Management of Parkinson s Disease in Primary Care

Transcription

1 Management of Parkinson s Disease in Primary Care Dr June Tan National University Hospital System (NUHS) Division of Neurology Senior Consultant

2 Topics: Diagnosing PD Choice of medication in the de novo pt Treatment of motor fluctuation Non-motor complications

3 Approach to diagnosis of PD: Confirm the presence of parkinsonism Detect atypical features that suggest an alternative diagnosis to PD

4 Approach to diagnosis of PD: Confirm the presence of parkinsonism Detect atypical features that suggest an alternative diagnosis to PD

5 Parkinsonism Parkinsonism refers to the presence of rest tremors leadpipe rigidity bradykinesia These are the 3 cardinal features of PD

6 The motor features in early PD are often asymmetric at disease-onset respond well to levodopa Note: these features are not specific to PD if considered separately.

7 Approach to diagnosis of PD: Confirm the presence of parkinsonism Detect atypical features that suggest an alternative diagnosis to PD

8 Exclusion of alternative diagnoses Conditions which may mimic PD include: atypical parkinsonian syndromes (MSA, PSP, DLB, CBD, AD) drug-or toxin-induced parkinsonism cerebrovascular disease encephalitis hydrocephalus recurrent head trauma

9 Exclusion of alternative diagnoses Young-onset parkinsonism may be due to Huntington s disease Westphal variant Wilson s disease Dopa-responsive dystonia The tremors in PD may be misdiagnosed as Essential tremors Enhanced physiological tremors Dystonic tremors

10 Red Flags in PD Early frequent falls Early dementia Early hallucinations Early bulbar symptoms Early impaired EOM Early dysautonomia Early means within 1 year of onset Rapid deterioration Symmetrical motor signs Poor/no response to L-dopa Pyramidal signs Cerebellar dysfxn Apraxia, cortical signs

11 Investigations No gold standard investigation to diagnose PD Instead, clinical criteria are used to increase diagnostic accuracy In patients with typical features of PD in the correct age group, no further investigations are required for diagnosis. However, patients with young-onset parkinsonism, and patients with unusual or atypical features require further investigations to exclude alternative diagnoses.

12 Choice of medication in de novo patients

13 Which one is best for my patient?

14 In PD, decision on when to treat and what to use is highly individualized. Why? Choice of therapy depends on: Regional availability of drug Patient factors: e.g functional age, pre-morbid status, stage of disease, co-morbidities, expectations, financial means, etc Physician s familiarity with PD meds Understanding of disease progression & aim of treatment

15 Aim of treatment Cure? No evidence Slow disease progression? Putative evidence for ropinirole, pramipexole and rasagiline Symptomatic treatment? Yes, motor symptoms respond well in early stages. Improves quality of life

16 Aim of treatment Cure? No evidence Slow disease progression? Putative evidence for ropinirole, pramipexole and rasagiline Symptomatic treatment? Yes, motor symptoms respond well in early stages. Improves quality of life

17 MOTOR FLUCTUATIONS and how they influence our choice of medication

18 Levodopa s history, potency and eventual fall from grace Levodopa-induced motor fluctuations in PD Inevitable, occurs at rate of 10% per year of L-dopa treatment Causes significant deterioration in QOL L-dopa induced dyskinesia is the commonest cause of choreoathetosis seen in clinical practice

19 Early PD, no motor fluctuation Dyskinesia threshold time L-dopa

20 Dyskinesia threshold Early morning foot dystonia Wearing OFF nocturnal akinesia time

21 More robust and rapid but shorter ON, peak dose dyskinesia, deep OFF Dyskinesia threshold time

22 Dose failure Sudden OFF Dyskinesia threshold time

23 Peak-dose dyskinesia Dyskinesia threshold Biphasic dyskinesia time

24 Problems caused by dyskinesia Hypercatabolic state Axial imbalance Impaired limb function Impaired ability to fall asleep Social embarassment

25 Try and delay the onset of motor fluctuations for as long as possible

26 Natural course without medication Diagnosis preclinical motor symptoms + dementia + non-motor symptoms onset

27 Natural course without medication Diagnosis preclinical motor symptoms + dementia + non-motor symptoms onset

28 Natural course without medication Diagnosis preclinical motor symptoms + dementia + non-motor symptoms onset

29 Pulsatile dopaminergic stimulation Continuous dopaminergic stimulation (CDS) delays onset of motor fluctuation

30 Commonly available drugs for early PD L-dopa (Madopar, Sinemet) Dopamine agonists (eg Ropinirole, Pramipexole, Piribedil, Bromocriptine) MAOBI (eg Selegiline) Anticholinergics (eg Benzhexol) NMDA antagonists (eg Amantadine)

31 Dopamine agonists (eg Ropinirole, Pramipexole, Piribedil, Bromocriptine) Longer T1/2 Directly stimulates dopamine receptors, bypasses neuronal storage issues Gives a more stable drug level Delays onset of motor complications Ropinirole & pramipexole have putative neuroprotective effects

32 Dopamine agonists Limitations: Less potent than L-dopa General side effects: nausea, sleepiness, ankle edema, giddiness. Neuropsychiatirc manifestations: Confusion and psychosis - esp in elderly Impulse Control Disorders Punding Ergot-derived DAs (e.g. bromocriptine, carbegoline, lisuride, pergolide) may cause fibrosis Non-ergot DAs are relatively costly.

