Are Current Therapies in Late-Stage Parkinson Disease Effective?

Adverse effects such as OFF periods, falls, and tremor were found to be prominent in patients with late stage Parkinson disease (PD), signaling the potential failure of current treatments to consistently and effectively address these symptoms as the disease progresses, according to study findings published in Parkinsonism & Related Disorders.

Although current therapies within PD, such as levodopa and carbidopa, have assisted in managing OFF periods and other adverse symptoms, they have also been shown to lose effectiveness as the disease progresses. In fact, these OFF periods, which are characterized as the recurrence of tremors and motor/nonmotor symptoms, have been shown to occur in 90% of patients with PD (PwP) after 10 years, a stark increase from 40% in PwP after 4 to 6 years of treatment.

Researchers sought to further examine the relation between disease duration and symptom severity, which they note is lacking in the current literature. They examined scores of several factors within the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), such as falls, freezing, and OFF periods. The multicenter study included 692 PwP who met the inclusion criteria of disease duration ≥ 7 years and either Hoehn and Yahr stage ≥ 4 or Schwab and England score of 50 or less.

In the study, PwP exhibited a mean (SD) disease duration of 15.4 years (7.7), mean total MDS-UPDRS score of 82.7 (22.4), mean levodopa equivalence dose of 874.1 (591.1) milligrams per day, and dementia prevalence of 37%.

In examining adverse factors, 82% of patients reported falls, with 16% of those related to freezing, 21% unrelated to freezing, and 45% related and unrelated to freezing. OFF periods were shown to occur in 68% of PwP and were indicated to be present for at least 50% of the day in 13% of patients, with morning dystonia occurring in 35%. Moreover, moderate to severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16%, and tremor by 11%. More adverse effects were also noted:

• Dyskinesias were reported by 45% of patients, but were moderate or severe in only 7%
• Moderate to severe fatigue, constipation, urinary symptoms and nocturia, concentration, and memory problems were encountered by more than half of participants
• Hallucinations or delusions were present in 63% and were moderate to severe in 15%

The researchers noted that the association of overall disability was “strongest for severity of falls/postural instability, bradykinesia, cognitive score, and speech impairment.”

“These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients,” concluded the study authors.

Reference

Schrag A, Hommel ALAJ, Lorenzl S, et al; the CLaSP Consortium. The late stage of Parkinson's —results of a large multinational study on motor and non-motor complications. Parkinsonism Relat Disord. Published online May 21, 2020. doi:10.1016/j.parkreldis.2020.05.016