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An Alternative Medication for Dementia With Lewy Bodies

Information sourced from NEJM Journal Watch:

An Alternative Medication for Dementia with Lewy Bodies

An antiepileptic drug improves motor symptoms without exacerbating psychiatric symptom

In patients with Parkinson disease (PD) and related disorders such as dementia with Lewy bodies (DLB), psychotic symptoms can develop, especially as a reaction to the dopaminergic medications necessary to improve motor symptoms. Thus, finding alternative medications to treat motor manifestations without producing psychosis is important. This manufacturer-funded, placebo-controlled, randomized, double-blind, phase-2 study explored the efficacy and safety of zonisamide, an FDA-approved anticonvulsant that has been used in Japan adjunctively for PD, in 158 patients diagnosed with probable DLB (mean age, 75; 59% male).

Fluctuating cognition and visual hallucinations were present in 70% of patients. Patients were on levodopa or a decarboxylase inhibitor for more than 12 weeks before a 4-week placebo run-in period; zonisamide was provided at 25 or 50 mg. Discontinuation rates were greater in the 25-mg and 50-mg zonisamide groups (18% and 14%) than in the placebo group (9%), with 137 patients completing treatment.

At 12 weeks, Parkinson-symptom scale ratings improved more with 50-mg zonisamide than with placebo. There was no deterioration in cognition in any group. Adverse effects were more frequent with zonisamide (weight loss, decreased appetite, rash), but the groups did not differ in delusions and visual hallucinations.


It is important that alternative medications for the motor symptoms of DLB not exacerbate the psychiatric symptoms of the illness. Although the mechanism for zonisamide’s effects on parkinsonism is unclear, clinicians might wish also to consider this drug for patients with PD. These options can be discussed with patients and their families, along with the neurologist who may be the primary physician for treating the DLB or PD patient.

Jonathan Silver, MD reviewing Murata M et al. Neurology 2018 Jan 24.


Murata M et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized, double-blind phase 2 study. Neurology 2018 Jan 24; [e-pub].

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