levodopa infusion for 15 hours a day and reassessed at 25 (+/- 9 weeks).

Catalan et al., (2013), found that off-periods and dyskinesias decreased with the levodopa

infusion compared to baseline. All patients experienced a near complete resolution of symptoms

of DDS and impulse control behaviors with the levodopa infusion therapy (Catalan et al, 2013).

Non-motor Symptoms

Troeung, Egan, and Gasson (2013) conducted a meta-analysis of randomized placebo

trials for PD patients with depression and/or anxiety. Two trials found that non-pharmacological

treatment had a significant effect on depression in patients with PD. However, Troeung, Egan,

and Gasson (2013), found that the studies they reviewed regarding pharmacological treatment of

depression and/or anxiety improved symptoms, but the results were found to be non-significant.

Dementia is a complication that PD patients may face during the course of the disease.

Rivastigmine has been approved in the United States for the treatment of PD dementia (PDD)

and Alzheimer's disease. Impaired executive function, core symptoms of PDD, is part of the

cognitive change that occurred with PD (Schmitt, Farlow, Meng, Tekin, & Olin, 2010).


Schmitt et al., (2010), conducted a randomized controlled study where 541 patients

received rivastigmine or a placebo treatment. Those who received the rivastigmine treatment

experienced significant improvements on the Letter Fluency test, Card Sorting, and had fewer

self-corrected errors on the Color-word Interface, which were the assessment tools utilized to

evaluate each participant. The results of this study indicate that rivastigmine may be beneficial

in individuals with PDD (Schmitt el al., 2010).

Study Limitations

A majority of the studies conducted regarding the treatment of motor and non-motor

symptoms of PD have small sample sizes and have short follow-up time frames (Tomlinson et

al., 2012). In this literature review, the largest sample population was from the study conducted

by Schmitt et al. (2010), who were recruited from multiple countries around the world. The

studies utilized in this literature review also reflects the short follow-up time frames. The study

conducted by Follett et al. (2010), examined pallidal stimulation versus subthalamic stimulation

in the treatment of motor symptoms had a follow-up time frame of two years, which was the

longest follow-up time of this literature review.

Gaps in the Literature

The majority of patients seen in medical offices have multiple serious illnesses. The

majority of studies exclude individuals who have serious medical illnesses in addition to PD,

which makes it difficult to apply research results to patients who have serious comorbidities

(MetaWork Inc. Evidence-base Practice Center, 2003). Research studies should also include

participants of different races, ethnic groups, and ages because the results would then not be

limited to a small population of individuals with PD (MetaWork Inc. Evidence-base Practice

Center, 2003). The research studies included in this literature review, which included Li et al.,


(2012), Vivas, Arias, & Cudeino (2011), Tomilinson et al., 2012, Follett et al., (2010), & Hauser

et al., (2013), support these gaps in the literature through their limited age ranges, lack inclusion

of different minorities, and not including individuals who have chronic illnesses in addition to

PD.

Family members are an important aspect in managing the health of PD patients. The

perception of the caregiver should be included in studies as this may play a role in the

management of care (MetaWork Inc. Evidence-base Practice Center, 2003).

Troeung, Egan, and Gasson (2013) found that there is limited research utilizing

controlled trials that examine the use of pharmacotherapy and non-pharmacological treatment of

depression and anxiety in PD patients. The lack of research studies limits the evidence to

support the use of a specific treatment in PD patients with depression and/or anxiety (Troeung,

Egan, & Gasson, 2013).

Conclusion

PD is the second most common neurodegenerative disease in the world (Haahr,

Kirkevold, Hall, & Ostergaard, 2011) and affects between one to two percent of the population

over age 65 (Casey, 2013). Progression of the disease, and responses to treatments, vary from

case to case requiring a close relationship between patients, families, and their health care

providers (Osborne, 2009). Providing care for patients with PD requires a detailed

understanding of the course of illness, treatment options, and recent developments in research

(Casey, 2013). Living with PD can be unpredictable, and patients experience a loss of physical,

psychological, and social characteristics (Haahr, Kirkevold, Hall, & Ostergaard, 2011).

This literature review revealed optimal PD management converges non-pharmacological,

pharmacological, and surgical interventions to best support the patient's overall well-being. As a


cure for PD is not yet available, maintenance of the patient's symptoms and quality of life is the

target for the APRN's plan of care. Further research about treatment options is necessary as PD

symptoms can impact every aspect of a patient's life in an unpredictable and progressive manner.

APRNs can provide PD care by means of personalized attention to patients and

caregivers as the disease progresses. A multidisciplinary team approach offering integrated care

is important for care management (Lindop, 2012). The APRN's role is to provide close clinical

monitoring and treatment adjustment while bestowing personal support to patients and families.


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Appendix A

Studies Focus Subjects Population Age Method Findings

Catalan, et al., (2013)

Use of levodopa infusion in advanced stage Parkinson's disease patients in the treatment of impulsivity and dopamine dysregulation syndrome (DDS) that were not controlled with oral medication

N = 24 Patient's with severe Parkinson's disease, disabling motor fluctuations and dyskinesia

Average age 67.9 years

Quazi-experimental

Levodopa infusion decreased the off-periods and dyskinesias decreased when compared to baseline in advanced stage Parkinson's disease patients. All patients experienced a near complete resolution of symptoms of DDS and impulse control behaviors with the levodopa infusion therapy.

