Double‐blind, placebo‐controlled, unforced titration parallel trial of quetiapine for dopaminergic‐induced hallucinations in Parkinson's disease

Abstract

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.

Pimavanserin, a Serotonin2A Receptor Inverse Agonist, for the Treatment of Parkinson's Disease Psychosis

“…Quetiapine, another atypical antipsychotic drug, has been reported in a number of open-label studies to reduce psychosis in PD without worsening motor symptoms, but sedative and hypotensive effects also limit its tolerability (Fernandez et al, 1999Reddy et al, 2002;Mancini et al, 2004;Morgante et al, 2004;Merims et al, 2006). Furthermore, in three placebo-controlled, double-blind, randomized trials, quetiapine failed to show superiority to placebo on measures of psychosis in PDP (Ondo et al, 2005;Rabey et al, 2006;Shotbolt et al, 2009). Nevertheless, it remains widely used as the initial drug treatment for PDP, at doses from 25 to 300 mg/day, and is the drug of choice for PDP according to the American Academy of Neurology Practice Parameters Task Force on the treatment of PD (Miyasaki et al, 2006); clozapine is recommended only after quetiapine fails to manage psychotic symptoms (Chou et al, 2007;Reddy et al, 2002;Mancini et al, 2004).…”

Parkinson’s Disease Psychosis – Patterns of Care and Treatment in the EU-5 from Neurologists’ Perspective

“…12,13 Quetiapine is not licensed for the treatment of PDP despite being listed as a therapeutic option in guidelines. [5][6][7][8]14 However, data from double-blind, randomized controlled trials evaluating quetiapine in patients with PDP have been mixed, 13 with four studies reporting no significant improvement in symptoms of psychosis over placebo, [15][16][17][18] and one study reporting a significant decrease in hallucinations. 19 A new atypical antipsychotic, pimavanserin, received regulatory approval in the US in April 2016 for the treatment of hallucinations and delusions associated with PDP.…”

Parkinson Disease Psychosis: Update

“…Open label studies showed quetiapine to be well tolerated and an effective antipsychotic for PDP [96][97][98] and in comparison trial [95] to be non-inferior to clozapine. Unfortunately, three double blind controlled trials did not find efficacy [99][100][101], although all confirmed that the drug was free of motor worsening. One small DBPCT study [102] did find efficacy and tolerance but the numbers are too small to be persuasive.…”