Parkinson's%20disease%20-and-%20parkinson's%20disease%20dementia Treatment
Principles of Therapy
- 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
Pharmacotherapy
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
- 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
- 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
Non-Pharmacological Therapy
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
Fall Prevention
- 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