Follett et al., (2010)

Pallidal stimulation versus subthalamic stimulation in patients with advanced Parkinson's disease

N =299pallidal stimulation (152 patients)Subthalamic stimulation (147 patients)

Patient's with Parkinson's disease in stage 2 or higher on the Hoehn and Yahr disability scale, had a response to levodopa, had persistent and disabling symptoms despite optimal medical treatment, poor motor function or symptom control for 3 out of 24 hours, and having been receiving medical treatment but

At least 21 years

Randomized Controlled TrialQuantitative experimental

There was no significant difference in change in motor function between pallidal stimulation and subthalamic stimulation. Of the secondary outcomes there was no statistical difference between the surgical procedures in self-reported function and adverse events. Lower doses of dopamine were required and a decline in a component of processing speed was observed in


having no changes in therapy in the last month

those who undergoing subthalamic stimulation. Depression worsened following subthalamic stimulation and improved following pallidal stimulation.

Hauser et al., (2013)

Comparing immediate-release and extended-release carbidopa-levodopa on motor fluctuations in Parkinson's patients

N = 393(201 extended-release)(192 immediate-release)

Parkinson's disagnosis after age of 30, stage 1-4 on the Hoehn and Yahr disability scale, mini-mental status exam score of 26, stable regimen of immediate-release levodopa, average of 2.5 hrs off time per day.

No age provided

Randomized Controlled double-blind trialQuantitative experimental

Etended-release carbidopa-levodopa patients experienced a greater reduction in off-time than those patients who received the immediate-release medication. The extended-release medication also reduces the dosing frequency of levodopa.

Li et al., (2012)

Comparing tai chi, resistance training and stretching to improve postural stability.

N = 195 Parkinson's disease patients in stage 1-4 on the Hoehn and Yahr staging scale, at least one score of 2 or more in the motor section of the Unified Parkinson's Disease Rating Scale, stable medication use, able to stand unaided or walk with or without assistive device.

40-85 years


Tai chi appeared to improve maximum excursion and directional control in comparison with resistance-training and stretching. The tai chi group out performed the stretching group in all secondary outcomes and lowered the incidence of falls when compared to the stretching group. The tai chi group also preformed better than the resistance-training


group in stride length and functional gait, but did not lower the incidence of falls when compared to the resistance-training group.

Schapira, et al., (2013)

Patient preference of once daily versus three times a day dosing of pramipexole in early or advanced Parkinson's disease

N = 374 (number who completed trail and survey)

Parkinson's disease patients, initially at stage 1-3 on the Hoehn and Yahr staging scale, diagnosed within in the last 5 years, diagnosed at or after the age of 30

No age given

Quazi-experimental

Both early and advanced stage Pakinson's patients found that once a day dosing was more convenient than three times a day dosing. This study only looked at convenience and not treatment efficacy.

Schmitt et al., (2010)

Rivastigmine versus placebo treatment for dementia in Parkinson's patients

N = 541 Individuals with Parkinson's disease dementia

Average age 72.7 years


Rivastigmine was found to be superior than the placebo on the executive function tests, which evaluates planning, problem solving, and flexibility of thinking those patients with dementia related to Parkinson's disease.

Schuepbach et al., (2013)

Use of subthalamic stimulation and medical therapy or medical therapy alone in the treatment of early motor complications in Parkinson's disease

N = 251 Parkinson's disease patient age 18-60; have had Parkinson's for at least 4 years; rating of below stage 3 on the Hoehn and Yahr staging scale when on medication; improving motor signs on dopaminergic

Average age of 52(Age 18-60)


Subthalamic stimulation in was superior to medical therapy in motor disability, activities of daily living, motor complications caused by levodopa, and time with good mobility and no dyskinesia in Parkinson's patients. There is a greater risk of adverse


medications; fluctuations or dyskinesia for 3 years of less; mild to moderate impairment in social and occupation functioning, or score of more than 6 on the UPDRS II for activities of daily living

events with subthalamic stimulation than medical therapy alone.

Tomlinson et al., (2012)

Analysis of different types of physiotherapy in the treatment of Parkinson's disease

N = 39 Randomized controlled trials comparing physiotherapy with no intervention

No age given

Meta-analysis

Physiotherapy has short term benefits in the treatment of Parkinson's disease. The studies demonstrated that multiple forms of physiotherapy are used in the treatment of Parkinson's disease. There is little difference in the effects of the different types of physiotherapy.

Troeung, Egan, & Gasson (2013)

Meta-analysis of placebo-controlled randomized trials in treating depression and/or anxiety in Parkinson's patients

N = 9 studies

Randomized placebo-controlled trials on treatment of depression and anxiety in Parkinson's patients

No age given

Meta-analysis

Two trials found that non-pharmacological treatment had a significant effect on depression in patients with Parkinson's disease. The studies reviewed regarding pharmacological treatment of depression and/or anxiety improved symptoms, but the results were found


to be non-significant.

Vivas, Arias, & Cudeiro (2011)

Comparing aquatic and land based therapy on postural stability and self-movement in Parkinson's patients

N = 11 Parkinson's disease patients in stages 2-3 on the Hoehn and Yahr staging scale while in off-staging medication phase, and no dementia,

Average age 67 plus or minus 5.5 years


Both the land and aquatic therapy groups demonstrated improvements on the Functional Reach Test, while only the aquatic group showed improvements in the Berg Balance Scale and the Unified Parkinson's Disease Rating Scale. The aquatic group demonstrated a significantly larger improvement in postural stability after therapy than the land based treatment group.

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Parkinson's Disease Treatment - katiescanlon.weebly.comkatiescanlon.weebly.com/.../6/48166929/...scanlon.docx · Web viewLi et al., (2012), conducted a study to examine if tai chi