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Treatment in Psychiatry   |    
Behavioral and Psychiatric Symptoms in Prion Disease
Andrew Thompson, B.Sc., M.R.C.P.; Angus MacKay, Ph.D., F.R.C.Psych.; Peter Rudge, F.R.C.P.; Ana Lukic, B.Sc., M.R.C.P.; Marie-Claire Porter, B.Sc., M.R.C.P.; Jessica Lowe, B.Sc.; John Collinge, F.R.C.P., F.R.S.; Simon Mead, Ph.D., F.R.C.P.
Am J Psychiatry 2014;171:265-274. doi:10.1176/appi.ajp.2013.12111460
View Author and Article Information

Prof. Collinge is a director and shareholder of D-Gen Limited, an academic spinout company working in the field of prion disease diagnosis, decontamination, and therapeutics. The other authors report no financial relationships with commercial interests.

Supported by the MRC and the Department of Health (England). This research was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centre's funding scheme. The MRC and the Department of Health funded the PRION-1 trial (G0400713).

From the National Health Service (NHS) National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London; the NHS Highland Mental Health Services, Argyll and Bute Hospital, Blarbuie Road, Lochgilphead, Scotland; and the Medical Research Council (MRC) Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London.

Address correspondence to Dr. Mead (s.mead@prion.ucl.ac.uk).

Copyright © 2014 by the American Psychiatric Association

Received November 23, 2012; Revised May 19, 2013; Accepted May 28, 2013.

Abstract

The prion diseases are rare neurodegenerative conditions that cause complex and highly variable neuropsychiatric syndromes, often with remarkably rapid progression. Prominent behavioral and psychiatric symptoms have been recognized since these diseases were first described. While research on such symptoms in common dementias has led to major changes in the way these symptoms are managed, evidence to guide the care of patients with prion disease is scarce. The authors review the published research and draw on more than 10 years’ experience at the U.K. National Prion Clinic, including two large prospective clinical research studies in which more than 300 patients with prion disease have been followed up from diagnosis to death, with detailed observational data gathered on symptomatology and symptomatic treatments. The authors group behavioral and psychiatric symptoms into psychotic features, agitated features, and mood disorder and describe their natural history, showing that they spontaneously improve or resolve in many patients and are short-lived in many others because of rapid progression of global neurological disability. Diagnostic category, disease severity, age, gender, and genetic variation are or may be predictive factors. The authors review the observational data on pharmacological treatment of these symptoms in the U.K. clinical studies and make cautious recommendations for clinical practice. While nonpharmacological measures should be the first-line interventions for these symptoms, the authors conclude that there is a role for judicious use of pharmacological agents in some patients: antipsychotics for severe psychosis or agitation; benzodiazepines, particularly in the late stages of disease; and antidepressants for mood disorder.

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FIGURE 1. Natural History of Hallucinations and Depressive Symptoms in Prion Diseasea

a The panels on the left present the prevalence of hallucinations and depressive symptoms (at all assessments), grouped by stage of disease progression; the panels on the right summarize severity ratings of hallucinations and depressive symptoms at the assessment following one in which these symptoms were rated “often” or “always.” Disease progression was assessed by score on the Medical Research Council Prion Disease Rating Scale (MRC-PDRS), on which 0=maximal impairment, akinetic and mute, and 20=no functional impairment.

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TABLE 1.Summary of Patient Diagnoses in the PRION-1 and National Prion Monitoring Cohort Studies
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a CJD=Creutzfeldt-Jakob disease; OPRI=octapeptide repeat insertion.

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TABLE 2.Prevalence of Behavioral and Psychiatric Symptoms (BPS) in All Symptomatic Patients and in Individual Prion Disease Types, at Illness Onset and at Any Stage of Disease, in the PRION-1 and National Prion Monitoring Cohort Studiesa
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a sCJD=sporadic Creutzfeldt-Jakob disease; vCJD=variant Creutzfeldt-Jakob disease; iCJD=iatrogenic Creutzfeldt-Jakob disease; IPD=inherited prion diseases; OPRI=octapeptide repeat insertion.

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TABLE 3.Drug Treatment of Behavioral and Psychiatric Symptoms in the PRION-1 and National Prion Monitoring Cohort Studiesa
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a Observational data for all drug classes prescribed five or more times for each symptom group. Some patients received more than one agent (most commonly an antipsychotic and a benzodiazepine), but in most cases the two agents were not started simultaneously. As far as possible, the relative clinical benefit and adverse effects of each were determined from careful review of the clinical notes. If this was not clear, the benefit or adverse effect was attributed to both.

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b Number of prescriptions studied.

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c Midazolam (N=16), diazepam (N=12), lorazepam (N=7), clonazepam (N=4).

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d Quetiapine (N=11), haloperidol (N=6), risperidone (N=4), olanzapine (N=2).

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e Amitriptyline (N=2), mirtazapine (N=2), fluoxetine (N=1), sertraline (N=1).

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f Lorazepam (N=12), diazepam (N=6), midazolam (N=6), clonazepam (N=4), temazepam (N=3), alprazolam (N=1).

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g Quetiapine (N=14), olanzapine (N=8), risperidone (N=6), haloperidol (N=2), levomepromazine (N=1).

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h Donepezil (N=4), rivastigmine (N=1).

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i Citalopram (N=21), fluoxetine (N=7), mirtazapine (N=6), sertraline (N=3), amitriptyline (N=2), escitalopram (N=2), clomipramine (N=1), paroxetine (N=1), trazodone (N=1), venlafaxine (N=1).

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