Neuropsychiatric Aspects of Parkinsons Disease: Across the stages - - PowerPoint PPT Presentation

Neuropsychiatric Aspects of Parkinson’s Disease: Across the stages

Iracema Leroi MD FRCPC MRCPsych University of Manchester Manchester Mental Health and Social Care Trust

Parkinson’s Disease in the 21st century: Non-motor symptoms (‘NMS’)

• Pain syndromes
• Parathesias
• RLS
• Fatigue
• Skin symptoms

– Seborrhoea – facial oiliness

• Dysautonomia

– bladder instability, – altered thermal regulation – orthostatic hypotension Prof Ray Chaudhuri

Other non-motor PD features

žPsychiatric Symptoms

› depression › anxiety › sleep disturbance › psychosis

žCognitive Symptoms

› executive dysfunction › mild cognitive impairment in PD (MCI-PD) › dementia in PD (PDD)

Prof Dag Aarsland

The Stages of Symptoms in PD

• Pre-motor stage
• (Prodromal stage)
• Early motor stage
• Moderate motor stage
• Advanced stage

Non-motor symptoms correspond to the orderly progression of LB pathology (Braak stages)

• olfactory bulb
• Dorsal motor nucleus of the

vagus nerve (DMNX)

• Rostral along brain stem

– Locus coeruleus – Dorsal raphe nucleus

• Midbrain substantia nigra

The motor and cognitive stages of PD

PRE-MOTOR EARLY-MOD ADVANCED

PD-mild cognitive impairment Dementia in PD PD normal cognition

Most commonly reported neuropsychiatric symptoms

(in over 20% of each group, excluding sleep & appetite) PD NC PD MCI

PDD

In order of frequency Anxiety Depression Anxiety Depression Apathy Anxiety Depression Apathy Aggress/agitat Hallucinations Delusions Aberrant motor Worsening cognition

Impact of NPS associated with cognitive impairment in PD

Manchester Study on QoL and disability in PD with cognitive impairment

Leroi et al. (2012)

• Impact of cognitive

stage in PD on QoL & disability

• PD-NC (n=54)
• PD-MCI (n=48)
• PDD (n=25)

QOL

Disability

PD-MCI PDD

A g i t a t i

• n

P s y c h

• s

i s A p a t h y A p a t h y

How can we measure NPS in PD?

Neuropsychiatric Inventory (NPI)

• Cummings et al., 1997
• 10 or 12-item scale to measure psychiatric complications
• Informant-reported
• Gold standard in dementia
• Each domain rated as: YES/NO (presence/absence)
• If YES, severity assessed: by Frequency (F) x Severity (S)
• FxS = total score per item (min 0; max 12; clinically significant

≥4)

• Can rate all 10 (or 12) domains OR use a single domain alone

e.g apathy

Neuropsychiatric Inventory: Domains

• Delusions
• Hallucinations
• Depression/dysphoria
• Irritability
• Agitation/aggression
• Euphoria/elation
• Apathy
• Anxiety
• Disinhibition
• Aberrant motor behaviour
• Sleep
• Appetite

Early motor stage of PD

Early PD stage: Psychiatric symptoms

• Depression
• Anxiety more prevalent and severe

– Psychological reaction to the diagnosis

• Sleep

– insomnia (immobility-related)

• Medication side effects (GI, sleep)

Mood disturbances in PD

Early motor stage depression

–Very common…up to 35% pp –Also may be prodrome (1 to 2 years) –May be relieved by initiation of PD medications –Depression is not related to motor symptoms OR disease stage –Not related to medication status (unless undertreated) –Sustained

Differential diagnosis of depressive symptoms in PD

Non-depression:

• Drug-induced mood changes

– Drug withdrawal *DAWS...

