Review
Parkinson’s disease psychosis 2010: A review article

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Abstract

Psychotic symptoms are common in Parkinson’s disease (PD), generally associated with the medications used to treat the motor symptoms. On rare occasion they occur in patients not taking medication for PD. Psychotic symptoms are usually hallucinations, typically visual, less commonly auditory, and rarely in other domains. Hallucinations are generally stereotyped and without emotional content. Initially patients usually have insight so that the hallucinations are benign in terms of their immediate impact but have poor prognostic implications, with increased risk of dementia, worsened psychotic symptoms and mortality. Delusions occur in about 5–10% of drug treated patients and are considerably more disruptive, being paranoid in nature, often of spousal infidelity or abandonment by family. Treatment of Parkinson’s disease psychosis (PDP) focuses on reducing the psychiatric symptom load while balancing the competing problem of mobility. Contributors to the psychotic symptoms should be searched for, such as systemic illness and other psycho-active medications. If none are identified or can be eliminated then the PD medications should be reduced to the lowest levels that allow tolerable motor function. Once this level has been reached there are two schools of thought on treatment, using either acetylcholinesterase inhibitors or atypical anti-psychotics. Only clozapine has level I evidence to support its use. Quetiapine is the only other anti-psychotic free of motor side effects, but it has failed double blind placebo controlled trials to demonstrate efficacy.

Section snippets

Psychosis and psychotic symptoms

The term “psychosis” has been replaced in recent years by the term “psychotic syndrome,” in which patients show signs of specific psychotic symptoms [1]. The older definition used “loss of reality testing” as the primary determinant. In the case of people with Parkinson’s disease (PD) the predominant symptoms are hallucinations and delusions [2], [3], [4], [5], [6]. Hallucinations are sensory phenomena that are not induced by physical stimuli. These occur in each sensory modality: visual,

Conclusion

Psychotic symptoms are common in PD, and although they may appear in the absence of medication [13], [15] primarily develop in patients who take medications to improve mobility, at least in the financially developed world. The psychotic symptoms are predominantly hallucinations, with visual being the most common, followed by auditory, and are quite stereotypic and fixed for each individual. Delusions are the next most common symptom, and these too are stereotypic, being mostly paranoid, in

Conflict of interest

Conflicts of interest last 12 months: Teva, Acadia Pharmaceuticals, EMD Serono, Glaxo Smith Kline, Ingelheim-Boehringer, Cephalon, NIH, MJ Fox Foundation.

Conflicts of interest in last 10 years include manufacturers of each atypical anti-psychotic drug as a consultant: Astra Zeneca, Novartis, Bristol Myers Squibb, Eli Lilly, Pfizer, Ovation.

References (106)

  • A. Breier et al.

    Olanzapine in the treatment of dopamimetic-induced psychosis in patient with Parkinson’s disease

    Biol Psychol

    (2002)
  • J. Schindehutte et al.

    Treatment of drug-induced psychosis in Parkinson’s disease with ziprasidone can induce severe dose-dependent off-periods and pathological laughing

    Clin Neurol Neurosurg

    (2007)
  • J. Zoldan et al.

    Ondansetron for hallucinosis in advanced Parkinson’s disease

    Lancet

    (1993)
  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders

    (2000)
  • S. Papapetropoulos et al.

    Psychotic symptom in Parkinson’s disease. From description to etiology

    J Neurol

    (2005)
  • G. Fenelon et al.

    Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors

    Brain

    (2000)
  • K.L. Chou et al.

    Drug-induced psychosis in Parkinson disease: phenomenology and correlations among psychosis rating instruments

    Clin Neuropharmacol

    (2005)
  • C.G. Goetz

    Hallucinations Parkinson’s disease clinical syndrome

    Adv Neurol

    (1999)
  • C.G. Goetz et al.

    Pharmacology of hallucinations induced by long-term therapy

    Am J Psychiatry

    (1982)
  • B. Ravina et al.

