Download PARKINSON`S DISEASE (PD): Drug Comparison Chart 1,2,3,4,5,6

 PARKINSON'S DISEASE (PD): Drug Comparison Chart 1,2,3,4,5,6 GENERIC/TRADE THERAPEUTIC USE / COMMENTS Brent Jensen BSP © www.RxFiles.ca Jul 13 CONTRAINDICATIONS CI / ADVERSE EVENTS AE / INITIAL, USUAL & MAXIMUM DOSE DRUG INTERACTIONS DI / MONITORING M $/MON (Strength & formulations) DOPAMINE PRECURSOR: levodopa (l‐dopa) – most potent medication for PD. Effective cornerstone of therapy. DOPAMINE DECARBOXYLATION INHIBITORS: benserazide & carbidopa ‐ È peripheral conversion of l‐dopa to dopamine Æ È l‐dopa dose & Ècardiac arrhythmias, N/V (≥75mg carbidopa blocks enzyme; 7 may need ≤200mg to È nausea). $25 PROLOPA: Initial: 50/12.5mg BID, ↑q3‐7 d Levodopa/benserazide 9 Idiopathic, postencephalitic & symptomatic PD esp. if pt CI: MAOI use, caution if psychosis history, glaucoma, Usual dose: 100/25mg TID‐QID cc $52‐63 sympathomimetic amines & may activate melanoma. PROLOPA contains phenylalanine P L
rigid, bradykinesia or elderly. $83 AE: Common: GI: nausea, vomiting, anorexia; CNS: headache, 200/50mg TID cc 50/12.5, 100/25, 200/50mg cap Restless leg symptoms (e.g. 100/25mg HS) see RxFiles page 78. $261 Maximum dose: ≥2g/day st
confusion, dizziness, hallucination, mood change, 8
Levodopa/carbidopa Comments: 1 line for PD (or start with a DA) SINEMET: Initial: 50/12.5mg BID,↑q3‐7 days $25 nightmare, insomnia, depression; rash, alopecia rare, ‐ Levodopa has superior motor benefit but an↑risk of SINEMET/SINEMET CR, g Usual dose: discolored urine, dark saliva/sweat & Çlibido. dyskinesia.1 American 2002 less likely if resting tremor initially IR: 100/25mg TID‐QID cc to 250/25mg TID cc $34‐46 100/10, 100/25, 250/25mg IR tab Dose unresponsiveness & freezing, fluctuations ‐ Wearing off, on‐off phenomena, sudden offs & freezing CR: 100/25mg TID cc to 200/50mg BID‐TID cc $58‐140 100/25, 200/50mg CR tab (wearing off, on‐off), dyskinesia (chorea, peak dose, ς
Maximum dose: ≥2g/day $454 (g IR & CR tabs , except 100/25mg) & dyskinesia including painful dystonia affect ~ 40% of diphasic & dystonia off period; hand/foot in AM). 9
DUODOPA χ ⊗ Ç
dose 20‐30% when switching to CR for equivalent dose. pts within 5yr of starting levodopa.14 Serious: dyskinesia, ÈBP see below
, psychosis, arrhythmias, P L ‐ No evidence that CR levodopa better than regular 20mg/5mg/mL gel for STAVELO: Initial Dose: current l‐dopa dose sudden sleep, blood dyscrasia, neuroleptic malignant intraduodenal infusion Usual Dose: 50mg – 150mg TID $168 release, but may help to give CR at HS if early morning syndrome (NMS) esp. after abrupt tx d/c, malignant melanoma, Oral liquid form manufactured 15 (Koller)
Max Dose: 8 tabs/d (all strengths) $436 10,11
OFF episodes occurring.
anemia & È impulse control
14%, gambling, sex, spending. by some pharmacies.
‐ Dosing frequency is 3‐6x/day for IR. ?? Ç prostate cancer & MI with STALEVO.FDA (PARCOPA: rapid dissolving form of ‐ On‐off phenomenon: reduced by giving smaller, more ‐ An adequate trial is often ~3months 12
frequent levodopa doses or adding a DA. Correct ÈBP AE by: Ç water & salt intake if no history of HF
, levo/carbidopa avail in USA only ) of 200/50mg QID, but most patients midodrine 2.5 – 5 ‐ 10mg BID‐TID, domperidone, fludrocortisone ‐ Can be given up to 4 hours before surgery. Carbidopa/levodopa/ respond to lower dosages. NEJM'04, 16
13
0.05‐0.4mg/day & adjust antihypertensive & TCA doses. ‐ May slow progression or È
severity of symptoms.