• Pathological tearfulness
• Dementia
• Apathy/anhedonia
• Delirium
• “Pseudoanhedonia” (lack of emotional expression)

Depression and motor symptoms in PD: later stages

• Motor-related dysphoria:

– Off-period depression and anxiety – Associated with pattern of on/off syndrome – Other non-motor symptoms present (urinary problems, confusion, pain, panic) – Improves with better motor control

Tips to diagnosis of depression in PD

• 1. Consider collateral sources
• 2. Work-up for reversible causes

–FBC, TSH, testosterone levels, B12, folate –Dementia, delirium, medical illness

• 3. Diagnostic criteria
• 4. Screening Tools

Diagnostic Criteria for Major Depression: DSM-IV or V

• Depressed mood or

anhedonia ≥ 2 weeks

• 5/9 symptoms:
• Depressed

mood/loss of pleasure or interest

• Worthlessness or

guilt, poor concentration

• Suicidal ideation
• Insomnia/hypersomnia
• Psychomotor

retardation or agitation

• Fatigue or loss of energy
• ↓ or ↑ appetite

NINDS/NIMH recommendations for dx of PD-related depression

• Use inclusive diagnostic criteria

– suggest modified DSM-IV criteria – More sensitive than “etiologic/exclusive/substitutional” approach

Depression Rating Scales in PD: MDS Task Force Recommendations

(Schrag et al, 2007)

• Literature review of depression scales
• Expert consensus
• Screening:

– Hamilton depression Scale – Beck Depression Inventory – Hospital Anxiety & Depression Rating Scale – Montgomery-Asberger Depression Rating Scale – Geriatric Depression Scale

• Severity:

– HAM-D, Beck, Zung – Cornell scale (CSDD) needs validating in PD

Pharmacologic Treatment of Depression in PD

• Inadequate evidence:

– inadequately controlled & under-powered trials…but about 1/5 of PwPD take antidepressants

• Elderly population
• Dosing as per “start low, go slow” rule
• Drug-drug interactions with selegiline, (rasagiline)
• Pramipexole (D2,D3) may be useful

Pharmacological Treatment of Depression in PD: Reviews

(Starkstein 2017).

Author # Studies Years Type Conclusion Klaassen et al, 1995 4/12 1966-1993 Meta-analysis Insufficient evidence Movement D/O (supp 4), 2002 5/19 ? Review Insufficient evidence Cochrance 2003 3 RCT (SSRI) 1800s-2001 Review Insufficient evidence Weintraub et al, 2005 27 N=772(668 completers) >80% on SSRI 1965-2003 Meta-analysis & effect size

Large effect size in active & plc groups; larger in non- PD depressed

Classes of Antidepressants for use in PD

SNRI – Venlafaxine, Duloxetine NDRI – Bupropion SSRI – fluoxetine, paroxetine, fluvoxamine, citalopram, escitalopram SARI – trazodone, nefazodone NASA - mirtazepine

Dopamine Agonists as antidepressants in PD?

(Ferreira J 2013)

• RCT of pramipexole for depression in PD (Barone 2010)
• n= 296 patients
• Significant improvement :

– Beck Depression Inventory – Geriatric Depression Scale – UPDRS motor scale – UPDRS ADL

Summary of Opinion of Drug Treatment of depression in PD (McDonald 2010)

• None of the antidepressants have a clear advantage

in terms of efficacy, but the SSRIs are more easily tolerated (Starkstein 2017)

• Older patients may take longer to respond and need

at least a 12 week trial at adequate dose to assess response

• Older patients often need optimal doses to respond

fully

• Treat until remission is reached or relapse risk is high

All-Party Parliamentary Group (APPG) on Parkinson’s inquiry into anxiety and depression in Parkinson’s (2018)

Psychotherapy? (APPG)

• before considering psychotropic medication,

consideration should be given to psychological interventions

• e.g. cognitive behavioural therapy (CBT)

(Dobkin 2006, Troeung 2014).

• brief psychotherapy (CBT and psychodynamic

therapy) has been shown ( Xie 2015) to be effective in helping a proportion of depressed patients with PD….but there is a paucity of evidence.

Severe depression in PD

• can be effective (Borisovskaya 2016) and has

the benefit of transiently improving motor control

• repetitive transcranial magnetic stimulation

to be beneficial and but the evidence is insufficient to recommend this for clinical practice

Anxiety in PD

• estimated point prevalence of all DSM

anxiety disorders in Parkinson’s is around 34%

• may co-occur with depression, worsening

the symptoms (Menza 1993)

• general anxiety disorder (GAD), panic

disorder and social phobia frequently present as separate disorders in Parkinson’s disease

Anxiety in PD

• clinical experience suggests that

anxiety is more prominent than depression when levodopa is wearing off

• anxiety can be particularly intense at

night

Principles of treatment of anxiety in PD

• less is known about the specific

treatment of anxiety in PD than depression

• the same principles of treatment for

depression also apply to anxiety.

