Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study.

Area of Science:

• Neurology
• Pharmacology
• Geriatrics

Background:

• Dementia with Lewy bodies (DLB) is characterized by cognitive decline, parkinsonism, and psychiatric symptoms.
• Levodopa is a primary treatment for parkinsonism in DLB, but its efficacy can be limited.
• Adjunctive therapies are sought to improve motor symptoms without exacerbating cognitive or behavioral issues.

Purpose of the Study:

• To evaluate the efficacy and safety of zonisamide as an add-on therapy to levodopa for parkinsonism in DLB patients.
• To assess the impact of zonisamide on cognitive function, behavioral and psychological symptoms of dementia (BPSD), and caregiver burden.

Main Methods:

• A phase 2, randomized, double-blind, placebo-controlled trial.
• 158 outpatients with probable DLB were randomized to receive placebo or zonisamide (25 or 50 mg daily) for 12 weeks, alongside their existing levodopa therapy.
• Primary endpoint: change in Unified Parkinson's Disease Rating Scale (UPDRS) part 3 score at 12 weeks. Secondary endpoints included cognitive function, BPSD, and safety.

Main Results:

• Zonisamide 50 mg significantly improved UPDRS part 3 scores compared to placebo (p=0.003).
• No worsening of cognitive function, BPSD, or caregiver burden was observed with zonisamide.
• Higher incidence of overall adverse events in the 50 mg zonisamide group (65.3%) versus placebo (50.0%), with similar rates of serious adverse events.

Conclusions:

• Adjunctive zonisamide to levodopa therapy is effective in improving parkinsonism in DLB patients.
• Zonisamide is well-tolerated and does not worsen cognitive or psychiatric symptoms in this population.
• Class I evidence supports the use of zonisamide for parkinsonism in DLB.