Parkinson's%20disease%20-and-%20parkinson's%20disease%20dementia Treatment

• Choice of medication depends on the following factors: Stage of disease, relative effectiveness and adverse effect profile of the drugs, clinician experience, patient’s comorbidities, degree of functional disability, level of physical activity and productivity, employment status and preference
• Improvements in drug efficacy and symptom control may be measured in clinical trials using rating scales (eg Hoehn & Yahr scale, Schwab & England scale, Unified Parkinson’s Disease Rating Scale)

Treatment Goals

• Alleviate motor and nonmotor symptoms that interfere with patient’s daily activities
• Limit complications as disease progresses
• Slow down or modify disease progression
• Motor symptoms are relieved by supplementation of cerebral dopamine
• Nonmotor dysfunction is relieved by symptomatic treatment

Dopamine Precursor

Levodopa

• Remains the most effective treatment for Parkinson’s disease symptoms
• Preferred initial therapy in Parkinson’s disease patients with cognitive impairment, with atypical presentation, or in the elderly
• Recommended as the initial therapy for patients with early Parkinson's disease who seek treatment for motor symptoms
  • Should be initially prescribed as immediate-release Levodopa and with the lowest effective dose to minimize adverse effects
• Studies have shown that Levodopa demonstrates greater improvement in mobility compared to monoamine oxidase B inhibitors and dopamine agonists when given early in the disease
  • More likely to induce dyskinesia compared to dopamine agonists but the prevalence of severe or disabling dyskinesia is low within a 5-year period
• Acts as a dopamine precursor that is converted into dopamine in the brain
  • Levodopa rapidly decarboxylates peripherally so that little unchanged drug is available to cross the blood-brain barrier
  • Always administer in combination with a peripheral dopa-decarboxylase inhibitor (Carbidopa) to increase the amount of Levodopa entering the brain. Therefore, less Levodopa needs to be administered, ensuring more rapid response to therapy and less peripheral side effects
• Reduces debilitating symptoms
  • Most effective in alleviating bradykinesia and rigidity
  • Incidence of dyskinesia & “on-off” fluctuation with long-term use is common
  • Behavioral disturbances (eg hypersexuality, excessive gambling and shopping, compulsive eating) have occurred with long-term use

Dopamine Agonists

• Ergot-derived: Bromocriptine, Cabergoline, Lisuride, Pergolide
  Non-ergot derived: Apomorphine, Piribedil, Pramipexole, Ropinirole, Rotigotine
• Recommended as monotherapy or as an adjunctive therapy to Levodopa
• Effective in the treatment of patients with early Parkinson’s disease and motor symptoms
  • May prescribe dopamine agonists as the initial treatment in early Parkinson's disease patients <60 years who are at higher risk of developing dyskinesia
  • Should be prescribed the lowest effective dose possible to provide therapeutic benefit
  • Systematic screening of patients for risk factors for adverse effects associated with medication use or disease progression by administering questionnaires (eg The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease [QUIP], Epworth Sleepiness Scale [ESS])
• Not recommended for patients w/ early Parkinson's disease who are at higher risk of medication-related adverse effects, >70years old, history of impulse control disorders and preexisting cognitive impairment, excessive daytime sleepiness or hallucinations
• When dopamine agonist treatment is to be discontinued due to adverse effects, it is recommended to monitor for symptoms of dopamine agonist withdrawal syndrome (DAWS) and to gradually decrease the dosage to minimize symptoms
• Act to stimulate dopamine receptors
• Less likely to have motor fluctuations in later stages of the disease when therapy is started in early disease
  • Less effective than Levodopa in controlling rigidity and bradykinesia, but less likely to cause dyskinesia
  • Piribedil, Pramipexole and Ropinirole do not stimulate serotonin receptors, thus cause less side effects than other dopamine agonists
  • Apomorphine is used to stabilize patients experiencing refractory motor fluctuations, but subcutaneous injection is suitable for capable and motivated patients only
  • Bromocriptine may be used in early and late disease
  • Cabergoline is found to be clinically useful in preventing or delaying the onset of motor fluctuations
  • Pergolide is useful for initial therapy of Parkinson’s disease
  • Pramipexole is an effective treatment of motor complications, in preventing/delaying motor symptoms and delaying dyskinesia
  • Ropinirole may be considered in early Parkinson’s disease, in patients who develop motor fluctuations and for delaying dyskinesia
  • Rotigotine may be used in idiopathic Parkinson’s disease as monotherapy or in combination with Levodopa
  • Behavioral disturbances (eg hypersexuality, excessive gambling and shopping, compulsive eating) have occurred with long-term use

