Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review)

Objective: To make evidence-based treatment recommendations for patients with Parkinson disease (PD) with dementia, depression, and psychosis based on these questions: 1) What tools are effective to screen for depression, psychosis, and dementia in PD? 2) What are effective treatments for depression and psychosis in PD? 3) What are effective treatments for PD dementia or dementia with Lewy bodies (DLB)? Methods: A nine-member multispecialty committee evaluated available evidence from a structured literature review using MEDLINE, and the Cochrane Database of Health and Psychosocial Instruments from 1966 to 2004. Additional articles were identified by panel members. Results: The Beck Depression Inventory-I, Hamilton Depression Rating Scale, and Montgomery Asberg Depression Rating Scale should be considered to screen for depression in PD (Level B). The Mini-Mental State Examination and the Cambridge Cognitive Examination should be considered to screen for dementia in PD (Level B). Amitriptyline may be considered to treat depression in PD without dementia (Level C). For psychosis in PD, clozapine should be considered (Level B), quetiapine may be considered (Level C), but olanzapine should not be considered (Level B). Donepezil or rivastigmine should be considered for dementia in PD (Level B) and rivastigmine should be considered for DLB (Level B). Conclusions: Screening tools are available for depression and dementia in patients with PD, but more specific validated tools are needed. There are no widely used, validated tools for psychosis screening in Parkinson disease (PD). Clozapine successfully treats psychosis in PD. Cholinesterase inhibitors are effective treatments for dementia in PD, but improvement is modest and motor side effects may occur. NEUROLOGY 2006;66:996–1002 Statement of purpose. The Quality Standards Subcommittee (QSS) develops scientifically sound, clinically relevant practice parameters to guide the practice of neurology. This article discusses treatments for the management of patients with depression, psychosis, and dementia in Parkinson disease (PD). These recommendations address the needs of neurologists and other clinicians caring for people with PD, patients and caregivers, research funding agencies, and researchers in movement disorders. Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 11 issue to find the title link for this article. Editorial, see page 966 See also pages 968, 976, and 983 This article was previously published in electronic format as an Expedited E-Pub at www.neurology.org. From the University of Toronto (J.M.M.), Canada; Rush University Medical Center (K.S.), Chicago, IL; NIH (V.V.), Bethesda, MD; University of Rochester (B.R.), NY; University of Pennsylvania (G.K.-F.), Philadelphia; University of Maryland (K.A., L.M.S., W.J.W.), Baltimore; and University of Kansas (G.G.), Kansas City. Quality Standards Subcommittee Members are listed in appendix E-4 on the Neurology Web site at www.neurology.org. Approved by QSS July 30, 2005; Practice Committee December 15, 2005; Board of Directors February 23, 2006. Endorsed by the National Parkinson Foundation and the Parkinson’s Disease Foundation. Disclosures are provided after the text. Received September 9, 2005. Accepted in final form February 16, 2006. Address correspondence and reprint requests to the American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116. 996 Copyright © 2006 by AAN Enterprises, Inc. This guideline provides answers to the following questions: 1. In patients with PD, what are the most accurate tools to screen for depression, psychosis, and dementia? 2. In patients with PD, what are the best treatments for depression and psychosis? 3. What is the most effective treatment of dementia in PD or dementia with Lewy bodies (DLB)? Background and justification. PD is the second most common neurodegenerative disease.1 Characterized by the cardinal signs of bradykinesia, rigidity, tremor at rest, and abnormalities of balance, posture, and gait, the etiology of PD remains unknown in most patients.2 Nonmotor symptoms in PD, an increasingly recognized intrinsic feature of PD, may affect three domains: autonomic, neuropsychiatric, and sensory, including pain.2 The prevalence of nonmotor symptoms is high. For instance, a survey of 99 patients with PD using validated questionnaires for nonmotor symptoms including anxiety, depression, sensory disturbance, fatigue, or sleep problems revealed that 88% of patients had at least one nonmotor symptom and 11% had five nonmotor symptoms.3 With improved treatment of motor symptoms, it is also now evident that the nonmotor features of PD such as dementia, depression, and psychosis may result in significant disability.2,4 Yet, despite the high prevalence and associated disability of nonmotor symptoms in PD, physician recognition of these important clinical features is low.5 Furthermore, many PD symptoms overlap with features of depression and dementia including symptoms of withdrawal, lack of motivation, flattened affect, decreased physical activity, or bradyphrenia, thus confounding the identification of these behavioral and cognitive disorders. It should be noted that validated criteria for depression, psychosis, and dementia in PD do not exist. Hence, the identification of clinically relevant screening and diagnostic tools for depression, psychosis, and cognitive decline validated specifically in the PD population is necessary. In this parameter, the focus in the section on validation studies will be on the diagnostic accuracy of specific measures for behavioral disorders and dementia in PD. The mechanisms underlying nonmotor symptoms are poorly understood, and may be related to abnormalities of dopaminergic, serotonergic, adrenergic, cholinergic, and other peptidergic pathways.6-9 This complex pathophysiology reflects the resistance of nonmotor symptoms to dopamine replacement strategies. Therefore, specific treatments for autonomic, behavioral, and cognitive complications need to be employed. Converging evidence suggests that the behavioral symptoms in PD may be pathophysiologically different from the behavioral symptoms observed in the general population. For instance, several lines of evidence suggest that PD depression may be related to the underlying pathology of PD itself rather than general psychiatric vulnerabilities and psychosocial associations. This suggests that reliance on the psychiatric treatment literature in the general