PSYCHIATRIC ASPECTS of PSYCHIATRIC ASPECTS of PARKINSON’S DISEASEPARKINSON’S DISEASE

and Related Disordersand Related Disorders

Michael J Kelly MD FRCPCMichael J Kelly MD FRCPC

Grand River Hospital Grand River Hospital Kitchener-WaterlooKitchener-Waterloo

7 May 20087 May 2008

Learning ObjectivesLearning Objectives

Recognize the psychiatric co-morbidities Recognize the psychiatric co-morbidities associated with Parkinson’s Disease and associated with Parkinson’s Disease and related disordersrelated disorders

Better appreciate management of the Better appreciate management of the common neuropsychiatric complications common neuropsychiatric complications

Impact

• The impact of PD on individuals is a wide-ranging as the clinical manifestations of the disease itself

• The disease can make even the most mundane daily activity a challenge

• Most discussion of PD focuses on its motor features, such as tremor, slowness, and imbalance

• Yet the so-called “non-motor” aspects of the illness, depression, anxiety, memory difficulties, sleep disturbances, etc., are often prominent and can cause as much or more difficulty for individuals struggling with the disease

James Parkinson 1817

• “ a more melancholy object I never beheld”

Meds: Friend or Foe?

• Pharmacologic issues regarding appropriate management of the neuropsychiatric aspects are particularly complex

• Some of the medications used to treat PD aggravate neuropsychiatric symptoms

• Agents used to control behavioural disturbances in PD may increase parkinsonism

Treatment Treatment

-

-

Maintain motion

Control emotion

“Motion-Emotion Conundrum”

Behavioural• Behavioural and neuropsychiatric aspects of

PD represent important clinical challenge in optimizing the quality of life of patients and their caregivers.

• Frequently accounts for a substantial portion of the distress associated with the disease, the burden experienced by caregivers, the requirement for institutionalization or nursing home placement.

Associated Psychiatric Features

• Depression• Anxiety• Apathy/abulia• Affective lability (nonmotor fluctuations)• Disinhibtion, mania, gambling, hypersexuality• Agitation• Aggression• Confusion/disorganization/dementia• Delirium• Caregiver strain!

FREQUENCY OF FREQUENCY OF NEUROPSYCHIATRIC SYMPTOMSNEUROPSYCHIATRIC SYMPTOMS

SYMPTOMSYMPTOM FREQUENCY FREQUENCY %%

AnxietyAnxiety 6666

FatigueFatigue 5656

IrritabilityIrritability 5252

HallucinationsHallucinations 4949

Self-withdrawalSelf-withdrawal 4444

EuphoriaEuphoria 4242

Lassitude/wearinessLassitude/weariness 4242

SadnessSadness 3838Witjas T et al. Neurology, 2002;59:408-413.

RISK FACTORS FORRISK FACTORS FORNON-MOTOR COMPLICATIONSNON-MOTOR COMPLICATIONS

•Early age of disease onset•Longer duration of disease•Higher doses of levodopa•Age of patient•Presence of motor fluctuations

Preclinical Parkinson’s Disease

• No specific clinical markers known

• 4-13% of autopsies in elderly showing incidental Lewy bodies are regarded as preclinical cases

• Increased risk of neuroleptic parkinsonism

• Duration of preclinical phase unknown (several years to several decades?)

• PET studies may identify preclinical caseswww.wemove.org

DEPRESSION INDEPRESSION INPARKINSON’S DISEASEPARKINSON’S DISEASE

•Affects 40-50% of patients

•Characterized by:Feeling of guiltLack of self esteemLoss of initiativeHelplessness, remorse, sadness

•Causes may be endogenous, exogenous, or both

Key Features of Depression in PD

• Reported dysphoria/sadness

• Apparent sadness

• Anhedonia

• Exaggerated pessimism

• Suicidal ideation

• Irritability

• Comorbid anxiety

Diagnostic Difficulties• Overdiagnosis; PD

interpreted as depression

- Rigidity

- Masked facies

- Bradykinesia

- Bradyphrenia

- Cognitive impairment

- Insomnia

- Apathy

• Underdiagnosis: - Bradykinesia, masked

facies mask depression - Cognitive impairment - Bradyphrenia - Low voice - Ageism - Lack of attention to

emtional problems

Potential Mechanisms

• Psychosocial stress in general

• Genes

• Comorbidity

• Structural and functional brain changes

• Antiparkinson agents

• Latent psychiatric disease

• Psychological reaction to diagnosis and impairment

Antidepressant, Dopamine, and EPS

• SSRI may induce/worsen parkinsonism

• 5HT/NA agents more effective than SSRI?

