Medical treatment of Parkinsonism

NICE guidance suggests (1)

First-line treatment (1)

• levodopa should be offered to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life
• for people in the early stages of Parkinson's disease whose motor symptoms do not impact on their quality of life
  • consider a choice of dopamine agonists, levodopa or monoamine oxidase B (MAO-B) inhibitors
  • do not offer ergot-derived dopamine agonists as first-line treatment for Parkinson's disease

Adjuvant treatment of motor symptoms

• if a person with Parkinson's disease has developed dyskinesia and/or motor fluctuations, including medicines 'wearing off', seek advice from a healthcare professional with specialist expertise in Parkinson's disease before modifying therapy
• a choice of dopamine agonists, MAO-B inhibitors or catechol-O-methyl transferase (COMT) inhibitors should be offered as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy, after discussing:
  • person's individual clinical circumstances, for example, their Parkinson's disease symptoms, comorbidities and risks from polypharmacy
  • person's individual lifestyle circumstances, preferences, needs and goals
  • potential benefits and harms of the different drug classes

• in most cases a non-ergot-derived dopamine agonist in most cases, because of the monitoring that is needed with ergot-derived dopamine agonists
  • an ergot-derived dopamine agonist should only be chosesn as an adjunct to levodopa for people with Parkinson's disease:
    • who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy and
    • whose symptoms are not adequately controlled with a non-ergot-derived dopamine agonist
• amantadine should be considered if dyskinesia is not adequately managed by modifying existing therapy

The commonly used drugs in the management of Parkinson's disease are listed below:

• L-dopa:
  • levodopa may be used as a symptomatic treatment for people with early PD (1)
  • first line treatment for most patients
    • offer levodopa to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life (1)
  • usually combined with an inhibitor of peripheral dopa decarboxylase
  • slow-release preparations may reduce side-effects
  • the dose of levodopa should be kept as low as possible to maintain good function in
    order to reduce the development of motor complications (1)
  • a newer preparation of the drug has been licensed for the treatment of severe motor complications - a levedopa gel (Duodopa) used as a continuous infusion directly into the jejunum (2)
    
    
• dopamine receptor (D2) agonists:
  • Dopamine agonists may be used as a symptomatic treatment for people with early PD (1)
  • considered a possible first line treatment (1)
  • in advanced disease used in conjunction with L-dopa to control fluctuations in response and required levadopa dose (2)
  • may be used as monotherapy in early disease - it has been hypothesised that introducing dopamine agonists in the early stages of disease, before L-dopa
    • is useful in controlling the motor symptoms (although less effective than levadopa)
    • is associated with fewer motor complications compared to levadopa (2)
  • there are 2 groups
    • ergot-related - bromocriptine, cabergoline, lisuride and pergolide
    • non-ergot-related - ropinirole, pramipexole and rotigotine (2)
  • non ergot related drugs are used as first line treatment due to the associated risk of severe fibrotic and serosal inflammatory disorders seen with the ergot related preparations (2).
  • if an ergot-derived dopamine agonist is used, the patient should have a minimum of renal function tests, erythrocyte sedimentation rate (ESR) and chest radiograph performed before starting treatment, and annually thereafter (1)
  • ropinirole XL (once-daily) can be used in both the early and advanced disease (2)
    
    
• MAOB (monamine oxidase type B) inhibitors e.g. selegiline, rasagiline:
  • inhibitors may be used as a symptomatic treatment for people with early PD (1)
  • the use of this drug class is controversial
  • may be used in advanced Parkinson's to reduce motor fluctuations (2)
  • considered a possible first-line therapy (1)
    
    
    
• COMT-inhibition: e.g.- entacapone, tolcapone:
  • second line treatment
  • used as an adjunct to L-dopa (increases half life of the drug)
    
    
• anticholinergic agents:
  • occasionally used especially when tremor predominates
  • may be used as a symptomatic treatment typically in young people with early PD and severe tremor
  • should not be drugs of first choice due to limited efficacy and the propensity to cause neuropsychiatric side effects
    
    
• amantadine:
  • response rate is low and tolerance occurs
  • may be used as a treatment for people with early PD but should not be a drug of first choice
• beta blockers
  • may be used in the symptomatic treatment of selected people with postural tremor in PD, but should not be drugs of first choice (1)
    
    
• apomorphine
  • a potent dopamine agonist
  • useful in patients with severe motor complications to decrease 'off' periods and dyskinesia
  • currently two treatment approaches are used
    • in patients with less than six 'off' periods per day - intermittent subcutaneous rescue injections
    • in patients with more frequent episodes - continuous infusion (2)

Reference:

1. NICE (July 2017). Parkinson's disease in adults
2. Turnbull C, Fitzsimmons P. Advances in the treatment of the motor symptoms of Parkinson's disease. J R Coll Physicians Edinb 2009; 39:29-31
3. MeReC Bulletin 1999;10 (10): 37-40.
4. Parkinson's disease Research Group of the United Kingdom. Comparison of therapeutic effects and mortality data of levodopa and levodopa commbined with selegiline in patients with early, mild Parkinson's disease. BMJ 1995; 311: 1602-7.