Parkinson’s Disease: Drug Therapy

Therapy goals

  • Improvement of mobility
  • Improvement/mitigation of tremor
  • Improvement of the psychological and vegetative symptoms.

Therapy recommendations

Therapy recommendations of the German Society of Neurology.

Patient Active ingredient groups Active ingredients
<70 years,no significant comorbidities First choice agent Dopamine receptor agonists Piribedil pramipexole ropinirole
Non-ergoline dopamine agonists Rotigotine
Second choice agent Ergoline dopamine agonists Bromocriptine cabergoline α-dihydroergocriptine lisuride pergolide
Alternative for mild symptoms MAO inhibitor (monoamine oxidase inhibitor). RasagilineSelegiline
N-methyl-D-aspartate recptor antagonists (NMDA antagonists). Amantadine* *
> 70 yearsMultimorbidity Means of first choice Levodopa L-dopa*
Alternatively for mild symptoms MAO inhibitor (monoamine oxidase inhibitor). RasagilineSelegiline
N-methyl-D-aspartate recptor antagonists (NMDA antagonists). Amantadine

* The older the PD patient, the lower the risk of dyskinesia with L-dopa. * * Amantadine may be considered as second-line therapy for patients in early stages of idiopathic Parkinson’s syndrome IPS). (Expert Consensus)

Further references

  • MAO-B inhibitors, dopamine agonists, or levodopa should be used in the symptomatic therapy of early stage idiopathic Parkinson’s disease (IPS). A (1++)The selection of the different substance classes should take into account the different effect sizes in terms of efficacy, side effects, age of the patient, comorbidities, psycho-social requirement profile. Expert consensus
  • L-dopa:
    • Has the strongest effect on akinesia (high-grade lack of movement to immobility), followed by rigor (rigidity; muscle stiffness) > tremor (shaking)
    • First-line agent in elderly patients (> 70th LJ) or in multimorbid patients.
    • Must always be combined with peripheral decarboxylase inhibitors (benserazide or carbidopa) to prevent levodopa from being converted to dopamine in the intestine immediately after administration
    • Combination with dopamine agonists recommended.
    • Toxicity: the LEAP study showed that early therapy with L-dopa does not carry additional risks.
  • Dopamine agonists (see above ):
    • Act most strongly on akinesia, followed by rigor > tremor.
    • Monotherapy is method of first choice in young patients (< 70th LJ) without significant co-morbidities; combination with levodopa recommended if success is unsatisfactory
  • Anticholinergics (biperiden, metixen, trihexyphenidyl): most effective in rigor and tremor; Cave! Not in elderly patients or in cognitively impaired individuals.
  • COMT (catechol-O-methyl transferase) inhibitors: only in combination with L-dopa for “end-of-dose” fluctuations (L-dopa).
  • MAO inhibitors (monoamine oxidase inhibitors): rasagiline, selegiline.
    • Selegiline as a monotherapeutic agent in elderly and multimorbid patients with mild symptoms.
  • N-methyl-D-aspartate recptor antagonists (NMDA antagonists): amantadine.
    • Has the strongest effect on akinesia and rigor.
    • Agent of choice in akinetic crisis
    • First-line monotherapy for mild symptoms in young as well as elderly patients and multimorbidity.
    • Loss of effect after a few months
  • The use of psychotropics (psychoactive substances) in elderly patients is associated with increased mortality (mortality)
  • Beta-blockers may be considered for symptomatic therapy of postoral tremor in selected patients with early idiopathic parkinsonism but should not be first-line agents. (Expert Consensus)
  • When off-phases (phases when the antiparkinsonian drug has no effect) in IPS cannot be adequately controlled with oral medication, subcutaneous apomorphine injections are recommended; alternatively, intrajejunal levodopa/carbidopa infusion.
  • See also under “Further therapy”.

New active ingredients

  • Safinamide; mode of action: dual mechanism of action (MAO-B inhibitor and antiglutamatergic effect); indication: idiopathic Parkinson’s disease (IPS):
    • Only in patients taking L-dopa.
    • Avoiding an increase in L-dopa doses above 400 mg.
    • Mild motor fluctuations
    • Mild dyskinesias
    • Possibly improvement of attention
    • Wearing-Off

Parkinson’s disease and fatigue (tiredness) and anhedonia (inability to feel pleasure and joy)

Guideline recommendations:

Parkinson’s disease and dementia or dementia of Lewy body type (PSYC3)

Guideline recommendations:

PDD and depression

Guideline recommendations:

Parkinson’s disease and hypersalivation

Hypersalivation (sialorrhea or ptyalism; English “drooling”), the involuntary discharge of saliva above the lip margin, occurs in up to 75% of patients with idiopathic PD. In a randomized, double-blind, placebo-controlled study in a cross-over design, 10 patients were studied with incobotulinum toxin (100 units) versus NaCl 0.9%. One injection was given monthly into each of the parotid (20 units) and submandibular (30 units) glandula. Patients were examined monthly: no effect of incobotulinum toxin A on hypersalivation in IPS was demonstrated.

Parkinson’s disease and psychosis

Guideline recommendations:

  • Clozapine should be used to treat psychosis in patients with idiopathic Parkinson’s disease IPS. A (1++)
  • Quetiapine can be used to treat psychosis in patients with IPS. (Expert consensus)
  • Olanzapine should not be used to treat psychosis in patients with IPS. A (1++)
  • In patients with IPS psychosis and concomitant dementia, cholinesterase inhibitors are an alternative. (Expert consensus)

Parkinson’s disease and sleep disorders

Guideline recommendations:

  • Nocturnal akinesia (high-grade lack of movement to immobility) and early morning dystonia (movement disorder manifested by involuntary contraction of muscles) should be treated with transdermal rotigotine or sustained-release ropinirole. (1+)
  • Treatment of insomnia with sleep-through disturbance should be attempted with zopiclone. B (1+)