psychiatric aspects of parkinson’s disease and related disorders michael j kelly md frcpc grand...
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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
www.wemove.org
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