PD: Key Treatment Considerations 2018 Management of Neurologic and Neurosurgical Disorders in Daily Practice Elise Anderson MD Medical Co-Director, PBSI Movement Disorders 11/27/2018 1
Outline Treatment of motor symptoms Nonmotor symptoms Comorbid disease Surgical: Deep Brain Stimulation Referrals and collaboration Patient case
PD: Principles of Treatment Inter-disciplinary approach Primary care Physical therapy Speech therapy Occupational therapy Psychiatry/psychology Social work Non-motor symptoms Caregiver support Medical & surgical therapies
PD: principles of treatment Treatment with medication is symptomatic: We start meds when symptoms start to affect quality of life Different for every patient: age, occupation, concerns about side effects, comorbid conditions all affect recommendations No disease modifying therapy exists (yet!) 11/27/2018 4
Medical therapy of motor PD symptoms Anticholinergics MAO-B inhibitors Dopamine agonists Carbidopa/Levodopa (Sinemet, Rytary, Duopa) COMT inhibitors
Anticholinergics Trihexyphenidyl, cogentin, others Counters cholinergic overactivity in PD Good treatment for tremor Significant confusion and urinary retention Avoid in patients with cognitive impairment or > 65 years old
MAO-B inhibitors Selegiline (Eldepryl) Rasagiline (Azilect) Safinamide (Xadago) Interactions: Tyramine-containing foods (some cheeses, processed meats) producing hypertensive crisis Serotonergic antidepressants and some pain meds Disease modification: mixed results ADAGIO study: rasagiline 1 mg daily, delayed start study design, supported protective effect of rasagiline, but not rasagiline 2 mg daily Olanow, CW, et al. NEJM. 2009;361:1268-78.
Dopamine agonists Dopamine agonists Pramipexole, ropinirole - TID and qday dosing Rotigotine 24hr patch Apomorphine injectable rescue med, continuous pump in Europe Less potent than levodopa Side effects: GI upset, fatigue, impulse control disorder (ICD) ICD is seen with sinemet and in agonist therapy for RLS too Best for milder disease, levodopa sparing strategy?
Sinemet: carbidopa-levodopa Most potent and effective medication for PD BUT, dyskinesia and motor fluctuations develop as disease progresses Sinemet: combination pill Levodopa converted to dopamine by dopadecarboxylase in the brain Carbidopa inhibits dopadecarboxylase outside the brain, does not cross blood brain barrier
Formulations of levodopa Sinemet: immediate release IR and extended release CR formulations Rytary: newer extended release formulation Duopa: intestinal gel formulation of carbidopa/levodopa Continuously delivered via J-PEG, pt wears cartridge of med in a fanny pack
Levodopa side effects, immediate Nausea: often improves with small carbohydrate snack. Avoid taking with meals due to competition with protein for absorption Best taken 30 min before or 60 min after meals Fatigue: can improve with snack Some patients need a VERY slow titration, eg starting a quarter tab TID 11/27/2018 11
Levodopa: dyskinesia
Levodopa side effects: down the road Dyskinesia: involuntary wiggly movements Dopamine depletion & dopaminergic therapy in gene expression producing involuntary movement Consider decrease levodopa dose and shorten dosing interval Rx: amantadine (Gocovri?), DBS Motor fluctuations Effects wear off, slowness and tremor progress, after a while increasing meds doesn t help as much. Options: Rytary more on time with less dyskinesia Entacapone increases levodopa half life
Levodopa side effects, con t Psychosis: caused by both ipd and sinemet (and other PD meds ) Rare early in disease but cumulative incidence 50% Predictor of early long-term care placement Orthostatic hypotension: due to both ipd and levodopa 11/27/2018 14
Which therapy first? Minimally affected: PT and exercise! Tremor only: consider trihexyphenidil Younger patients (<60) Mildly affected: MAO-B inhibitor, dopamine agonist Typical ipd (mid 60 s and up) Carbidopa-levodopa (sinemet): OK to start 1 tab TID when you refer we can assess response at first visit! Agonist? We may be shifting towards using agonists as adjunctive therapy rather than first line, except in young onset patients
Nonmotor symptoms of PD Anxiety/depression: often predates motor symptoms, can be first symptom of PD Anxiety can be a wearing off symptom of levodopa Neurocognitive changes: early in PD - executive dysfunction, visuospatial impairment Sleep disruption Fatigue 11/27/2018 16
Nonmotor symptoms, con t Dysautonomia: constipation, urinary issues, orthostatic hypotension Stop antihypertensives, increase fluids and salt, elevate head of bed, abdominal binders/compression stockings Rx: fludrocortisone, midodrine, droxidopa Psychosis: mild hallucinations are common, can progress to paranoia, disruptive or frightening hallucinations Peel back other meds, decrease sinemet (esp late in the day) Consider cholinesterase inhibitor, seroquel, pimavanserin 11/27/2018 17
Comorbid disease PD meds have minimal interactions with other meds Except MAO-B inhibitors, eg interaction with dextromethorphan in OTC cold meds and some pain meds (like codeine, demerol) Medical illness will exacerbate PD symptoms But does not accelerate disease Avoid adjusting PD meds during acute illness 11/27/2018 18
Partnering with Primary Care Depression: I ll often start or adjust antidepressants, but appreciate help from PCP for more complicated medication adjustments Medical issues in PD: Severe constipation: I call you when it s time for lactulose! Acute status changes: I tend to order screening labs but call you if they are abnormal Dysautonomia: especially if medically complicated, eg CHF 11/27/2018 19
Surgical options Deep Brain Stimulation (DBS) Subthalamic nucleus: most directly mimics levodopa effect Globus Pallidus interna: antidyskinetic effect Also for generalized dystonia, FDA humanitarian approval Thalamus (essential tremor) Stem cell, gene therapy: not there yet!
Deep Brain Stimulation Advantages Flexible: programmable to optimize therapy Acts like a low level of dopamine in system all the time Medication reduction Reduces OFF time/motor fluctuations Decreased dyskinesia - anti-dyskinetic effect with GPi Disadvantages Surgical procedure - Risks: seizure, bleed, infection Cognitive impairment: neuropsych eval required Can make imbalance & dysphagia worse: PT, ST eval
When to refer for surgery? Med side effects become disabling the end of the honeymoon" Motor fluctuations, unpredictable OFF s Dyskinesia Pt has a clear response to levodopa: best predictor of DBS benefit No/minimal cognitive impairment Patient selection (and education) is key! Red flags: postural instability and freezing, dysarthria/dysphagia, cognitive impairment, depression
Case: Pt WD CC: ipd, syncope, delirium 73 year old man with ipd, dx d in 2009 after 4 years of progressive gait changes and tremor. S/P b/l STN DBS in 2017, with marked improvement in hallucinations and cognitive function due to subsequent med reduction Now with episodes of syncope, also confusion, delusions, hallucinations 11/27/2018 23
Pt WD, con t 3/2018: pt presents to ER after syncopal event and fall, striking his head Pt is paranoid and confused in ER BP is 70/30 CTH and exam are stable Plan: PCP: Holter and BP monitoring, consider cholinesterase inhibitor (pt with history of heart block) Me: Add seroquel at HS 11/27/2018 24
Pt WD con t 2 weeks later: Holter and BP monitoring reviewed: OK to start donepezil and midodrine Pt improved on HS seroquel 3 months later: Pt cognitive function much better, back to playing bass OK to D/C seroquel 11/27/2018 25
Thank you! Questions? 11/27/2018 26