• 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, 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
• 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
• 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
  • Pergolide is useful for initial therapy of Parkinson’s disease
  • Pramipexole is an effective treatment of motor complications and prevention/delay of motor symptoms
  • Ropinirole may be considered in early Parkinson’s disease and in patients who develop motor fluctuations
  • 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
• 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