Principles of treatment of anxiety in PD

• Address social factors first
• Then, optimise DRT
• Only use antidepressant/anti-anxiety medication if

the response is unsatisfactory

• • depression, urinary symptoms and sleep

disturbances are most likely to influence anxiety …. need for a holistic approach to treatment (Jiang 2015).

Moderate stage: Apathy

Apathy Ratings: PD normal cognition vs PD MCI

(Leroi 2012)

Neuropsychiatric Inventory: Apathy subscale

50 100 150 200 250 300 350 400 Inf orm ant r ated ap ath y PD NC PD MCI PDD *

Apathy Scale (Starkstein)

5 10 15 20 Self- rat ed apat hy PD NC PD MCI * ANCOVA with age and motor severity as covariates: differences remained significant *

Apathy has 3 key dimensions

Apathy is the only NPS that distinguishes PD from MCI-PD

n=91 PwPD EB+ vs EB-

Apathy: emotional blunting

( ↑ indicates worse function)

EB- EB+

Diagnosis of apathy may be difficult

• Overlap with:

– Motor symptoms:

• bradykinesia, “off” states, masked facies

– Depression:

• low mood, anhedonia, low energy

– Cognitive impairment:

• bradyphrenia

– Excessive daytime sleepiness – Fatigue

MDS Task Force on Apathy Rating Scales

(Leentjens et al, 2008)

• Apathy Evaluation Scale (AES)
• Apathy Scale (AS)
• Apathy Inventory (AI),
• Lille Apathy Rating Scale (LARS)
• UPDRS part I, item 4 (motivation/initiative)
• Neuropsychiatric Inventory (NPI), Domain 7 (apathy)
• Only the AS (Starkstein) is classified as

‘Recommended’ to assess apathy in PD

Management of apathy in PD

• No good evidence base

– Case series: modafinil, bupropion, amphetamine- like stimulants

• Associated with lower dopaminergic load (especially

dopamine agonists)

• Treat co-morbid depression
• Consider external stimulation/structure
• Support for caregivers
• Education

Moderate stage: Impulse control disorder (ICDs)

Definition of Impulse Control Disorders (ICDs)

• A spectrum of psychiatric disorders involving

pleasurable or hedonic behaviours

• Person fails to resist the drive to behave in ways that

result in distress or impaired social and occupational functioning

• Behaviours are repetitively, compulsive
• Addictive pattern… “behavioural addiction”

Spectrum of ICDs in PD

• “GSES”
• pathological gambling
• compulsive sexuality
• binge eating
• compulsive shopping
• Affects 8-15% of PD (Weintraub 2010)

– 6% of PD not on DA – 17% on DA

Dopamine Dysregulation Syndrome (DDS)

(Evans 2004; Giovannoni 2000)

• ?extreme end of ICD in PD
• “hedonistic homeostatic

dysregulation”

• “dopamine drug addiction”
• “compulsive dopaminergic drug use”

Punding

• Repetitive, purposeless motor behaviours
• Coined in amphetamine users
• Like stereotypic behaviour of rodents treated

with chronic psychostimulants

• Most often associated with levodopa addiction

and apomorphine use

• Exaggeration of premorbid interests, hobbies or

emerge as new skill (poetic talent, painting)

• Examples: repairing things, gardening, playing an

instrument, excessive computer use, cleaning, model building

ICDs and dopamine therapy

• Iatrogenic complication associated with

dopaminergic replacement therapy in PD

• Total dopaminergic load (LEDD)

– Dopamine agonists (2-3x greater risk) – Levodopa

• Also reported with amantadine, selegiline

Pathophysiology

(Voon 2007; Delaney, Leroi 2012)

susceptibility dopaminergic medications “susceptibility multiplier” ICDs

What are the susceptibility or risk factors for ICD?

