Efficacy of Adjunctive Therapy with Zonisamide Versus Increased Dose of Levodopa for Motor Symptoms in Patients with Dementia with Lewy Bodies: The Randomized, Controlled, Non-Inferiority DUEL Study.

BACKGROUND

In patients with dementia with Lewy bodies (DLB), it is unknown whether adjunct zonisamide is as effective and safe as increasing levodopa dose when levodopa has inadequate efficacy on parkinsonism.

OBJECTIVE

To compare adjunct zonisamide 25 mg/day versus an increased levodopa dose (increased by 100 mg/day) in patients with DLB treated with levodopa ≤300 mg/day for parkinsonism.

METHODS

The DUEL study was a multicenter, randomized, controlled, open-label, parallel-group, interventional, non-inferiority trial. During the observation period, levodopa was administered at ≤300 mg/day for 4 weeks. Subsequently, patients were randomized to receive adjunct zonisamide 25 mg/day or levodopa increased by 100 mg/day.

RESULTS

Respective adjusted mean changes in MDS-UPDRS Part III total score at 16 and 24 weeks (primary endpoint) were -6.3 and -4.4 in the zonisamide add-on and -0.8 and 2.0 in the levodopa increase groups. The adjusted mean difference at 24 weeks was -6.4 (95% confidence interval [CI] -13.5, 0.7); the upper limit of the 95% CI (0.7) was lower than the non-inferiority margin (3.0). No significant between-group differences were observed in total scores of the MDS-UPDRS Part II, Eating Questionnaire, EuroQol-5 dimension-5 level, Zarit Caregiver Burden Interview, or other secondary endpoints. No notable between-group differences were observed in adverse event incidences.

CONCLUSION

Adjunct zonisamide 25 mg/day may yield moderate improvement in motor symptoms in patients with DLB when the levodopa effect is insufficient, but it could not be verified that the zonisamide 25 mg/day was as effective as levodopa 100 mg/day because levodopa showed no sufficient efficacy as assumed.