Treatment of Motor Symptoms of Parkinson's Disease

Treatment of Motor Symptoms in Early Stage PD

If the patient does not experience any limitations, it is possible to wait with therapy and only recommend lifestyle measures (especially physiotherapy). The previously common initiation of treatment with selegiline (a monoamine oxidase B inhibitor) is no longer recommended due to its unproven neuroprotective effect; another MAO-B inhibitor, rasagiline, is not available in the Czech Republic.

In clinical practice, it is more common for the patient to already report functional limitations at the time of PD diagnosis, which requires the initiation of symptomatic therapy.

The most effective drug to influence motor symptoms is levodopa, but its use is associated with the development of motor complications – fluctuations in mobility status and involuntary movements (dyskinesias), which typically appear about 5 years after starting treatment.

For cognitively intact patients younger than 65 years, therapy is initiated with a gradual titration (approximately 6-8 weeks) of dopamine agonists (DA) – pramipexole, ropinirole, or rotigotine. An exception is a situation requiring a rapid onset of medication effect – for example, the threat of job loss in a young patient.

Levodopa treatment is initiated in older patients or those with cognitive deficits, who have a higher risk of developing psychotic complications. Levodopa titration also needs to be slow, and in the early stage, dosing is usually divided into 3-4 doses per day. Common side effects when administering dopaminergic therapy are vegetative symptoms – mainly nausea and orthostatic problems. As prevention, we administer the peripheral dopaminergic receptor blocker domperidone (contraindicated in patients with prolonged QT interval).

Treatment of Motor Complications in the Moderate Stage PD

In this stage, motor complications develop. The shortening of dose effect (wearing off) and motor fluctuations (alternating on/off states) are addressed by adding a catechol-O-methyltransferase (COMT) inhibitor – entacapone; later on, also by shortening the interval between doses.

Involuntary movements (dyskinesias) can also be mitigated by shortening the dosing interval while administering lower individual doses of levodopa.

Amantadine is appropriate for influencing dyskinesias and walking disorders during the on state in patients with a low risk of developing psychotic complications.

Treatment of Motor Complications in Advanced Stage PD

In the advanced stage of PD, there is a combination of native manifestations and increasing motor and non-motor complications. In this phase, most patients are treated with a combination of levodopa with COMT inhibitors, optionally DA and amantadine. In the event of developing psychotic complications or cognitive deficits, it is necessary to reduce or completely withdraw amantadine and DA.

Treatment of Motor Complications with Interventional Methods

When pharmacotherapy is insufficient, deep brain stimulation (DBS), levodopa administered via enteral infusion (DuoDopa), or apomorphine treatment by subcutaneous infusion are therapeutic options for patients in the moderate and advanced stage of the disease, who meet strict indication criteria.

Conclusion

Effective treatment of Parkinson's disease must be individually tailored to each patient. The therapy of motor symptoms at all stages of the disease includes not only pharmacological treatment but also physiotherapy and speech therapy to influence speech and swallowing disorders.

MUDr. Olga Ulmanová, Ph.D.
Center for Extrapyramidal Disorders, 1st Faculty of Medicine, Charles University and General University Hospital in Prague

References:
Jankovic J., Tan E. K. Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry 2020; 91: 795–808, doi: 10.1136/jnnp-2019-322338.