Transcript Presentation Slides - American Academy of Neurology

Practice Parameter: Evaluation
and Treatment of Depression,
Psychosis and Dementia in
Parkinson Disease:
An Evidence-Based Review
American Academy of Neurology
Quality Standards Subcommittee
J. Miyasaki, MD; K. Shannon, MD; V. Voon, MD; B. Ravina, MD;
G. Kleiner-Fisman, MD; K. Anderson, MD; L.M. Shulman, MD;
G. Gronseth, MD; and W.J. Weiner, MD
© 2006 American Academy of Neurology
The AAN develops these presentation
slides as educational tools for
neurologists and other health care
practitioners. You may download and
retain a single copy for your personal use.
Please contact [email protected] to
learn about options for sharing this
content beyond your personal use.
© 2006 American Academy of Neurology
Presentation Objectives
• Review background information on
depression, psychosis, and dementia
• Make evidence-based recommendations
for patients with Parkinson Disease (PD)
© 2006 American Academy of Neurology
Overview
•
•
•
•
Descriptive epidemiology
Background and gaps in care
AAN guideline process
Screening tools and treatments
– Depression
– Psychosis
– Dementia
• Summary
• Recommendations for future research
© 2006 American Academy of Neurology
Descriptive Epidemiology of
Parkinson Syndrome
• Incidence
– 5–24/105 worldwide (ref)
– 20.5/105 USA (ref)
• Prevalence
– 57–371/105 worldwide (ref)
– 300/105 USA/Canada (Strickland & Bertoni,
2004)
– Prevalence of PS/PD rising slowly with aging
population
© 2006 American Academy of Neurology
Background
• Nonmotor symptoms an increasingly
recognized feature in PD
– High prevalence
• Affect autonomic, neuropsychiatric, and
sensory domains (Factor & Weiner, 2002)
– May result in significant disability
© 2006 American Academy of Neurology
Background
• Prospective survey n=99 (Shulman et al.,
2001)
– 88% had at least one of
• Anxiety, depression, sensory disturbance, fatigue,
pain, or sleep disturbance
– 11% had 5 or more
© 2006 American Academy of Neurology
Gaps in Care
• Low physician recognition of nonmotor
features in PD
• Many PD symptoms overlap with features
of depression and dementia
• Validated criteria for depression,
psychosis and dementia in PD do not exist
© 2006 American Academy of Neurology
Seeking Answers
• How do we find the answers to the
questions that arise in daily practice?
• In order to keep up to date, need to read
29 articles a day, 365 days a year
(Didsbury, 2003)
• Or find someone who has found and
summarized the relevant data for you
© 2006 American Academy of Neurology
American Academy of
Neurology Guideline Process
Clinical Question
Evidence
Conclusions
Recommendations
© 2006 American Academy of Neurology
Clinical Question
• Question should address an area of
quality concern, controversy, confusion, or
variation in practice
• Question must be answerable with
sufficient scientific data
– Potential to improve clinical care and patient
outcomes
© 2006 American Academy of Neurology
Literature Search/Review:
Rigorous, Comprehensive, Transparent
Complete
Search
Review abstracts
Review full text
Select articles
Relevant
© 2006 American Academy of Neurology
AAN Classification for
Evidence
• All studies rated Class I, II, III, or IV
• Therapeutic Studies
– Randomization, control, blinding
• Diagnostic Studies
– Comparison to gold standard; spectrum
• Prognostic Studies
© 2006 American Academy of Neurology
AAN Level of
Recommendations
• A = Established as effective, ineffective, or
harmful for the given condition in the specified
population
• B = Probably effective, ineffective, or harmful for
the given condition in the specified population
• C = Possibly effective, ineffective, or harmful for
the given condition in the specified population
• U = Data is inadequate or conflicting; given
current knowledge, treatment is unproven
© 2006 American Academy of Neurology
AAN Level of
Recommendations
• A = Requires two consistent Class I
studies
• B = Requires one Class I study or two
consistent Class II studies
• C = Requires one Class II study or two
consistent Class III studies
• U = Studies not meeting criteria for
Class I through Class III
© 2006 American Academy of Neurology
Clinical 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)?