• ECT increases dopaminergic activity and may improve depression + parkinsonism*

• Methylphenidate improves depression and apathy in PD?

• Pramipexole improves depression and apathy in PD?

Psychosis in Parkinson’s Disease (PD)

• Major clinical challenge

• Major source of caregiver burden

• #1 factor in nursing home placement

• Associated with increased mortality

• Prognosis improved with advent of atypical antipsychotics

Prevalence of Psychosis

• ~8%-40% reported rates

• Depends on definition of psychosis, Parkinson’s disease (PD), congnitive impairment

• ~5%-17% without significant dementia

• ~42%-81% with significant dementia

General Categories of Psychosis

• Features– Vivid dreams/nightmares, disorientation, hallucinations,

delusional thought

-Visual hallucinations with insight “Benign” psychosis

• Hallucinations and/or delusions without insight

• Hallucinations and/or delusions with delirium

Delusions• ~3%-30% reported prevalence rates• Phenomena -Delusions of spousal infidelity Phantom border - Feature of affective psychosis - Often accompany hallucinations - Other persecutory delusions

Etiology/Risk Factors for Psychosis

• No single explanation

• Most commonly reported cause

- Dopaminergic medications Rare cases before L-dopa

All dopamine agents can elicit psychosis

Reduction in dopamine medications decrease psychosis

Treatment of Psychosis• Step 1: Primary prevention• Step2: Treat medical illnesses • Step 3: Eliminate psychoactive

medication - Benzodiazepines, opiates, H2

Blockers, tricyclic anitpdepressants (TCAs),

antispasmodics• Step 4: Treat comorbid pscyhiatric

illnesses

Treatment of Psychosis

• Step 5: Nonpharmacological strategies • - Education, reassurance,

activity/day programs, placement• Step 6: Eliminate antiparkinsonian

medications• Step 7: Address disrupted sleep• Step 8: Trial of cholinesterase inhibitors • Step 9: Trial of neuroleptic agents

QuetiapineQuetiapine

Most common first-line agentMost common first-line agent6.25-12.5 mg starting dose6.25-12.5 mg starting doseEscalate as needed/tolerated Escalate as needed/tolerated Adverse effectsAdverse effects

- Sedation - Sedation

- Orthostasis - Orthostasis - Confusion - Confusion - Increased parkinsonism, especially with dementia - Increased parkinsonism, especially with dementia - Increased fluctuations - Increased fluctuations

ClozapineClozapine

Most effective agent for psychosis in PD, but use Most effective agent for psychosis in PD, but use avoided because of need for blood monitoring avoided because of need for blood monitoring Dose range: 6.25 mg od ≥ 200 mg/dayDose range: 6.25 mg od ≥ 200 mg/dayStarting dose 6.25 mg qhs Starting dose 6.25 mg qhs Escalate as needed/tolerated Escalate as needed/tolerated Adverse effects Adverse effects

- Sedation - Sedation - Orthostasis - Orthostasis - Confusion - Confusion - Worse parkinsonism- Worse parkinsonism - Agranulocytosis - Agranulocytosis - Seizures - Seizures

Other Strategies to Treat Psychosis

• Cholinesterase inhibitors -Positive results in open-label studies of PD

and Lewy body dementia - Variable tolerance- need to monitor - May still benefit from lower doses