Monoamine Oxidase B Inhibitors

• Eg Selegiline, Rasagiline, Safinamide
• Selegiline in early Parkinson’s disease was shown to postpone the need for dopaminergic treatment by several months
• Associated with mild to moderate benefits in symptomatic control of Parkinson’s disease
• Recommended as monotherapy or as an adjunct to Levodopa
  • May be associated with higher risk of discontinuation due to adverse effects
• For patients with motor fluctuations, Rasagiline is recommended to reduce off time
• May be used initially for mild symptomatic benefit prior to the start of dopaminergic therapy
  • Neuroprotective benefit has yet to be proven

• Acts to inhibit activity of enzyme monoamine oxidase B irreversibly, preventing the metabolism of naturally occurring dopamine and dopamine formed from Levodopa
• The action of Levodopa is prolonged by the addition of Selegiline; therefore, Levodopa’s “wearing off” fluctuations are decreased
  • May provide slight improvement in symptoms
  • Has antioxidant effects, but a neuroprotective benefit has yet to be proven
• Safinamide has been approved by US FDA as an add-on treatment to Levodopa/Carbidopa in patients with Parkinson’s disease having off time

• Eg Entacapone and Tolcapone
• Recommended as adjuncts to Levodopa and Carbidopa drug combination
• For patients with motor fluctuations, Entacapone is recommended to reduce off time
• Tolcapone has limited use due to risk of hepatotoxicity, use only when other adjunctive treatment fails
• Selective potent, peripheral and to a lesser extent central, reversible inhibitor of catechol-O-methyltransferase, which prevents the metabolism of naturally occurring dopamine and dopamine formed from Levodopa
  • Hence, more Levodopa reaches the central nervous system and is converted to dopamine

• May decrease motor fluctuations when administered as adjuncts to Levodopa
  • A lower effective dose of Levodopa is required, thus reducing side effects
  • Trials are underway to assess if they reduce the progression of motor complications

Anticholinergics

• Eg Benztropine, Benzhexol (Trihexyphenidyl), Biperiden, Orphenadrine, Procyclidine
• Recommended as monotherapy or as adjuncts to Levodopa
• May be considered for initial therapy prior to dopaminergic therapy in younger patients if tremor is predominant
• Act by inhibiting the effects of acetylcholine in the brain
• Relieve symptoms of tremor in Parkinson's disease but has little effect on bradykinesia
  • Benztropine and Trihexyphenidyl are most effective in patients with more prominent tremor than rigidity symptoms
  • Only 50% of patients respond to treatment with 30% improvement
  • Anticholinergic side effects limit their use

Others

Amantadine

• Recommended as monotherapy or as an adjunctive therapy to an anticholinergic or Levodopa
• A weak dopamine agonist with some antimuscarinic activity
• Manages Parkinson's disease in early stages when symptoms are mild
  • Relieves symptoms of bradykinesia, rigidity and tremor; may also improve dyskinesia
  • Effects wear off after several months of treatment, effectiveness may return after brief withdrawal

Apomorphine

• Intermittent Apomorphine injections may be used to reduce off time in people with Parkinson's disease with severe motor complications
• Continuous subcutaneous infusions of Apomorphine may be used to reduce off time and dyskinesia in people with Parkinson's disease with severe motor complications
• Its initiation should be restricted to expert units with facilities for appropriate monitoring

Supportive Treatment

• Support groups
  • Offer psychosocial help to patient and family

• Psychiatric counseling
  • Counsel patient and families on how to cope with the illness

• Legal counseling
• Financial counseling
• Occupational counseling
  • Counsel on the adaptations that may be needed to ensure productivity at work

• Slowness of gait, poor postural reflexes, involuntary movements and orthostatic hypotension contribute to falls
• Prevent falls by wearing leather-soled shoes, removing throw rugs at home, adjust pharmacological therapy if required

Management of Sleep Disturbances

• Sleep disturbances occur due to the proximity of substantia nigra to sleep and arousal centers in the brain stem
• Manage sleep disturbances by medication adjustment, dietary modifications, sleep hygiene practices or referral to physician with specialized training in sleep physiology

Speech Therapy

• Help correct pharyngeal musculature impairment that may cause speech and swallowing difficulty
• May improve volume of speech and swallowing when administered with oral Levodopa