Transcript Parkinson's Disease: Epidemiology, Etiology, and Pathogenesis
PSYCHIATRIC ASPECTS of PARKINSON’S DISEASE
and Related Disorders
Michael J Kelly MD FRCPC Grand River Hospital Kitchener-Waterloo 7 May 2008
Learning Objectives
Recognize the psychiatric co-morbidities associated with Parkinson’s Disease and related disorders Better appreciate management of the 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
Maintain motion Treatment 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 NEUROPSYCHIATRIC SYMPTOMS SYMPTOM Anxiety Fatigue Irritability Hallucinations Self-withdrawal Euphoria Lassitude/weariness Sadness Witjas T et al. Neurology, 2002;59:408-413.
FREQUENCY % 66 56 52 49 44 42 42 38
RISK FACTORS FOR NON-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 cases www.wemove.org
DEPRESSION IN PARKINSON’S DISEASE
• Affects 40-50% of patients • Characterized by: Feeling of guilt Lack of self esteem Loss of initiative Helplessness, 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 •
Underdiagnosis:
- Bradykinesia, masked facies mask depression - Cognitive impairment - Bradyphrenia - Low voice - Ageism - Lack of attention to emtional problems - Apathy
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
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Depends on definition of psychosis, Parkinson’s disease (PD), congnitive impairment
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~5%-17% without significant dementia
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~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
Quetiapine Most common first-line agent 6.25-12.5 mg starting dose Escalate as needed/tolerated Adverse effects - Sedation - Orthostasis - Confusion - Increased parkinsonism, especially with dementia - Increased fluctuations
Clozapine Most effective agent for psychosis in PD, but use avoided because of need for blood monitoring Dose range: 6.25 mg od ≥ 200 mg/day Starting dose 6.25 mg qhs Escalate as needed/tolerated Adverse effects - Sedation - Orthostasis - Confusion - Worse parkinsonism - Agranulocytosis - 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 PD Pathological Gambling Hypersexuality Pathological Shopping Compulsive Eating Dopaminergic Medication abuse Punding
ICDs: General Treatment Strategoes Adjust antiparkinsonian treatment – Reduce dosage of dopaminergic medications – Change to a different dopamine agonist – Discontinue dopamine agonist Pharmacologic trials- anecdotal – Quetiapine and clozapine – Antiandrogens, valproate, lithium, atomoxetine, treatment of comorbid depression Psychosocial supports – Limit access to behaviours – Counseling, psychotherapy, CBT, Gamblers Anonymous
SLEEP DISTURBANCES IN PARKINSON’S DISEASE
• Insomnia • REM behavior disorder • Nightmares • Obstructive sleep apnea • Excessive daytime sleepiness
• • •
COGNITIVE IMPAIRMENT IN PARKINSON’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,
Neurodegenerative disorders with Parkinsonism •
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 ) www.wemove.org
Neurodegenerative disorders with Parkinsonism •
Progressive supranuclear palsy
– Pseudobulbar emotionality/ emotional incontinence – – Dementia – -Furrowed brow/stare - poor response to levodopa www.wemove.org
Neurodegenerative disorders with Parkinsonism (II) • Corticobasal degeneration – Unilateral akinesia and rigidity, coarse tremor ,unresponsive to levodopa – Limb apraxia/ limb dystonia – alien limb – myoclonus 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
Differential Diagnosis of PD:
Hereditary disorders associated with parkinsonism: – Wilson’s disease – Huntington’s disease – Dentatorubro-pallidoluysian atrophy (DRPLA) – Machado-Joseph disease (SCA-3) www.wemove.org
Differential Diagnosis of PD:
• • • • • • Secondary Parkinsonism Drug-induced Toxin-induced Metabolic Structural lesions (vascular parkinsonism, etc.) Hydrocephalus Infections www.wemove.org
Clues Suggesting Atypical Parkinsonism • • • • • • • 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 www.wemove.org
TREATMENT OF COGNITIVE IMPAIRMENT IN 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 PROBLEMS 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