User login
Zonisamide may improve parkinsonism in patients with dementia with Lewy bodies (DLB) without worsening cognitive function or psychiatric symptoms, according to a study published in the February 20 issue of Neurology.
“This study provides Class I evidence that zonisamide (adjunctive to levodopa) improves parkinsonism and is well tolerated in patients with DLB,” said Miho Murata, MD, PhD, of the National Center of Neurology and Psychiatry in Tokyo, and colleagues. “We found that the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 total score at week 12 was significantly improved in the zonisamide 50 mg/day group, compared with the placebo group.”
Four placebo-controlled, randomized trials have found that zonisamide—a drug used to treat seizures—improves motor symptoms in Parkinson’s disease with a low incidence of motor complications such as dyskinesia or psychiatric symptoms such as hallucinations. In another study that included three patients with DLB, zonisamide was associated with improved parkinsonism and reduced caregiver burden without worsening cognition or behavioral or psychological symptoms.
A Phase II, Placebo-Controlled, Double-Blind Study
Based on results from these studies, Dr. Murata and colleagues conducted a phase II, placebo-controlled, randomized double-blind study to examine the efficacy and safety of zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with DLB.
Eligible participants were between ages 20 and 84 and had a UPDRS part 3 score of 10 or greater. The investigators excluded patients with Parkinson’s disease with dementia (ie, well-established Parkinson’s disease followed by onset of dementia), those who did not respond to levodopa therapy, and patients with epilepsy.
The primary end point was change from baseline in UPDRS part 3 score at week 12. Secondary end points included changes from baseline in total UPDRS score, each UPDRS part, and each UPDRS item at each evaluation.
The study included a four-week run-in period and a 12-week treatment period. During the run-in period, patients received placebo tablets once daily under single-blind conditions to eliminate any confounding effects of other antiparkinson drugs.
Participants were randomized 1:1:1 to placebo, zonisamide (25 mg), or zonisamide (50 mg) daily. Patients visited study sites every four weeks for five visits. Dosage and administration of antidementia drugs were unchanged from 12 weeks before the run-in period throughout the treatment period. Dosage and administration of levodopa/decarboxylase inhibitor therapy and other antiparkinson, antihypertensive, CNS, cardiovascular, or gastrointestinal drugs or herbal medicine were unchanged from two weeks before the run-in period throughout the treatment period.
Zonisamide Did Not Worsen Cognitive Function or Behavior
In all, 158 patients were randomized to receive zonisamide or placebo, and 137 patients completed treatment. Zonisamide (50 mg) was associated with significantly greater improvement in UPDRS part 3 scores at week 12, compared with placebo (between group difference, –4.1). In addition, zonisamide did not worsen cognitive function, behavior or psychological symptoms of dementia, or caregiver burden.
The incidence of adverse events was higher in the zonisamide (50 mg) group than in the zonisamide (25 mg) group and placebo group (65.3%, 43.1%, and 50.0%, respectively). The incidences of common drug-related adverse events (eg, decreased weight, decreased appetite, and rash) were higher among patients who received zonisamide, compared with patients who received placebo. The rates of serious adverse events were similar between the groups.
“There is an urgent need for new treatments for DLB,” said Linda A. Hershey, MD, PhD, Professor of Neurology at the University of Oklahoma Health Sciences Center in Oklahoma City, who wrote an accompanying editorial. “The successful execution of this trial is a major accomplishment, which provides evidence that future trials are warranted.”
—Erica Tricarico
Suggested Reading
Hershey LA, Irwin DJ. Zonisamide for DLB parkinsonism: An old drug used in a new context. Neurology. 2018;90(8):349-350.
Murata M, Odawara T, Hasegawa K, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study. Neurology. 2018;90(8):e664-e672.
Zonisamide may improve parkinsonism in patients with dementia with Lewy bodies (DLB) without worsening cognitive function or psychiatric symptoms, according to a study published in the February 20 issue of Neurology.
“This study provides Class I evidence that zonisamide (adjunctive to levodopa) improves parkinsonism and is well tolerated in patients with DLB,” said Miho Murata, MD, PhD, of the National Center of Neurology and Psychiatry in Tokyo, and colleagues. “We found that the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 total score at week 12 was significantly improved in the zonisamide 50 mg/day group, compared with the placebo group.”
Four placebo-controlled, randomized trials have found that zonisamide—a drug used to treat seizures—improves motor symptoms in Parkinson’s disease with a low incidence of motor complications such as dyskinesia or psychiatric symptoms such as hallucinations. In another study that included three patients with DLB, zonisamide was associated with improved parkinsonism and reduced caregiver burden without worsening cognition or behavioral or psychological symptoms.
A Phase II, Placebo-Controlled, Double-Blind Study
Based on results from these studies, Dr. Murata and colleagues conducted a phase II, placebo-controlled, randomized double-blind study to examine the efficacy and safety of zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with DLB.
Eligible participants were between ages 20 and 84 and had a UPDRS part 3 score of 10 or greater. The investigators excluded patients with Parkinson’s disease with dementia (ie, well-established Parkinson’s disease followed by onset of dementia), those who did not respond to levodopa therapy, and patients with epilepsy.
The primary end point was change from baseline in UPDRS part 3 score at week 12. Secondary end points included changes from baseline in total UPDRS score, each UPDRS part, and each UPDRS item at each evaluation.
The study included a four-week run-in period and a 12-week treatment period. During the run-in period, patients received placebo tablets once daily under single-blind conditions to eliminate any confounding effects of other antiparkinson drugs.