© 2006 American Academy of Neurology
Methods
• Literature Search:
– MEDLINE, EMBASE, CINHAL, and Cochrane
Database of Systematic Reviews, and Health
and Psychosocial Instruments (1966–2004)
• Secondary search using bibliography of
retrieved articles and knowledge of expert
panel
• At least two authors reviewed each full
article
© 2006 American Academy of Neurology
Methods
• Risk of bias determined using the
classification of evidence for each study
(Class I–IV)
• Strength of practice recommendations
linked directly to level of evidence
(Level A–U)
• Conflicts of interests disclosed
© 2006 American Academy of Neurology
Literature Search/Review of
Entire Guideline
523 articles
Exclusion criteria:
-Class IV not
considered if Class III
studies available
-Class III studies not
considered if Class II
studies available
20 articles
© 2006 American Academy of Neurology
Clinical Question 1
In patients with PD, what are the most
accurate tools to screen for depression,
psychosis, and dementia?
© 2006 American Academy of Neurology
Depression Screening Tools
© 2006 American Academy of Neurology
Depression in PD
• Supporting endogenous etiology
– Precede motor symptoms
– More prevalent in PD than other chronic
illnesses
– Not necessarily correlated with severity of
disease
© 2006 American Academy of Neurology
Depression Characteristics
•
•
•
•
•
•
Less guilt
Less risk suicide
Bradyphrenia vs psychomotor slowing
Loss of appetite
Sleep disturbance
Feelings of worthlessness
© 2006 American Academy of Neurology
Clinical Question 1a:
In patients with PD, what are the most
accurate tools to screen for depression?
© 2006 American Academy of Neurology
Depression Diagnosis
• No clear criteria for PD
• DSM IV
–
–
–
–
–
–
–
–
–
Depressed mood most of day, nearly every day
Markedly diminished interest or pleasure in all or most activities
Significant weight loss
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue
Feelings of worthlessness
Inability to concentrate or indecisiveness
Recurrent thoughts of death
© 2006 American Academy of Neurology
Depression Screening
• Beck Depression Index I (BDI-1)
– Self completed
– 21 items
– >13
• www.beckinstitute.org
© 2006 American Academy of Neurology
Depression Screening
• Hamilton Depression Rating Scale
(HDRS)
– Physician administered
– Requires about 20 minutes
– 17 items
– >13
© 2006 American Academy of Neurology
Depression Screening
• Montgomery Asberg Depression Rating
Scale (MADRS)
– 10 items requires 20–25 min
– >14
© 2006 American Academy of Neurology
Literature Search/Review for
Depression Screening
37 articles
Exclusion Reasons:
-Did not examine
diagnostic accuracy
-Patients did not
have PD
3 articles
© 2006 American Academy of Neurology
Recommendations for
Depression Screening
• BDI-1 and HDRS should be considered for
depression screening in PD (Level B)
• MADRS may be considered for depression
associated with PD (Level C)
• Cannot recommend one screening test
over the other
© 2006 American Academy of Neurology
Recommendations for
Depression Screening
• Insufficient evidence to support or refute
the usefulness of other rating scales for
depression in PD (Level U)
© 2006 American Academy of Neurology
Psychosis Screening Tools
© 2006 American Academy of Neurology
Psychosis in PD
• Often a marker of dementia
• Although associated with the treated state,
resolving psychosis often reveals
significant cognitive decline
• Marker for nursing home placement
© 2006 American Academy of Neurology
Clinical Question 1b
In patients with PD, which are the most
accurate tools to screen for psychosis?