Role of susceptibility: Risk factors to develop ICDs

(Voon 2011; Weintraub 2010; Leroi 2011)

• Younger age
• Younger age at PD
• nset
• Male sex
• Not married
• Self-reported family

history of gambling

• ?novelty seeking

personality profile

• Psychosocial factors

“Ventral (limbic) Overdose Hypothesis”

(Cools 2001)

• Ventral striatum: intact projections in younger PD,

get “over-dose” of dopamine when treated with DRT → ICD, impaired reversal learning…

• Dorsal striatum: damaged projections in PD, so

normalises function with DRT → improved executive, working memory, motor function…

Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP)

(Weintraub et al. 2008).

• brief, self-administered screening

questionnaire

• Section 1: compulsive gambling, buying,

sexual behaviour, and eating;

• Section 2: other compulsive behaviours

(hobbyism, punding and walkabout);

• Section 3: compulsive medication use (DDS)

Management of ICDs in PD

• Prevention
• Intervention:

– 3 key nodes

• 1. dopamine replacement therapy
• 2. psychological distress
• 3. other psychotropic medication

Prevention of ICDs in PD

• Education
• Informing ALL patients for whom dopamine agonists

are prescribed about ICD risk – BNF lists PG, HS and binge eating as AE of DA

• Informing family/carers (with patient permission)

– Consider setting up contract between patient and carers about disclosure of change in behaviours

Prevention of ICDs in PD

• Identify susceptible patients for closer monitoring

and follow-up – Early severe dyskinesias (12-24 into treatment) – Young, male, family history addictions, alcohol dependence

• Prompt and direct screening: consider using a

screening tool

Intervention node 1: Dopamine replacement therapy

• Dose education/stepwise discontinuation of DA
• r most recent DRT (Gallagher 2007; Driver-Dunckley 2003; Dodd

2005)

• Limited long-term outcome data

– ICD have sustained improvement post DA reduction (Mamikonyan 2008)

• Pharmacist intervention:

– blister packs, limited supply of medication, restricted dosing on a daily basis

Intervention node 1: Dopamine replacement therapy

• Switch to a different class of DA …may cause ICD

relapse

• Longer acting DRT formulations
• Duodopa
• Deep brain stimulation (Ardouin 2006)

*Caution: Dopamine agonist withdrawal syndrome (“DAWS”)

Intervention node 2: Address psychological distress

• Education for patient and family

– Developing awareness

• Supportive psychotherapy

– Help line contact – Contact with other sufferers (user-carer groups) – Frequent contact and monitoring with PD team

• Cognitive behaviour therapy

Intervention node 2: Address psychological distress

• Addiction support groups

– remission only on DA reduction + Gambler’s anonymous (Kurlan 2004) – n=15 long-term f/up – n=4 only achieved partial remission with GA attendance as well (Mamikonyan 2008)

Intervention node 2: Address psychological distress

• Identify and treat psychiatric comorbidities
• Depression
• Anxiety
• Watch out for trigger a manic-like episode with

antidepressants

Intervention node 3: Alternative pharmacological therapies

• Caution: publication bias for treatments
• Atypical antipsychotics…olanzapine & quetiapine for

hypersexuality

• SSRI: paroxetine in non-PD PG (Kim 2002)
• Fluvoxamine in non-PD PG (Hollander 2000)
• Naltrexone (opioid antagonist) in non-PD PG (Grant

2008);

• Amantadine: RCT: n=17 PD with PG suggested

improvement with this (Thomas 2010)

• Zonisamide: Open non-randomised trial (Bermejo 2010)

Advanced stage PD: Psychosis

• #1 factor in nursing home placement
• Major source of caregiver burden
• Associated with increased mortality

Psychosis in PD

Psychosis in PD

(Fenelon et al, 2000)

Passage hallucinations:

• seeing something passing-

by oneself for a fleeting moment Presence hallucinations:

• the feeling that someone

is present in the room Illusions:

• mistaking an object for an

animal or person Complex hallucinations:

• seeing, hearing, feeling or

smelling something that is not really there

Examples of passage illusions

(slide compliements of D. Whitehead)

A: ‘I kept seeing these ants

• n the carpet ...

crawling about...When I was reading in the evening they were there, but I couldn’t find them..... I put down powder, but they were still there of course!’ Pt B: ‘In the mornings I feel as though there’s two of us. I can’t phrase it very well ... as though we’re side by side, going up the stairs... Very peculiar it is !’