33 MAOBI (eg Selegiline, Rasagiline) Inhibits breakdown of L-dopa, so more can be used by the brain Used as monotherapy in mild cases or add-on in motor fluctuations Selegiline Mild motor benefit 5mg twice a day, last dose before 5pm Limitations: Drug interactions with TCAs, SSRIs, dextromethorphan serotonin reaction Similar to cheese reaction with tyramine-rich food (Bovril, aged cheese, alcohol) MAOBIs may worsen psychosis

34 Amantadine Anti-viral agent NMDA antagonist Use as single agent in mild cases or add-on to L-dopa Mild motor benefit Anti-dyskinetic properties but benefit often lasts < 1 year Limitations: Side effects psychiatric, skin rashes Cost issues Caution in renal disease

35 Anticholinergics (e.g benzhexol) Use as monotherapy in mild disease or add-on to L-dopa Mild motor benefit Not well tolerated by elderly pts Hallucinations, psychosis Dry mouth and eyes Constipation Contraindicated in patients with urinary retention, glaucoma

36 Pt s functional age Pt s expectations Pt s existing medical conditions Need to treat? Yes Not yet What to use? Regular review Stage of PD Pt s financial means Availability of drugs

37 General principles: Engage the patient in deciding which drugs to use and when to start Start low, go slow Single agent Monitor for side-effects Monitor for disease progression and need for dose adjustment

38 General principles: 2 ends of the spectrum: Mild motor symptoms in elderly frail patient with multiple medical conditions or dementia not to treat or start cautiously with L-dopa

39 General principles: 2 ends of the spectrum: Good physical and mental status (regardless of age) - delay use of L-dopa as long as possible start with DA or MAOBI, add on L-dopa only when needed - young patients can better tolerate benzhexol and amantadine

40 Management of motor fluctuations

41 Motor response WEARING OFF Time L-dopa/DDI WEARING OFF add DA or long-acting MAOBI L-dopa/DDI + DA or long-acting MAOBI

42 Motor response WEARING OFF add COMTI Time L-dopa/DDI + COMTI WEARING OFF last resort: use frequent L-dopa Frequent doses of L-dopa/DDI erratic response, may be better than nothing

43 Motor response Night-time OFF, early morning dystonia Time L-dopa/DDI Motor response L-dopa/DDI L-dopa/DDI + L-dopa HBS or COMTI Time Or L-dopa/DDI doses through the night - erratic

44 Motor response REFRACTORY OFF Time L-dopa/DDI s/c apomorphine or liquid L-dopa

45 Motor response Absorption failure Time L-dopa/DDI lunch dinner Motor response Adjust meal times, smaller protein portions Time lunch dinner

46 Motor response Peak-dose dyskinesia Time Motor response L-dopa/DDI Time L-dopa dose, + DA or COMTI or MAOBI

47 Motor response Biphasic dyskinesia Sleep Time L-dopa/DDI Motor response Sleep Time s/c apomorphine or liquid L-dopa L-dopa/DDI L-dopa/DDI L-dopa/DDI

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49 NON-MOTOR SYMPTOMS

50 Non-motor manifestations of PD Autonomic, neuropsychiatric, olfactory and sensory Common and prominent in later stages of PD Relatively resistant to, and may be worsened by PD meds Cause significant disability Often neglected in PD management. Remember to screen your pts for non-motor symptoms

51 Natural course without medication Diagnosis preclinical motor symptoms + dementia + non-motor symptoms onset Postural hypotension Dysphonia Dysphagia Constipation Urinary incontinence Pain syndromes Depression Hallucination Gait difficulties: Axial instability Freezing Start hesitancy Listing Shuffling Propulsion

52 Non-motor symptoms Some worsened by anti-pd meds May need to decrease or stop these meds at the expense of motor benefit Symptomatic meds can alleviate some non-motor problems But does not cure it and may add to side effects in elderly Physio, occupational, speech therapists play very important role at this stage Physical therapy is an effective and often safer choice compared to adding on more and more meds Decreasing anti-pd meds dose