    Diagnostic criteria for psychosis in Parkinson’s disease: report of an NIND, NIMH work group

    Mov Disord

    (2007)
  • J.H. Friedman

    The management of the levodopa psychoses

    Clin Neuropharmacol

    (1991)
  • B. Sadock et al.
  • C.G. Goetz et al.

    Hallucinations and sleep disorders in Parkinson’s disease: six-year prospective longitudinal study

    Neurol

    (2005)
  • G. Fenelon et al.

    Hallucinations in Parkinson’s disease in the pre-levodopa era

    Neurology

    (2006)
  • I.G. McKeith et al.

    Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium

    Neurology

    (2005)
  • Parant [cited in...
  • N.J. Diederich et al.

    Hallucinations in Parkinson disease

    Nat Rev Neurol

    (2009)
  • H. Mjones

    Paralysis agitans. A clinical and genetic study

    (1949)
  • A.J. Harding et al.

    Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe

    Brain

    (2002)
  • D. Aarsland et al.

    A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson’s disease with and without dementia

    Int J Geriatr Psychiatry

    (2001)
  • M. Kitayama et al.

    Clinical evaluation of Parkinson’s disease dementia: association with ageing and visual hallucinations

    Acta Neurol Scand

    (2007)
  • I. Arnulf et al.

    Hallucination, REM sleep, and Parkinson’s disease: a medical hypothesis

    Neurology

    (2000)
  • A. Kurita et al.

    Visual hallucinations and altered visual information processing in Parkinson disease and dementia with Lewy bodies

    Mov Disord

    (2010)
  • N. Ibarretxe-Bilbao et al.

    Differential progression of brain atrophy in Parkinson disease with and without visual hallucinations

    J Neuorol Neurosurg Psychiatr

    (2009)
  • A.M. Meppelink et al.

    Impaired visual processing preceding image recognition in Parkinson’s disease patient with visual hallucinations

    Brain

    (2009)
  • S. Holroyd et al.

    Prospective study of hallucinations and delusions in Parkinson’s disease

    J Neurol Neurosurg Psychiatr

    (2001)
  • H.H. Fernandez et al.

    Scales to assess psychosis in Parkinson’s disease

    Mov Disord

    (2008)
  • C.G. Goetz et al.

    Hallucinations and sleep disorders in Parkinson’s disease: six-year prospective longitudinal study

    Neurology

    (2005)
  • C.G. Goetz et al.

    The malignant course of “benign hallucinations” in Parkinson’s disease

    Arch Neurol

    (2006)
  • C.G. Goetz et al.

    Risk factors for nursing home placement in advanced Parkinson’s disease

    Neurology

    (1993)
  • C.G. Goetz et al.

    Mortality and hallucinations in nursing home patients with advanced Parkinson’s dissase

    Neurology

    (1995)
  • Parkinson Study Group

    Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease

    N Engl J Med

    (1999)
  • S.A. Factor et al.

    Clozapine: a 2-year open trial in Parkinson’s disease patients with psychosis

    Neurology

    (1994)
  • J.H. Friedman

    ‘Drug Holiday’ in the treatment of Parkinson’s disease: a brief review

    Arch Intern Med

    (1985)
  • C. Moskowitz et al.

    Levodopa-induced psychosis: a kindling phenomenon

    Am J Psychiatry

    (1978)
  • E. Scholz et al.

    Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine

    Eur Arch Psychiatry Neurol Sci

    (1985)
  • J.H. Friedman et al.

    Idiopathic Parkinson disease in a chronic schizophrenic patient: long term treatment with clozapine and l-Dopa

    Clin Neuropharmacol

    (1987)
  • J.H. Friedman et al.

    Autopsy follow up of a patient with schizophrenia and presumed idiopathic Parkinson disease

    Clin Neuropharmacol

    (2001)
  • J. Crilly

    History of clozapine and its emergence in the US market: review and analysis

    Hist Psychiatry

    (2007)
  • J.M. Miyasaki et al.

    Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology

    Neurology

    (2006)
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    The review of this paper was entirely handled by the Co-Editor-in-Chief, Zbigniew Wszolek.

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