PSYCHIATRIC ASPECTS of PARKINSON’S DISEASE and Related Disorders

1. PSYCHIATRIC ASPECTS of PARKINSON’S DISEASEand Related Disorders Michael J Kelly MD FRCPC Grand River Hospital Kitchener-Waterloo 7 May 2008

2. Learning Objectives • Recognize the psychiatric co-morbidities associated with Parkinson’s Disease and related disorders • Better appreciate management of the common neuropsychiatric complications

3. 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

4. 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

5. James Parkinson 1817 • “ a more melancholy object I never beheld”

6. 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

7. Treatment Maintain motion Control emotion “Motion-Emotion Conundrum”

8. 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.

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

10. FREQUENCY OF NEUROPSYCHIATRIC SYMPTOMS Witjas T et al. Neurology, 2002;59:408-413.

11. 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

12. 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

13. 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

14. Key Features of Depression in PD • Reported dysphoria/sadness • Apparent sadness • Anhedonia • Exaggerated pessimism • Suicidal ideation • Irritability • Comorbid anxiety

15. 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 Diagnostic Difficulties

16. Potential Mechanisms • Psychosocial stress in general • Genes • Comorbidity • Structural and functional brain changes • Antiparkinson agents • Latent psychiatric disease • Psychological reaction to diagnosis and impairment

17. 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?

18. 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

19. 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

20. 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

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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. Impulse Control Disorders (ICDs) in PD • Pathological Gambling • Hypersexuality • Pathological Shopping • Compulsive Eating • Dopaminergic Medication abuse • Punding

31. 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

32. SLEEP DISTURBANCES IN PARKINSON’S DISEASE • Insomnia • REM behavior disorder • Nightmares • Obstructive sleep apnea • Excessive daytime sleepiness

33. COGNITIVE IMPAIRMENT INPARKINSON’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

34. 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 PD with Dementia

35. Neurodegenerative Disorders with Parkinsonism (I) • Diffuse Lewy body disease • Early onset of dementia • Delusions and hallucinations • Agitation www.wemove.org

36. 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

37. 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

38. 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

39. 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

40. Neurodegenerative disorders with Parkinsonism • Progressive supranuclear palsy • Pseudobulbar emotionality/ emotional incontinence • -Furrowed brow/stare • Dementia • - poor response to levodopa www.wemove.org

41. 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

42. 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

43. Neurodegenerative Disorders with Parkinsonism (IV) • Alzheimer’s disease • Dementia is the primary clinical syndrome • Rest tremor is rare www.wemove.org

44. 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

45. Differential Diagnosis of PD: Secondary Parkinsonism • Drug-induced • Toxin-induced • Metabolic • Structural lesions (vascular parkinsonism, etc.) • Hydrocephalus • Infections www.wemove.org

46. 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

47. TREATMENT OF COGNITIVE IMPAIRMENT IN PARKINSON’S DISEASE • Cholinesterase inhibitor • Avoid offending medications • Symptomatic behavioral treatment • Caregiver education

48. 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

49. Treatment • Order for elimination of PD meds -Anticholinergics - Selegiline - Amantadine - Dopamine agonists - COMT inhibitors - Levodopa

50. 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