Rivastigmine for minor visual hallucinations in Parkinson's disease:A randomized controlled trial with 24 months follow-up

Background Visual hallucinations are common in patients with Parkinson's disease and represent probably the major independent predictor for cognitive deterioration and nursing home placement. Objective To investigate if treatment of minor visual hallucinations in Parkinson's disease with rivastigmine delays the progression to psychosis. Methods A multicenter, randomized, double-blind, placebo-controlled trial was conducted which aimed to recruit 168 patients with Parkinson's disease reporting minor visual hallucinations 4 weeks before it. Important exclusion criteria were Parkinson's disease dementia, current delirium, and treatment with antipsychotics or drugs that have significant anti-cholinergic side effects. Subjects were randomized to rivastigmine capsules, 3-6 mg twice a day, or placebo for 24 months. The primary outcome was the time to Parkinson's disease psychosis, which was defined as the need to start with antipsychotics. Results The trial was stopped prematurely because of slow recruitment. Ninety-one patients were randomized: 46 patients were assigned to rivastigmine and 45 patients to placebo. No effect of rivastigmine could be demonstrated on the transition time to psychosis or dementia during the 24-month follow-up period. After 6 months of study treatment, cognition, mood, motor performance, and non-motor performance did not differ significantly between the rivastigmine-group and the placebo-group. Conclusions Because the study was terminated early, it was insufficiently powered to properly evaluate the primary outcome. The limited data of the study favor a wait and see approach instead of early treatment with rivastigmine in PD patients with minor VH.