rasagaline for treatment of parkinson's disease

8/12/2019 Rasagaline for Treatment of Parkinson's Disease

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Rasagiline for the Treatment of Parkinsons DiseaseI. Etiology1

1. Idiopathic PD

2. Secondary Parkinsonism: drug induced, environmental toxicities, result of CNS

infection, genetic

II. Clinical Presentation1

1. Four central motor features: resting tremor, bradykinesia, rigidity, postural instability

2. Non-motor symptoms

i. Neuropsychiatric: Depression, anxiety, dementia, psychosis, impulse control

disorders (ICDs)

ii. Sleep disorders: Insomnia, sleep apnea, daytime somnolence

iii. Other: dysphagia, choking, hypersalivation

III. Diagnosis2

1. Gold Standard- presence of Lewy bodies at autopsy

2. Criteria- at least 2 of the following: Tremor, bradykinesia, rigidity

3. Diagnosis of exclusion (drug induced, metabolic disorders, trauma, structuralabnormalities of the CNS)

IV. Pathophysiology1, 3

1. Dopamine: inhibitory and excitatory neurotransmitter, depending on the type of

dopaminergic receptor it binds to

2. Parkinsons Disease

i. loss of dopaminergic neurons leading to depletion of dopamine

V. Assessment /Monitoring1,3 .

1. UPDRS

i. Allows for an overall measure of disability as well as individual subscoresii. Includes four major parts: mentation, behavior, mood, ADL, motor

examination, complications of therapy

iii. Allows the assessment of worsening or improvement of PD over time

(worsening of symptoms increases score, improvement of symptoms

decreases score)

2. Modified Hoehn & Yahr Staging Scale - assesses motor skills

3. Schwab & England Activities of Daily Living - assesses ADL

VI. Treatment Guidelines3

1. Pharmacologic includes: MAO-B inhibitors, Dopamine agonists, Amantadine,

Carbidopa/Levodopa, COMT inhibitors

2. Non Pharmacologic: Environmental, diet, exercise, support

VII. Pharmacology of Rasagiline3

i. MAO-I Type B inhibitor

ii. same class as selegiline BUT does not form amphetamine metabolites

VIII. Clinical Trials4

1. The TEMPO Study


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i. objective to evaluate the safety and efficacy of the selective monoamine

oxidase type B inhibitor rasagiline

ii. design - multicenter, randomized, placebo-controlled, double blind,

parallel groups

iii. methodology: 3 parallel groups: placebo, 1 mg/d rasagaline, and 2 mg/d

rasagaline

iv. Eligibility:

a. Inclusion: Patients over 35 years with at least 2 cardinal signs ofPD and whosedisease severity was not greater than Hoehn andYahr stage III.

b. Exclusion: (1) atypical or secondaryparkinsonism, (2) unstablemedical problems, including CHF of NYHA class II or greater,

(3) psychiatric problems that compromised the ability of the

subject to give informed consent, (4) a MMSE score of 23 or

less, or (5) clinically significant depression.Subjects could betreated with anticholinergic medications,but other

antiparkinsonian medications, including levodopa,dopamineagonists, selegiline, or amantadine, were not permitted.

Antidepressants (with the exception of amitriptyline,paroxetine,sertraline, fluvoxamine, or trazodone) and

sympathomimeticswere not permitted.

v. Endpoints:a. Primary: Change in UPDRS score between baseline and week

26.b. Secondary: changes subscales of theUPDRS, as well as

symptom-based

subscores (tremor,rigidity,bradykinesia, and

postural instability/gait

disorder); changes in theHoehn andYahr stage,the Schwab-England ADL

scale, Beck Depression

Inventoryscore, timedmotor tests, and theParkinson's Disease

Qualityof Life(PDQUALIF) scale.

vi. Results of primary andsecondary endpoints: See

table 1

vii. Conclusions:a. Rasagiline is an effective

therapy for patients with early PD

Table 1.


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3. Safety: Rasagilie was found to be associated with weight loss, vomiting, anorexia,

imbalance, headache, dizziness and asthenia.

4. Use of rasagaline as both monotherapy and adjunct therapy is very beneficial to the

therapeutic treatments of PD

1. Weintraub, D, Comella, C, Horn, S. Pathophysiologu, Symptoms, Burden, Diagnosis, and

Assessment. The American Journal of Managed Care. 2008 Mar; 14 : S40-S48.

2. Rao, S, Hofmann, L, Shakil, A. Parkinsons Diease: Diagnosis and Treatment. American

Family Physician. 2006 Dec; 74 : 2046-54

3. Chen, J, Merlin, V, Swope, D. Parkinsons Disease. In: DiPiro JT et al. Pharmacotherapy. 6th

ed. New York : McGraw-Hill Medical Publishing, 2005. 977- 988

4. Parkinson Study Group. Archives of Neurololgy. 2002; 59: 1937-1943.

Horstink M,Tolosa E,Bonuccelli U,Deuschl G,Friedman A,Kanovsky Pet.

Al. Review of the therapeutic management of Parkinson's disease.Report of a joint task force of the European Federation ofNeurological Societies and the Movement Disorder Society-European Section. Part I: early (uncomplicated) Parkinson'sdisease.Eur J Neurol.2006 Nov;13(11):1170-85.

Horstink M,Tolosa E,Bonuccelli U,Deuschl G,Friedman A,Kanovsky Pet.

Al. Review of the therapeutic management of Parkinson's disease.Report of a joint task force of the European Federation of

Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson'sdisease.Eur J Neurol.2006 Nov;13(11):1186-202.

Lexi-Drugs Online. Lexi-Comp Online, Lexi-Comp Inc. Hudson, OH. Available at:http://online.lexi.com/crlsql/servlet/crlonline Accessed 10/10/08.
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rasagaline for treatment of parkinson's disease

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