• Electroconvulsive Therapy (ECT) - Especially with psychotic depression

Preventive Strategies

• Evaluate PD regimen for overmedication, inadequate medication, fluctuations

• Address early -Mood disorders - Sleep disorders

Adjust PD medications- 24 hour dopamine needs Trazodone, quetiapine

- Cognitive impairment Cholinesterase inhibitors

? Other Alzheimer’s disease treatments

Sexual Desire and Function• Individual variation in effect of PD

• Some patients have hypersexuality with dopaminergic drugs(Impulse Control Disorders

• Erectile dysfunction

• Other causes of sexual dysfunction– depression– SSRIs– endocrine dysfunction

www.wemove.org

Impulse Control Disorders (ICDs) in PDImpulse Control Disorders (ICDs) in PD

Pathological GamblingPathological Gambling

HypersexualityHypersexuality

Pathological ShoppingPathological Shopping

Compulsive EatingCompulsive Eating

Dopaminergic Medication abuseDopaminergic Medication abuse

Punding Punding

ICDs: General Treatment StrategoesICDs: General Treatment StrategoesAdjust antiparkinsonian treatment Adjust antiparkinsonian treatment

– Reduce dosage of dopaminergic medications Reduce dosage of dopaminergic medications – Change to a different dopamine agonistChange to a different dopamine agonist– Discontinue dopamine agonist Discontinue dopamine agonist

Pharmacologic trials- anecdotal Pharmacologic trials- anecdotal – Quetiapine and clozapine Quetiapine and clozapine – Antiandrogens, valproate, lithium, atomoxetine, treatment Antiandrogens, valproate, lithium, atomoxetine, treatment

of comorbid depression of comorbid depression

Psychosocial supportsPsychosocial supports– Limit access to behaviours Limit access to behaviours – Counseling, psychotherapy, CBT, Gamblers AnonymousCounseling, psychotherapy, CBT, Gamblers Anonymous

SLEEP DISTURBANCES IN SLEEP DISTURBANCES IN PARKINSON’S DISEASEPARKINSON’S DISEASE

•Insomnia

•REM behavior disorder

•Nightmares

•Obstructive sleep apnea

•Excessive daytime sleepiness

COGNITIVE IMPAIRMENT INCOGNITIVE IMPAIRMENT INPARKINSON’S DISEASEPARKINSON’S DISEASE

• Affects up to 40% of patients

• Late feature of PD

• Differential diagnosis: PDD vs AD vs DLB

• Frontal-executive dysfunction, impairments of visuo-spatial abilities, temporal ordering, memory and attention

• Increases caregiver burden

PD with Dementia

DSM-IV Memory impairment

• + 1 or more of praxis, executive functions( planning, abstraction, conceptualization, reasoning ) ,gnosis

• Decline, impair occupational/social fn

• Not delirium• Consequence of

Parkinson’s disease

• Cummings and Benson

• 3/5 domains

• Language• Memory• Complex cognition

( executive functions)• Visuospatial functions• Personality or emotion

Neurodegenerative Disorders with Parkinsonism (I)

• Diffuse Lewy body disease

– Early onset of dementia

– Delusions and hallucinations

– Agitation

www.wemove.org

DLB

• Fluctuating cognition ( attention / arousal / alertness )

• Recurrent visual hallucinations

• Motor features of parkinsonism

• Ofen with repeated falls, syncope, transient loss of conciousness

• Neuroleptic sensitivity, delusions, other hallucinations

DLB vs PDD• Arbitrary “ one year rule “

• DLB- dementia syndrome must occur before or within one year of onset of parkinsonism

• PDD-dementia syndrome evident more than one year after onset of parkinsonism ( actually often occurs as a later stage complication, at least 8-10 years after motor symptoms.)