Delusions in PD

– Delusions of spousal infidelity (Othello syndrome) – Often accompany hallucinations – Other persecutory delusions

Management of psychosis in PD

• Rule out reversible factors or triggering events
• Decrease PD meds and remove key culprits
• Levodopa is removed last
• If cognitive impairment is present, consider

starting with a cholinesterase inhibitor (e.g. rivastigmine)

RCTs of Cholinesterase Inhibitors in PDD

Emre et al 2004, N=541:

– Oral rivastigmine v placebo – significant but modest overall improvement in neuropsychiatric symptoms.

• Burn et al 2006, Sub-group analysis of the Emre study,

N=188 participants wth visual haluicnations

– No specific benefit in visual hallucination sub-score

• Dubois et al 2012 N=550: Oral donepezil v placebo

– Less convincing overall benefits – No specific benefits in neuropsychiatric symptoms

Antipsychotics for psychosis in PD?

Off-Label Antipsychotic Use for PD Psychosis

• Used despite interference with motor function and Significant safety

concerns

– ~135,000 patients with PD psychosis are currently treated with off-label antipsychotics

• Dopamine D2 receptor antagonists worsen PD mobility1
• Increased mortality risk in PD2
• Adverse effects especially problematic in PD patients1,2

– Somnolence (histaminergic H1 antagonism) – Orthostatic hypotension (adrenergic alpha-1 antagonism) – Constipation, dry mouth (muscarinic antagonism) – Drooling, dysphagia, cognitive impairment – Neuroleptic sensitivity, neuroleptic malignant syndrome – Metabolic syndrome, cerebrovascular events, seizures – Leukopenia, neutropenia, agranulocytosis

• 1. Goldman JG, Holden S. Curr Treat Options Neurol. 2014;16(3):281. 2. Weintraub D, et. al. JAMA. 2016 (in press)

Atypical Antipsychotics Clozapine 2 RCTs Both RCTs small and only 4 weeks duration (n=60) show significant benefit in psychosis (Cohen’s d 0.8) without worsening of motor symptoms. Possible increase of deaths in 1 study. Black box warning for agranulocytosis with mandatory monitoring. Risperidone Limited evidence from

• pen clinical

trials Parkinsonian side effects too severe to consider in clinical practice Olanzapine 2 RCTs Worsening of motor symptoms too severe for olanzapine to be a viable treatment Quetiapine 5 RCTs 3/4 RCTs in people without dementia and the only RCT in people with dementia indicated no benefit in the treatment of psychosis. The other study was small and showed mixed results.

Treatment of Psychosis in PD, PDD, DLB

Friedman et al 2010, Aarsland et al 2012

Antipsychotics for psychosis in PD

• Add an antipsychotic if symptoms only if:

– symptoms cause distress – Safety concerns (e.g. aggressive to carer) – Intolerable motor worsening on reduction of dopamine replacement

• Avoid typical antipsychotics (e.g. haloperidol)
• Atypical antipsychotics are preferred but:

– Avoid risperidone ...limited by motor effects – Avoid olanzapine...limited by motor effects and limited efficacy ...avoid in PD

• Consider quetiapine: may have a role but caution with

side effects

Clozapine for psychosis in PD

• atypical antipsychotic with little effect on motor

symptoms

• Specific license for psychosis in PD
• Use only for significant psychosis in which other

interventions have not been effective

• 6.25mg start

Clozapine for psychosis in PD

• Key problem:

–agranulocytosis – weekly monitoring of WBC for fist 6 months; can get sudden or gradual drop in WBC –sialorrhea –delirium –GI disturbances –seizures in 4% (dose related)

When to avoid antipsychotics: Too good or too bad…

• Clear sensorium with good insight
• Symptoms do not cause distress
• Caution if:

– established dementia

• Increased risk of CVA in

dementia

• Increased mortality
• Increased cognitive

impairment

– advanced motor symptoms

• EPSE

– Significant non-motor symptoms

• Hypersalivation
• Falls/dizziness
• Weight loss
• constipation

• 020 Study: Pimavanserin Demonstrated Highly

Significant Antipsychotic Efficacy (Lancet Feb 2014)

79

** *

SAPS-PD (primary endpoint)

(ITT, N=185; change from baseline)