population may not be sufficient and that specific treatment studies are required in PD. The etiology of dementia in PD is unclear. Whether PD dementia represents a discrete categorical entity from DLB or exists on a spectrum is not known. For the purposes of this parameter, we will consider the treatments of both entities, presuming a similar underlying pathophysiology.10 Throughout this parameter, the term depression will be used to refer to major depression unless otherwise specified; there are no validation or treatment studies investigating forms of depression such as dysthymia or minor depression. This parameter reviews the available evidence assessing diagnostic screening tools and the most effective treatments for dementia, depression, and psychosis in PD. Description of the analytical process. The QSS of the American Academy of Neurology (AAN) identified a panel of six experienced movement disorder specialists, two psychiatrists, and a general neurologist with methodologic expertise. For the literature review, the following databases were searched: MEDLINE, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews and Health and Psychosocial Instruments from 1966 to 2004. This was followed by a secondary search using the bibliography of retrieved articles and knowledge of the expert panel. Two authors reviewed each abstract for topic relevance. Two authors reviewed each full article to rate the level of evidence (Class I–IV) (appendices E-1 and E-2 on the Neurology Web site at www. neurology.org). If there was disagreement, the entire panel reviewed the article and the level of evidence was decided by consensus. The panel reviewed all articles cited in the evidence below. If a panelist was an author of one of the articles, at least two other panelists reviewed that article. Conflicts of interest were disclosed according to AAN guidelines. The AAN provided support and the Michael J. Fox Foundation funded the writing meetings. Panelists were not compensated. Description of literature review. Search terms. Psychosis scale OR depression scale OR psychosis diagnosis OR depression diagnosis OR psychosis treatment OR depression treatment OR cognitive treatment OR dementia diagnosis OR psychoses OR hallucinations OR psychotic OR delusion OR depression OR depressive disorder OR adjustment disorder OR experimental drug therapy OR dementia treatment AND Parkinson disease OR diffuse Lewy body disease OR dementia with Lewy bodies. Inclusion and exclusion criteria. For depression scales and treatment, Diagnostic and Statistical Manual (DSM) criteria for depression were the gold April (1 of 2) 2006 NEUROLOGY 66 997 standard. DSM-IV criteria for major depression were used unless otherwise stated in the study reviewed. Various criteria for the diagnosis of PD were allowed. Class IV studies were not considered if Class III studies were available. Similarly, Class III studies were not considered if Class II studies were available. All Class I and II studies were included. Depression screening tools. The search identified 37 articles. Thirty-four were rejected; 31 did not examine diagnostic accuracy and in 3 the patients did not have PD. Three articles were accepted (Class I, Class II). Depression treatment (pharmacologic). The search identified 31 articles. Twenty were excluded because the populations studied were not PD patients with depression. Two were excluded because they were not randomized controlled trials. Nine articles were reviewed. An additional 27 articles were identified, 19 of which had been identified through the Cochrane bibliography. Of the 36 articles reviewed, 30 were rejected as they were Class IV articles. Six articles were accepted that were Class I, II, or III. Depression treatment (nonpharmacologic). The search identified six studies: one Class II and five Class IV because of a high risk of bias. Class IV studies were not considered. One Class II study was accepted. Psychosis screening tools. The search identified 31 articles. Eighteen did not examine diagnostic accuracy. Twelve articles did not include patients with PD. One Class IV article was accepted. Psychosis treatment. The search identified 63 articles. Twenty-five were rejected because the patients did not have PD. Fifteen were rejected because the articles did not address psychosis treatment. Twenty-three articles received a full review. Eleven were rejected because they were Class III or IV. Three did not include patients with PD. Three were excluded because they were review articles, and one was excluded because it was an epidemiologic study. Four Class I and II articles were accepted. Cognitive screening tools in PD. Twenty-four studies were identified. Ten were rejected because they did not examine diagnostic accuracy. One did not include patients with dementia. Thirteen articles received a full review; five did not examine diagnostic accuracy, five were Class IV, and one did not include PD patients with dementia. Two articles were accepted (Class I, III). Cognitive treatment in PD or dementia with Lewy bodies. The search identified 331 articles. A total of 146 were excluded because they did not include patients with PD. A total of 115 were not randomized controlled trials. Forty-eight did not examine treatment for dementia. Twenty-two articles received a full review. An additional article was identified by the panelists and reviewed. Ten were Class III or IV. Five were excluded because they were review articles, and two articles were excluded because they included PD patients without dementia or criteria for dementia were not adequately defined. Three did not include cognitive treatment in PD. Three Class II articles were accepted. Analysis of evidence. Question 1a: In patients with PD, which are the most accurate tools to screen for depression? Evidence. One Class I and two Class II articles compared the accuracy of depression screening tools to an independent reference standard based upon DSM criteria.11-13 These studies reported results of the Beck Depression Inventory (BDI),11 which is a self completion questionnaire (21 items, range 0–63), the Hamilton Depression Rating Scale (HDRS-17) (17 items, range 0–52),12,13 and the Montgomery Asberg Depression Rating Scale (MADRS) (10 items, range 0–60).12 Both the HDRS-17 and MADRS require a trained administrator and take 15 to 25 minutes each to administer. No studies examining the diagnostic accuracy of the Geriatric Depression Scale, Hospital Anxiety and Depression Scale, or Zung Self-Rating Depression Scale were