Quetiapine and Clozapine in Parkinsonian Patients With Dopaminergic Psychosis

Morgante, Francesca; Epifanio, Antonio; Spina, Edoardo; Zappia, Mario; Rosa, A. E. Di; Marconi, Roberto; Basile, Giorgio; Raimondo, Giorgio Di; Spina, Paolo; Quattrone, Aldo

doi:10.1097/01.wnf.0000136891.17006.ec

Cited by 200 publications

(127 citation statements)

References 26 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Meltzer

Mills

Revell

et al. 2009

Neuropsychopharmacol

269

173

View full text Add to dashboard Cite

Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD). Clozapine and quetiapine, two atypical antipsychotic drugs, at doses markedly lower than those effective in schizophrenia, which, nevertheless, still cause sedation, hypotension, and other side effects, are widely used to treat psychotic symptoms in patients with PD psychosis (PDP), although quetiapine has never been shown to be effective in a placebo-controlled study. The demonstrated efficacy of clozapine in PDP has been attributed to serotonin (5-HT 2A ) receptor blockade. We postulated that pimavanserin (ACP-103), a highly selective 5-HT 2A inverse agonist, would attenuate psychosis in patients with PDP, but avoid motoric worsening and non-motoric side effects. In this double-blind, randomized multicenter 28-day study, the tolerability and efficacy of pimavanserin was compared with placebo in 60 patients with L-DOPA or dopamine (DA) agonist-induced PDP. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. Antipsychotic efficacy was evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS) and a UPDRS Part I psychosisrelevant item. Pimavanserin did not differentiate from placebo with regard to motor impairment, sedation, hypotension, or other side effects. The principal measures of efficacy of antipsychotic response to pimavanserin, the SAPS total domain score, only showed a trend. However, the pimavanserin-treated patients showed significantly greater improvement in some but not all measures of psychosis, including SAPS global measures of hallucinations and delusions, persecutory delusions, and the UPDRS measure of delusions and hallucinations. Pimavanserin showed significantly greater improvement in psychosis in patients with PDP at a dose which did not impair motor function, or cause sedation or hypotension Thus, pimavanserin may represent a novel treatment for PDP. Furthermore, these results support the hypothesis that attenuation of psychosis secondary to DA receptor stimulation in PDP may be achieved through selective 5-HT 2A receptor antagonism.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Meltzer

Mills

Revell

et al. 2009

Neuropsychopharmacol

269

173

View full text Add to dashboard Cite

show abstract

“…Open label trials, published after the double blind trials began reported results similar to the double blind, controlled trials [78]Results for risperidone [79][80][81][82], ziprasidone [83,84] and aripiprazole [85][86][87] have all been open label and conflicting in their outcomes, with some demonstrating worsened parkinsonism [81,83,88,89] and others reporting good tolerance [79,80,[90][91][92], without worsening of motor function. Some reports have found "non-inferiority" of drugs compared to clozapine [93][94][95]. The drugs have generally been reported helpful for the psychosis, although not uniformly.…”

Section: Managementmentioning

confidence: 99%

“…In addition, risperidone, olanzapine, ziprasidone and aripiprazole have frequently been associated with dose-dependent neuroleptic induced parkinsonism in otherwise normal psychotic patients (personal observation). 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.…”

Section: Managementmentioning

confidence: 99%

Parkinson Disease Psychosis: Update

Friedman

2013

Behavioural Neurology

View full text Add to dashboard Cite

Abstract. Psychotic symptoms are common in drug treated patients with Parkinson's disease (PD). Visual hallucinations occur in about 30% and delusions, typically paranoid in nature, occur in about 5%. These problems, particularly the delusions, cause great distress for patient and caregivers, and are among the most important precipitants for nursing home placement. Psychotic symptoms carry a poor prognosis. They often herald dementia, and are associated with increased mortality. These symptoms often abate with medication reductions, but this may not be tolerated due to worsened motor function. Only clozapine has level A evidence to support its use in PD patients with psychosis (PDP), whether demented or not. While quetiapine has been recommended by the American Academy of Neurology for "consideration," double blind placebo controlled trials have demonstrated safety but not efficacy. Other antipsychotic drugs have been reported to worsen motor function and data on the effectiveness of cholinesterase inhibitors is limited. PDP remains a serious problem with limited treatment options.

show abstract

“…Two clinical trials 46 ,47 were head-to· head comparisons of clozapine and quetiapine (Table V) Morgante et al 46 reported on a randomized, open-label, rater-blinded, comparison trial of quetiapine and dozapine, using the BPRS and CGI as the primary outcome measures; 45 patients were induded in this study, 40 of whom completed the study (completion rate, 88.9%). Three ( 13.0%) of2 3 patients in the dozapine group and 1 (4.5%) of22 patients in the quetiapine group did not complete the study.…”

Section: Comparison Studiesmentioning

confidence: 99%

Management of hallucinations and psychosis in Parkinson's disease

Eng

Welty

2010

The American Journal of Geriatric Pharmacotherapy

View full text Add to dashboard Cite

Abstract:BACKGROUND: Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published. OBJECTIVE: The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD. METHODS: A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. RESULTS: Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years. CONCLUSIONS: Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts. Eng, Marty L. and Welty, Timothy E. (1999) Management of Hallucinations and Psychosis in Parkinson's Disease. Am J Geriat Pharm. 8(4), 316-330. PMID: 20869621. Publisher's official version:

show abstract

Quetiapine and Clozapine in Parkinsonian Patients With Dopaminergic Psychosis

Abstract: Quetiapine and clozapine appear equally efficacious for treatment of dopaminergic psychosis in patients with PD.

Cited by 200 publications

References 26 publications

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

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

Parkinson Disease Psychosis: Update

Management of hallucinations and psychosis in Parkinson's disease

Contact Info

Product

Resources

About