Other potential therapies for VH in PD

• Cholinesterase inhibitors in PD without

dementia

– case series/open studies

• Ondansetron

– Case series/open studies

• Muscarinic agonists

– PM studies in DLB/PDD show association between reduction of M1 receptors and delusions, M2/M4 – Previous study of Xanolamine in AD suggested improvement in psychosis – New muscarinic agonists with better tolerability profiles moving into clinical trials

Management of specific visual hallucinations

ffytche DH. Dialogues Clin Neurosci 2007 ffytche DH. Curr Opin Neurol 2009

• Reassurance
• Education
• Patient support groups
• Ophthalmological Rx
• Visual strategies

Further investigations if mismatch between hallucinations and clinical context Persistent, distressing (Negative outcome CBS)

• Review anti-cholinergic load
• Exclude concurrent infection / delirium
• Optimise vision

Medication Psychological

• Cholinesterase inhibitor
• Anti-epileptic
• Citalopram
• (Atypical antipsychotic)
• Counselling
• CBT

? Neurophysiological

• rTMS / tDCS

Let’s get political…

Accessing mental health services for PD (APPG 2018)

The majority of mental health problems in Parkinson’s disease are not optimally managed with 30% remaining untreated (Dobkin 2013).

What are the barriers to accessing mental health support for people with Parkinson’s ?

Discuss….

Barriers to accessing mental health services for PD ‘ ‘Institutionalised dualism’

• a system of institutional design, language,

politics, training, culture and economics which unhelpfully separates the physical and mental domains.

Barriers to accessing mental health services for PD

• excluded from mental health services on the spurious grounds that “it is a physical

problem not a mental health one”

• PD services have focused on motor rather than non-motor symptoms and there is lack of

recognition of mental health issues (screening and detection) among the health professionals seeing this group of people (Shulman 2002 and Dobkin 2013).

• Physical and mental health commissioning is often done separately so patients must be

referred separately to mental health services or to the GP needs to refer lack of knowledge of who /how to refer to mental health services and the inconsistency of the approach between services (East Midlands survey )

• no commissioned specialist mental health into the Parkinson’s disease clinic.
• separate IT systems and record-keeping systems often between physical and mental

health trust.

• Psychiatric assessment letters are not routinely copied to Parkinson’s disease clinic

services: by convention they are sent only to the relevant GP.

• different lengths of follow up with mental health services having shorter length of input
• difficult to access psychological therapies.

How can the barriers be

• vercome?

Dr Atul Gawande - 2014 Reith Lectures: Why Doctors Fail

Dr Atul Gawande - 2014 Reith Lectures: Why Doctors Fail ..’much of failure in medicine remains not due to ignorance (lack

• f knowledge) but is due to a failure to use existing knowledge..’

• http://www.bps.org.uk/sites/default/files/documents/psychological_services_for_people_with_parkinsons_disease.pdf

Baillon S.; Lindesay J.; Dennis M.( 2014 ) Screening for depression in Parkinson's disease: The performance of two screening questions . Age and Ageing; 2014 ;43 (no. 2): 200-205 Borisovskaya A.; Bryson W.C.; Buchholz J.; Samii A.; Borson (2016) . Electroconvulsive therapy for depression in Parkinson's disease: Systematic review of evidence and recommendations Neurodegenerative Disease Management; 2016; vol. 6 (no. 2); p. 161-176 Chen J.J.; Marsh L , ( 2014 ) Anxiety in Parkinson's disease: Identification and management ( 2014 ) Source Therapeutic Advances in Neurological Disorders; 2014; vol. 7 (no. 1); p. 52-59 Dobkin RD, Menza M, Allen LA, Gara MA, Mark MH, Tiu J, Bienfait KL, Friedman J. ( 2011) Cognitive-behavioral therapy for depression in Parkinson’s disease: a randomized, controlled trial. Am J Psychiatry. 2011;168(10):1066–74. Dobkin, R.D., Allen, L.A. & Menza, M. (2006). A cognitive behavioural treatment package for depression in Parkinson’s disease. Psychosomatics,2006; 47, 259–263. Dobkin, R D.; Rubino, Jade Tiu; Friedman, Jill; Allen, Lesley A.; Gara, Michael A.; Menza, Matthew ( 2013) Barriers to mental health care utilization in Parkinson’s disease Journal of Geriatric Psychiatry and Neurology; 2013; vol. 26 (no. 2); 105-116 Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G, Dietrichs E, Fabbrini G, Friedman A, Kanovsky P, et al. ( 2013) Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s

• disease. Eur J Neurol. 2013;20(1):5–15.