© 2006 American Academy of Neurology
Psychosis Screening
• No gold standard for diagnosis of
psychosis in PD
• Hallucinations, delusions, agitation, and
hostility (Chou et al., 2005)
© 2006 American Academy of Neurology
Psychosis Screening
• Parkinson Psychosis Rating Scale
• Not validated in all PD – only psychotic PD
• Good correlation with Brief Psychosis Rating
Scale (BPRS) and Nurses’ Observation Scale
for Inpatient Evaluation (NOSIE) –
– Psychosis items
•
•
•
•
•
•
Visual hallucinations
Illusions/misidentification of persons
Paranoia
Sleep disturbance (RBD)
Sexual preoccupation
Clinical Global Impression
© 2006 American Academy of Neurology
Literature Review for
Psychosis Screening
31 articles
Exclusion Reasons:
-Did not examine
diagnostic accuracy
-Did not include
patients with PD
1 article
© 2006 American Academy of Neurology
Recommendation for
Psychosis Screening
• No recommendation made for psychosis
screening in PD
– No validated psychosis scales
– Psychosis in PD characterized by
• Hallucinations
• Paranoid delusions, delusions of spousal infidelity
• Classification of RBD unclear
© 2006 American Academy of Neurology
Dementia Screening Tools
© 2006 American Academy of Neurology
Dementia in
Parkinson Disease
• 4x risk of age matched controls
• Diagnosis may be late due to masking by
bradyphrenia and loss of motivation
• Hallucinations correlated with dementia
© 2006 American Academy of Neurology
Clinical Question 1c
In patients with PD, which are the most
accurate tools to screen for dementia?
© 2006 American Academy of Neurology
Literature Review for
Dementia Screening
24 articles
Exclusion Reasons:
-Did not examine
diagnostic accuracy
-Did not include
patients with
dementia
2 articles
© 2006 American Academy of Neurology
Recommendations for
Dementia Screening Tools
• The Mini-Mental State Examination
(MMSE) and the Cambridge Cognitive
Examination (CAMCog) should be
considered as screening tools for
dementia in patients with PD (Level B)
• Insufficient evidence to support or refute
the use of EEG as a screening tool
(Level U)
© 2006 American Academy of Neurology
Dementia Screening Tools
• MMSE (Hobson, 1999)
– >25 normal MMSE
– Shorter than CAMCog
– As sensitive
– Less specific
© 2006 American Academy of Neurology
Clinical Question 2:
In patients with PD, what are the best
treatments for depression and psychosis?
© 2006 American Academy of Neurology
Depression Treatment
© 2006 American Academy of Neurology
Clinical Question 2a:
In patients with PD, what is the best
pharmacologic treatment for depression?
© 2006 American Academy of Neurology
Literature Search/Review for
Depression Treatment (Pharmacologic)
31 articles
Exclusion Reasons:
-Populations of PD
without depression
-Not randomized
controlled trials
-Class IV articles
6 articles
© 2006 American Academy of Neurology
Depression Treatment
• Class I study (Wermuth L, Sorensen P,
et al.,1998)
• Citalopram vs placebo
• 6 weeks
• No benefit but underpowered
– Evidence is unclear about the benefit of
citalopram for depression associated with PD
© 2006 American Academy of Neurology
Depression Treatment
• Class II study (Leentjens AF et al.,
2002)
• Amitriptyline – benefit in mod to severe
depression (allocation not concealed)
• Sertraline – no benefit - underpowered
© 2006 American Academy of Neurology
Recommendations for
Depression Treatment
• Amitriptyline may be considered for
depression associated with PD (Level C)
– Not necessarily the first choice for treatment
• Insufficient evidence to make
recommendations for other pharmacologic
depression treatments in PD (Level U)
© 2006 American Academy of Neurology
Clinical Question 2b:
In patients with PD and depression, what
are the best nonpharmacologic
treatments?
© 2006 American Academy of Neurology
Literature Search/Review for
Depression Treatment (Nonpharmacologic)
6 articles
Exclusion Reasons:
-High risk of bias
-Class IV articles
1 article
© 2006 American Academy of Neurology
Recommendations for
Depression Treatment (Nonpharmacologic)
• One Class II study downgraded to Class III
– Underpowered
– Absense of placebo comparison group
• Insufficient evidence to support or refute the
efficacy of transcranial magnetic stimulation or
ECT (Level U)
– All Class IV evidence
© 2006 American Academy of Neurology
Psychosis Treatment
© 2006 American Academy of Neurology
Clinical Question 2c
In patients with PD and psychosis, what is
the best treatment?