• Cumulative prevalence of dementia 80% in PD pts with 10+ yrs of motor symptoms

DLB vs PDD

2/3 pts with DLB have parkinsonism

In DLB, < resting tremor, <asymmetry and >rigidity, postural and gait impairment

• In autopsy-proven cases, one of myoclonus, absence of rest tremor, no response to levodopa, or no perceived need to treat with levodopa, was10X more likely to represent dx of DLB than PDD

• Progressive supranuclear palsy– Supranuclear downgaze palsy, (difficulty

looking down )

– Upright posture ,broad-based and stiff gait postural instability /frequent falls

– Axial rigidity, nuchal dystonia ( neck in extension )

Neurodegenerative disorders with Parkinsonism

www.wemove.org

• Progressive supranuclear palsy

– Pseudobulbar emotionality/ emotional incontinence

– -Furrowed brow/stare

– Dementia

– - poor response to levodopa

Neurodegenerative disorders with Parkinsonism

www.wemove.org

• Corticobasal degeneration

– Unilateral akinesia and rigidity, coarse tremor ,unresponsive to levodopa

– Limb apraxia/ limb dystonia

– alien limb

– myoclonus

Neurodegenerative disorders with Parkinsonism (II)

www.wemove.org

Neurodegenerative disorders with Parkinsonism (III)

• Multiple system atrophy– Shy-Drager syndrome

• Autonomic insufficiency—orthostasis, impotence

– Striatonigral degeneration• Tremor less prominent

– Olivopontocerebellar atrophy• Cerebellar signs

www.wemove.org

Neurodegenerative Disorders with Parkinsonism (IV)

• Alzheimer’s disease

– Dementia is the primary clinical syndrome

– Rest tremor is rare

www.wemove.org

Hereditary disorders associated with parkinsonism:

– Wilson’s disease

– Huntington’s disease

– Dentatorubro-pallidoluysian atrophy (DRPLA)

– Machado-Joseph disease (SCA-3)

Differential Diagnosis of PD:

www.wemove.org

Differential Diagnosis of PD:

Secondary Parkinsonism• Drug-induced

• Toxin-induced

• Metabolic

• Structural lesions (vascular parkinsonism, etc.)

• Hydrocephalus

• Infectionswww.wemove.org

• Early onset of, or rapidly progressing, dementia

• Rapidly progressive course

• Supranuclear gaze palsy

• Upper motor neuron signs

• Cerebellar signs—dysmetria, ataxia

• Urinary incontinence

• Early symptomatic postural hypotension

Clues Suggesting Atypical Parkinsonism

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TREATMENT OFTREATMENT OFCOGNITIVE IMPAIRMENTCOGNITIVE IMPAIRMENTIN PARKINSON’S DISEASEIN PARKINSON’S DISEASE

•Cholinesterase inhibitor

•Avoid offending medications

•Symptomatic behavioral treatment

•Caregiver education

Altered Mental States NYD

• Confusion, sedation, dizziness, hallucinations, delusions

• Reduce or eliminate CNS-active drugs of lesser priority– anticholinergics – sedatives– amantadine – muscle relaxants– hypnotics – urinary spasmodics

• Reduce dosage of DA, COMT inhibitor, or LD

www.wemove.org

Treatment

• Order for elimination of PD meds

-Anticholinergics

- Selegiline

- Amantadine

- Dopamine agonists

- COMT inhibitors

- Levodopa

TREATMENT OF NEUROPSYCHIATRIC TREATMENT OF NEUROPSYCHIATRIC PROBLEMS IN PARKINSON’S DISEASEPROBLEMS IN PARKINSON’S DISEASE

•Reduce / discontinue medications

•Treat underlying medical illness

•Antidepressants

•Atypical neuroleptics

•Keep active / exercise

•Educate caregivers

•Psychological counseling

Where and When Do Geriatric Psychiatrists See PD Patients ?

• Often involved with complex cases - Associated behavioural disturbances - Other psychiatric comorbities - Other medical comorbities • Multiple settings - Impatient consultation-liaison - Impatient psychiatry - Nursing homes - Freeport Neurobehaviour Unit - Emergency room

References Menza M ,Marsh L

Psychiatric Issues in

Parkinson’s Disease Taylor&Francis 2006

Treatment of Psychiatric Co-morbidities in Patients with Parkinson’s Disease

McDonald, W.H.,Chair

Symposium AAGP March 2008

Slides; Houston Medical Center –

Parkinson’s Disease Research, Education, and Clinical Center

Slides; WE MOVE Parkinson’s

Disease Teaching Slide Set www.wemove.org