Jiang, Si-Ming; Yuan, Yong-Sheng; Tong, Qing; Zhang, Li; Xu, Qin-Rong; Ding, Jian; Zhang, Ke-Zhong ( 2015) The association between clinically relevant anxiety and other non-motor symptoms in Parkinson’s disease Neurological Sciences; Nov 2015; vol. 36 (no. 11); p. 2105-2109 Menza, M., Defronzo Dobkin, R., Marin, H., Mark, M.H., Gara, M., Buyske, S., Bienfait, K. & Dicke, A. (2009). A controlled trial of antidepressants in patients with Parkinson’s disease and depression. Neurology 2009 Mar 10; 72(10): 886–892. Menza, M., Robertson-Hoffman, D.E. & Bonapace, A.S. (1993). Parkinson’s disease and anxiety: Comorbidity with

• depression. Biol Psychiatry, 1993 34, 465–470.

References: Mental Health in PD

• Richard I.H.; La Donna K.A.; Podgorski C.; Kurlan R.; Hartman R.; Pearson N.; Deeley C.; McDonald W.;

Juncos J.; Sommerfeld B.; Brodsky M.; Barnard M.; Factor S.; Nash J.; Friedman J.; Tobia L.; Marsh L.; Gerstenhaber M.; Shulman L.; Dustin K.; Waters C.; Benabou R.( 2007) . The patients' perspective: Results of a survey assessing knowledge about and attitudes toward depression in Parkinson’s disease Neuropsychiatric Disease and Treatment; 2007; vol. 3 (no. 6); 903-906 Shulman LM, Taback RL, Rabinstein AA, Weiner WJ. ( 2002) Nonrecognition of depression and other non- motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord. 2002;8(3):193-197. Troeung L, Egan SJ, Gasson N. ( 2014) A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson’s disease. BMC Psychiatry. 2014;14:19 Williams J.R.; Goldstein S.R.; Hirsch E.S.; Lehmann S.; Little J.T.; Margolis R.L.; Palanci J.; Pontone G.; Rabins P.; Marsh L.; Grill S.; Weiss H.; Anderson K.; Bush A.L ( 2012) comparison of nine scales to detect depression in Parkinson disease: Which scale to use?. Neurology; Mar 2012; vol. 78 (no. 13); 998-1006 A national clinical guideline. Scottish Intercollegiate Guidelines Network; 2010.Diagnosis and pharmacological management of Parkinson’s disease: A national clinical guideline. Scottish Starkstein, S. E. and Brockman, S. (2017), Management of Depression in Parkinson's Disease: A Systematic Review. Mov Disord Clin Pract. doi:10.1002/mdc3.12507 Xie, Cheng-Long; Wang, Xiao-Dan; Chen, Jie; Lin, Hua-Zhen; Chen, Yi-He; Pan, Jia-Lin; Wang, Wen-Wen (2015) A systematic review and meta-analysis of cognitive behavioral and psychodynamic therapy for depression in Parkinson’s disease patients Neurological Sciences; 2015; vol. 36 (no. 6); 833-843 Report by British Psychological Society on Psychological Services for people with Parkinsons disease http://www.bps.org.uk/sites/default/files/documents/psychological_services_for_people_with_parkins

• ns_disease.pdf

References: Mental Health in PD

[Extra slides]

Current Management of PD Psychosis Suboptimal Reflecting Critical Unmet Need

• Identify triggers of PD psychosis

– Minimize polypharmacy – Treat co-morbid illnesses (e.g., infections)

• Utilize psycho-social interventions
• Reduce, stop, or not increase dopaminergic therapy

– Leads to increased motor symptoms – Psychosis often persists / recurs despite dose reduction

• No FDA-approved medication for PD psychosis

– PD psychosis is often not treated despite progression – Empiric use of off-label antipsychotics is common

Goldman JG, Vaughan CL, Goetz CG. Expert Opin Pharmacother. 2011;12(13):2009-24. Goldman JG, Holden S. Curr Treat Options Neurol. 2014;16(3):281.