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Management of Late-Stage Parkinson’s Disease Part 5 of 7 www.wemove.org Parkinson’s Disease Slide Library Version 2.0 - All Contents Copyright © WE MOVE 2001 Late Complications • Motor – response fluctuations, dyskinesias, dystonia, freezing, falls • Behavioral/neuropsychological – depression, sleep disorders, psychosis • Autonomic – orthostatic hypotension; hyperhidrosis, constipation, impotence, urinary incontinence or retention www.wemove.org Stages in Decline of Response to LD • I: Patient not aware of effect of individual dose • II: Mid-afternoon loss of benefit • III: Loss of sleep benefit; early-morning akinesia, possible foot dystonia • IV: Regular “wearing off” every 4 hours at first, shortens with time • V: Frequent wearing off, abrupt on-off, unpredictable dose response www.wemove.org LD Response Fluctuations • Peripheral causes: – delayed gastric emptying – dietary protein – short plasma half-life • Central causes: – pulsatile delivery to striatal receptors – impaired storage capacity – alteration of DA receptors www.wemove.org Response Fluctuations: Treatment • • • • Increase LD dose Increase DCI dose Add dopamine agonist Add COMT inhibitor – reduce LD – liver function monitoring • Apomorphine rescue www.wemove.org Peak Dose Dyskinesia or Dystonia • • • • Chorea more common than dystonia May be worse on more affected side May not be as disabling as akinesia/rigidity Dose adjustments, add-ons: – reduce LD dose, increase dose frequency – convert to LD-CR – reduce LD, add DA, COMT inhibitor, or MAOB inhibitor www.wemove.org Off-period Dystonia • Appears when LD level is low, especially early AM • w/ or w/o parkinsonism • Dose adjustments, add-ons: – more frequent LD dosing to avoid low plasma levels – add DA, COMT inhibitor, MAO-B inhibitor www.wemove.org Wearing Off • Regular and predictable decline in response 2-4 hours after LD dose • Most common motor fluctuation • Dose adjustments, add-ons: – change to LD-CR, or increase LD frequency – reduce LD, add DA or COMT inhibitor www.wemove.org On-off Response • Sudden and unpredictable off periods unrelated to dosing schedule • One of the hardest features to manage • Dose adjustments, add-ons: – reduce LD, add DA www.wemove.org Other Motor Complications • Diphasic dyskinesia – dyskinesia at beginning and end of dose – Dose adjustments, add-ons: add DA • Drug failure – late afternoon, probably related to poor gastric emptying or absorption – liquid preparations; increase gastric motility; decrease dietary protein – apomorphine rescue www.wemove.org Freezing and Falls • Freezing – motoric block; at initiation of gait, turning, narrow spaces – use auditory, visual, proprioceptive cues • Falls – physical therapy evaluation – cane, scooter, wheelchair may be necessary www.wemove.org Cognitive Assessment • Memory difficulties: 11-29% of PD patients – – – – Benign forgetfulness Delirium Alzheimer’s disease Other dementias • Evaluation – – – – Brain imaging Lumbar puncture EEG Blood work for thyroid profile, vitamin B12, serology, chemistry panel www.wemove.org Psychosis • Features – Vivid dreams/nightmares, disorientation, hallucinations, delusional thought • Simplify medical regimen – Stop unnecessary non-PD meds – Stop: anticholinergic drugs, amantadine, selegiline, dopamine agonists, COMT inhibitors • Change from CR to standard carbidopa/levodopa • Try atypical antipsychotic agents • Try low-potency traditional antipsychotic agents www.wemove.org Anti-psychotic Agents • Molindone – low-potency neuroleptic; may aggravate PD symptoms, but can sometimes use 5-10 mg at HS • Risperidone – D3 antagonist; D1/D2 agonist; aggravates PD at doses > 3 mg/d. • Olanzapine – D4 antagonist. D1/D2 inhibition > 10 mg/d • Quetiapine – 5-HT1-2 antagonist. Dosage 25 - 500 mg/d • Clozapine – D4 antagonist; no confirmed aggravation of PD or causation of TD – Fatal agranulocytosis in 9 patients; weekly CBC www.wemove.org Depression • • • • Reported in 30-90% of PD patients Difficult to discern from vegetative symptoms Requires inquiry into depression symptoms Usually responds quickly to medications – Tricyclic agents – Selective serotonin re-uptake inhibitors • If ECT needed, will transiently improve PD symptoms www.wemove.org Anxiety/Restlessness • Primary anxiety disorder: treat with benzodiazepines – Associated with “off-periods” or low-levodopa levels: adjust levodopa dosing • Restless Leg Syndrome: benzodiazepines, narcotics, levodopa, dopamine agonists www.wemove.org Sleep Disorders • Insomnia – careful history – difficulty with sleep initiation: tricyclic agents, benzodiazepines, diphenhydramine, chloral hydrate – treat depression – REM-behavioral disorder: clonazepam • Excessive daytime sleepiness – – – – Correct poor sleep at night Discontinue anticholinergics, amantadine Reduce dopamine agonist, levodopa dosages if possible selegeline; caffeine; methylphenidate 5-20 mgs/d www.wemove.org Orthostatic Hypotension • Light-headedness, dizziness, fatigue, shoulder or neck pain, blood pressure drops when standing • Taper anti-hypertensive agents • Taper non-PD drugs • Increase salt intake • Compression stockings • Fludrocortisone (0.1-0.4 mg/d) • Midodrine (2.5 - 20 mg/d) www.wemove.org Urinary Incontinence/Frequency • Rule out urinary tract infection • Bladder evaluation for – detrusor hyperactivity • oxybutinin 5 -30 mg/d; propanthaline 7.5 - 15 mg/d – detrusor hypoactivity • phenoxybenzamine; prazosin • Urinary frequency – avoid fluid pooling in feet – DDAVP inhaler; tolterodine tartrate 2mg hs to 2mg tid www.wemove.org Sexual Dysfunction • Medical screening – depression, anxiety, iatrogenic causes • Endocrinologic evaluation – prolactin, testosterone, lutenizing hormone, thyroid screen • Urologic evaluation – yohimbine, sildenafil www.wemove.org Nausea • Levodopa-related: take with meals, add carbidopa, add domperidone • Other anti-PD medications: same. – If no improvement: withdraw newest agent, reinitiate at minimal doses, slowly increase www.wemove.org Excessive Sweating • Usually levodopa related, and may be seen at peak or trough dose drug levels – – – – reduce levodopa add dopamine agonist or COMT inhibitor add carbidopa add Beta-blocker www.wemove.org Faculty for the WE MOVE Parkinson’s Disease Teaching Slide Set Mark Stacy, MD Barrow Neurological Institute Phoenix, Arizona, USA Richard B. Dewey, Jr., MD University of Texas Southwestern Medical Center Dallas, Texas, USA Charles H. Adler, MD, PhD Mayo Clinic Scottsdale Scottsdale, Arizona, USA William G. Ondo, MD Lisa M. Shulman, MD Baylor College of Medicine Health Policy Fellow Houston, Texas, USA U.S. House of Representatives Washington, DC, USA Rajesh Pahwa, MD University of Kansas Celia Stewart, PhD Medical Center Mount Sinai Medical Kansas City, Kansas, USA Center New York, New York, USA Kathleen Albany, PT, MPH WE MOVE New York, New York, USA Ali H. Rajput, MD Royal University Hospital Saskatoon, Saskatchewan, Canada Reviewed by the Education Committee of the Movement Disorder Society www.wemove.org