© 2006 American Academy of Neurology
Literature Search/Review for
Psychosis Treatment
63 articles
Exclusion Reasons:
-Did not address
psychosis treatment
-Did not include
patients with PD
-Review articles
4 articles
© 2006 American Academy of Neurology
-Class III and Class
IV articles
Psychosis Treatment
• Class I
– Clozapine superior to placebo
– BPRS, CGI, SAPS (PSG, 1999)
• Class II
– Clozapine vs quetiapine
– Both improved psychosis (Morgante 2002)
© 2006 American Academy of Neurology
Psychosis Treatment
• Class II
– Olanzapine vs placebo
– Psychosis did not improve
– Parkinsonism worsened (Breier, 2002; Ondo,
2002)
© 2006 American Academy of Neurology
Psychosis Treatment
• Clozapine
– Baseline ECG, LFT. Absolute neutrophil count
– Weekly neutrophil count x 6 months
– Q2weekly x 6 months
– 12.5 mg qhs x 1 week
– 12.5 mg bid x 1 week etc
© 2006 American Academy of Neurology
Recommendations for
Psychosis Treatment
• For patients with PD and psychosis
– Clozapine should be considered (Level B)
– Quetiapine may be considered (Level C)
– Olanzapine should not be routinely
considered (Level B)
• Worsens motor function
© 2006 American Academy of Neurology
Psychosis Treatment
• Clozapine use
– Associated with agranulocytosis that may be
fatal
– Absolute neutrophil count must be monitored
– Monitoring requirements may vary by country
© 2006 American Academy of Neurology
Clinical Question 3
What is the most effective treatment for
dementia in PD or dementia with Lewy
bodies (DLB)?
© 2006 American Academy of Neurology
Literature Review for
Dementia Treatment
331 articles
Exclusion Reasons:
-Did not include patients
with PD
-Not randomized
controlled trials
-Did not examine
dementia treatment
-Review articles
3 articles
© 2006 American Academy of Neurology
-Included patients
without dementia
-Criteria for dementia not
adequately defined
Recommendations for
Dementia Treatment
• Donepezil should be considered for the
treatment of dementia in PD (Level B)
– Magnitude of benefits is modest
• Rivastigmine should be considered for the
treatment of dementia in PD or DLB
(Level B)
– Magnitude of benefits is modest
– Tremor may be exacerbated
© 2006 American Academy of Neurology
Summary
• Screening tools available for depression
and dementia in patients with PD, but
need more specific, validated tools
• No widely used, validated tools for
psychosis screening in PD
© 2006 American Academy of Neurology
Summary
• Clozapine successfully treats psychosis in
PD
• Cholinesterase inhibitors effective in
treating dementia in PD, but improvement
is modest and motor side effects may
occur
© 2006 American Academy of Neurology
Recommendations for
Future Research
• Depression
– Determination of the most sensitive, specific
and practical depression screening tools for
patients with PD
– Need for randomized, double-blinded,
placebo-controlled studies to assess
antidepressants, psychotherapies, and other
somatic therapies (i.e. ECT and TMS)
© 2006 American Academy of Neurology
Recommendations for
Future Research
• Psychosis
– Evaluation of the PPRS in non-psychotic and
psychotic patients with PD
– Identification of alternatives to clozapine
treatment
– Need for Class I studies to evaluate the
efficacy of quetiapine
© 2006 American Academy of Neurology
Recommendations for
Future Research
• Dementia
– Development of an appropriate scale that
reliably incorporates executive function into a
screening test for PD dementia
– More Class I studies to assess the role of
cholinesterase inhibitors and other
medications in the treatment of dementia
associated with PD
© 2006 American Academy of Neurology
To access the full guideline please visit:
AAN.com/Guidelines
Neurology® April 11, 2006 vol. 66 no. 7;996-1002
© 2006 American Academy of Neurology
Questions, Comments?
© 2006 American Academy of Neurology
Thanks for your participation!
© 2006 American Academy of Neurology