Prospective longitudinal assessment of hallucinations in Parkinson’s disease

Abstract

Article abstract-Objective: To monitor the evolution of hallucinations over 4 years in a stratified sample of patients with PD. Methods: Using a modified version of the Unified PD Rating Scale (UPDRS) Thought Disorder question, the authors stratified patients into five baseline behavioral groups. They recruited up to 20 patients for each group to participate in sequential interviews (Rush Hallucination Inventory) at baseline and 6, 18, and 48 months. UPDRS motor examinations and Mini Mental State Examinations (MMSE) were obtained at baseline and 48 months. Data were analyzed with Wilcoxon rank sum tests, Mantel-Haenszel tests, and Spearman correlations. To determine features that influenced the new development of hallucinations, a cumulative logit regression model of hallucination severity over time was fit using generalized estimating equations. Results: Based on the design stratification, 60 patients had no hallucinations at baseline (20 with no behavioral problems, 20 with sleep fragmentation, 20 with altered dream phenomena). Twenty-nine patients had hallucinations (20 with retained insight and 9 with loss of insight). At 48 months, the authors could account for all but two subjects (98% retrieval). In 4 years, the presence of hallucinations increased (33% at baseline, 44% at 18 months, and 63% at 48 months, p Ͻ 0.0001). The presence of frequent hallucinations (at least three times weekly) also increased (p ϭ 0.0002). Having hallucinations at baseline or at any given assessment was a strong predictor at all follow-up evaluations of continued hallucinations (p Ͻ 0.0001). Hallucinations were not associated with increased mortality ( 2 ϭ 0.59, df (1), p ϭ 0.47). Among the 60 subjects without hallucinations at baseline, time was the only significant factor influencing the development of hallucination over 48 months. Baseline age, PD duration, sex, medications, and UPDRS or MMSE scores did not influence the incidence of hallucinations. Conclusions: This prospective, longitudinal study documents the persistent and progressive nature of hallucinations in PD patients on chronic dopaminergic therapy. The consistent association of hallucinations with combined levodopa/agonist therapy suggests that these drugs may play a role in the pathophysiology of hallucinations.

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

“…Psychotic symptoms, particularly visual hallucinations and paranoid delusions, occur in up to 40% of patients with Parkinson's disease (PD) who receive dopamine (DA) replacement therapy (Chou et al, 2007;Fenelon et al, 2000;Fernandez et al, 2003: Friedman, 1991, Goetz et al, 2001Weintraub and Stern, 2005;Ravina et al, 2007;Diederich et al, 2009). Psychotic symptoms in PD psychosis (PDP) are a significant cause of distress to patients and their caregivers, and are associated with greater functional impairment, caregiver burden, nursing home placement, and increased mortality (Weintraub and Stern, 2005;Factor et al, 2003).…”

Psychosis in Parkinson’s Disease

“…While there are some data that show persistence of hallucinations in PD patients with drug-induced psychosis after their initial occurrence, there is little direct evidence that confirms the need for lifelong use of antipsychotic agents. 11,12 Moreover, antipsychotic drugs are not completely benign. 49,50 To determine if psychosis-free PD patients could be successfully weaned off their antipsychotic medication, one study prospectively followed PD patients on successful long-term treatment with quetiapine or clozapine as these drugs were withdrawn.…”

“…11 Unfortunately, hallucinations in PD tend to persist and, not uncommonly, may worsen over time. 12 Multiple risk factors for PD-related hallucinations have been identified. Psychotic symptoms usually occur in cases of advanced, chronically treated PD.…”

“…10,15 Chronic exposure to multiple anti-PD medications appears to be a particularly potent risk factor for their occurrence. 16 In Goetz et al's longitudinal assessment of 89 PD patients, 12 low Mini Mental State Examination (MMSE) scores 17 and high Unified Parkinson's Disease Rating Scale (UPDRS) scores were associated with the presence of hallucinations. A cross-sectional study of 172 PD patients found hallucinations to be independently associated with depression, particularly in the young and demented (odds ratios 76.0 and 10.2, respectively) patients.…”

Psychosis in Parkinson’s disease: how should we treat it?

“…In addition, carer burden and mortality are high [7][8][9][10]. There is no consistent relationship with dose, drug type or on-off phenomena [11].…”