Participants were randomized 1:1:1 to placebo, zonisamide (25 mg), or zonisamide (50 mg) daily. Patients visited study sites every four weeks for five visits. Dosage and administration of antidementia drugs were unchanged from 12 weeks before the run-in period throughout the treatment period. Dosage and administration of levodopa/decarboxylase inhibitor therapy and other antiparkinson, antihypertensive, CNS, cardiovascular, or gastrointestinal drugs or herbal medicine were unchanged from two weeks before the run-in period throughout the treatment period.
Zonisamide Did Not Worsen Cognitive Function or Behavior
In all, 158 patients were randomized to receive zonisamide or placebo, and 137 patients completed treatment. Zonisamide (50 mg) was associated with significantly greater improvement in UPDRS part 3 scores at week 12, compared with placebo (between group difference, –4.1). In addition, zonisamide did not worsen cognitive function, behavior or psychological symptoms of dementia, or caregiver burden.
The incidence of adverse events was higher in the zonisamide (50 mg) group than in the zonisamide (25 mg) group and placebo group (65.3%, 43.1%, and 50.0%, respectively). The incidences of common drug-related adverse events (eg, decreased weight, decreased appetite, and rash) were higher among patients who received zonisamide, compared with patients who received placebo. The rates of serious adverse events were similar between the groups.
“There is an urgent need for new treatments for DLB,” said Linda A. Hershey, MD, PhD, Professor of Neurology at the University of Oklahoma Health Sciences Center in Oklahoma City, who wrote an accompanying editorial. “The successful execution of this trial is a major accomplishment, which provides evidence that future trials are warranted.”
—Erica Tricarico
Suggested Reading
Hershey LA, Irwin DJ. Zonisamide for DLB parkinsonism: An old drug used in a new context. Neurology. 2018;90(8):349-350.
Murata M, Odawara T, Hasegawa K, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study. Neurology. 2018;90(8):e664-e672.
Zonisamide may improve parkinsonism in patients with dementia with Lewy bodies (DLB) without worsening cognitive function or psychiatric symptoms, according to a study published in the February 20 issue of Neurology.
“This study provides Class I evidence that zonisamide (adjunctive to levodopa) improves parkinsonism and is well tolerated in patients with DLB,” said Miho Murata, MD, PhD, of the National Center of Neurology and Psychiatry in Tokyo, and colleagues. “We found that the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 total score at week 12 was significantly improved in the zonisamide 50 mg/day group, compared with the placebo group.”
Four placebo-controlled, randomized trials have found that zonisamide—a drug used to treat seizures—improves motor symptoms in Parkinson’s disease with a low incidence of motor complications such as dyskinesia or psychiatric symptoms such as hallucinations. In another study that included three patients with DLB, zonisamide was associated with improved parkinsonism and reduced caregiver burden without worsening cognition or behavioral or psychological symptoms.
A Phase II, Placebo-Controlled, Double-Blind Study
Based on results from these studies, Dr. Murata and colleagues conducted a phase II, placebo-controlled, randomized double-blind study to examine the efficacy and safety of zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with DLB.
Eligible participants were between ages 20 and 84 and had a UPDRS part 3 score of 10 or greater. The investigators excluded patients with Parkinson’s disease with dementia (ie, well-established Parkinson’s disease followed by onset of dementia), those who did not respond to levodopa therapy, and patients with epilepsy.
The primary end point was change from baseline in UPDRS part 3 score at week 12. Secondary end points included changes from baseline in total UPDRS score, each UPDRS part, and each UPDRS item at each evaluation.
The study included a four-week run-in period and a 12-week treatment period. During the run-in period, patients received placebo tablets once daily under single-blind conditions to eliminate any confounding effects of other antiparkinson drugs.
Participants were randomized 1:1:1 to placebo, zonisamide (25 mg), or zonisamide (50 mg) daily. Patients visited study sites every four weeks for five visits. Dosage and administration of antidementia drugs were unchanged from 12 weeks before the run-in period throughout the treatment period. Dosage and administration of levodopa/decarboxylase inhibitor therapy and other antiparkinson, antihypertensive, CNS, cardiovascular, or gastrointestinal drugs or herbal medicine were unchanged from two weeks before the run-in period throughout the treatment period.
Zonisamide Did Not Worsen Cognitive Function or Behavior
In all, 158 patients were randomized to receive zonisamide or placebo, and 137 patients completed treatment. Zonisamide (50 mg) was associated with significantly greater improvement in UPDRS part 3 scores at week 12, compared with placebo (between group difference, –4.1). In addition, zonisamide did not worsen cognitive function, behavior or psychological symptoms of dementia, or caregiver burden.
The incidence of adverse events was higher in the zonisamide (50 mg) group than in the zonisamide (25 mg) group and placebo group (65.3%, 43.1%, and 50.0%, respectively). The incidences of common drug-related adverse events (eg, decreased weight, decreased appetite, and rash) were higher among patients who received zonisamide, compared with patients who received placebo. The rates of serious adverse events were similar between the groups.
“There is an urgent need for new treatments for DLB,” said Linda A. Hershey, MD, PhD, Professor of Neurology at the University of Oklahoma Health Sciences Center in Oklahoma City, who wrote an accompanying editorial. “The successful execution of this trial is a major accomplishment, which provides evidence that future trials are warranted.”
—Erica Tricarico
Suggested Reading
Hershey LA, Irwin DJ. Zonisamide for DLB parkinsonism: An old drug used in a new context. Neurology. 2018;90(8):349-350.
Murata M, Odawara T, Hasegawa K, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study. Neurology. 2018;90(8):e664-e672.