Administration: entacapone STALEVO Domperidone 5‐10‐20mg TID ac to È nausea / hypotension ‐ Chew tablets & take with a carbonated 50 = 12.5/50/200mg tab P L ‐ Avoid abrupt withdrawal Æ worsen PD/cause NMS. DI: È effect of l‐dopa: antipsychotics, iron
È absorption
, 75 = 18.75/75/200mg tab drink to Ç absorption
even useful for IR tab
Pharmacokinetics: isoniazid, metoclopramide & pyridoxine only if levodopa 100 = 25/100/200mg tab esp. good for severe early morning sx. ‐ IR tab/cap: peak level at ~30minutes & ~4hr duration 17
alone; no effect if benserazide or carbidopa used. 125 = 31.25/125/200mg tab ‐ Protein rich foods may È absorption. ‐ CR tab: peak level at ~2 hr & ~5 hr duration – i.e. slower 150 = 37.5/150/200mg tab Çtoxicity: MAOI's non‐selective, antihypertensives, ‐ Take cc if nausea; ac for Ç absorption 2
onset, ~25% longer duration of action vs IR. (do not cut the tablets in half) ?caffeineÇl‐dopa absorption. of regular formulation. DOPAMINE AGONIST (DA): 18,19 active at various dopamine receptors (e.g. D1,2,3 or 4 subtypes). No disease modifying effects PDRG‐UK 14YR & also not seen with pramipexole0.5mg tid PROUD Pramipexole20,21,22,23,24,25 9 Idiopathic PD, may ↓off time ~15% (off‐label: cabergoline) CI: protease inhibitors, sibutramine with ergot agents; caution MIRAPEX: Initial Dose: 0.125mg TIDcc Çq7d $25 P L 9 Restless leg syndrome: pramipexole, ropinirole USA see pg 78. if psychosis & if uncontrolled hypertension. Usual Dose: 0.5‐1.5mg TID cc MIRAPEX, g $99‐74 0.125χ ⊗,0.25ς,0.5ς,1ς,1.5ς mg tab 9 Bromocriptine: acromegaly, galactorrhea +/‐ amenorrhea, AE: Common: GI: nausea domperidone may È nausea, vomiting, Maximum Dose: 1.5mg TID cc $74 constipation, anorexia; CNS: headache, confusion, dizziness, REQUIP: Initial Dose: 0.25mg TID cc Çq7d non‐ergot derivative to D2,3,4 hypogonadism, prolactin‐secreting adenoma.Off‐label: NMS.
$17 depression, dyskinesia, hallucinations; ÈBP, alopecia rare & Ropinirole 26,27,28,29 Usual Dose: 1‐5mg TID cc $46‐116 Comments: USA
ankle edema. REQUIP, g (Requip‐XL ) P L
Maximum Dose: 8mg TID cc $175 ‐ Non‐ergot derivatives pramipexole, ropinirole, (rotigotineUSA) are Serious: seizures, stroke, MI, punding, sudden onset of sleep 0.25,1,2,5mg tab PARLODEL: Initial: 1.25‐2.5mg BID cc Çq1‐2wk $39‐72 43,44,45
46,47
1st line for PD (or start with levodopa). Ergot derivatives episodes,
gambling,
Ç libido & spending, ?HF risk. non‐ergot derivative D2,3,4 $150‐290 Usual Dose: 5‐10mg TID cc bromocriptine, cabergoline & pergolide are not recommended as Ergot derivatives: pulmonary & retroperitoneal fibrosis, digital Bromocriptine 30,31,32,33,34 st
$290 Maximum Dose: 10mg TID cc 1 line due to concerns with cardiac valve disease see AE. spasms, limb/skin pain & Raynaud's like phenomena. Cardiac PARLODEL, g 48,49,50 $185 valve fibrosis 0.005%,
cabergoline:
? an 5HT2B effect, greater DOSTINEX: Initial Dose: 0.25mg OD ↑q2wk ‐ DA may have less motor complications than l‐dopa, but ς P L
2.5 mg tab; 5mg cap 51
$660‐ Usual Dose: 1‐3mg daily at 3mg/d & at >6month tx.
Ergot M: baseline/annual SCr, ESR, & Ç hallucinations, nausea, dizziness, somnolence & ergot derivative to D1,2 1920 1,42 American’02
Maximum Dose: 5mg daily chest x‐ray. Consider a baseline echo. 35,36,37
edema.
Not useful for freezing. Cabergoline $3185 DI: È effect DA therapy: antipsychotics, metoclopramide, P L ‐ Initiate at low dose & Ç gradually over 4‐6weeks. DOSTINEX, g $12 nitroglycerin È benefit of NTG
& omeprazole
for ropinirole
PERMAX: Initial Dose: 0.05mg daily ↑q7d ‐ At low doses DA have less benefit but still ↑AE. 0.5ς mg tab { hyperprolactinemia}
Ç DA toxicity: Pramipexole: amantadine, cimetidine, $75‐239 Usual Dose: 0.25‐1mg TID ‐ Can often È levodopa & DA dose when combined. ergot derivative to D2 diltiazem, quinidine, quinine, ranitidine, triamterene, verapamil $345 Maximum Dose: 1.5mg TID 2,42
38,39,40,41
‐ Possible preference in young (<50yrs) PD patients. Pergolide ‐ Ropinirole: ciprofloxacin, clari‐/erythromycin, fluvoxamine PERMAX, g d/c by company ’07 ‐ Can be given up to 4hrs before surgery. ‐ Itraconazole, propranolol & protease inhibitors especially with ‐ Taper dose if d/c medication, to prevent withdrawal sx. bromocriptine, cabergoline & pergolide, sibutramine. 0.05ς,0.25ς,1ς mg tabs P L ‐ Pramipexole: may benefit if depressed. ‐ Serotonin meds like SSRIs/MAOI ↑ risk of serotonin syndrome ergot derivative to D1,2 Rotigotine NEUPRO⊗ a non‐ergot DA D1,2,3 1,2,3,4,6,8mg daily patch aluminum (recalled→crystals but now returned). May Èearly sx & Çoff time in advanced dx. AE: N/V,ÇHR/BP/weight, skin rxn, dizzy, insomnia, nail dyschromia,edema. ANTICHOLINERGICS (AC): block acetylcholine in the striatum. Best to taper & discontinue over ~1 week when stopping! COGENTIN: Initial Dose: 0.5‐1mg HS Çq5d $8 Benztropine COGENTIN, g 9PD tremor (unknown if better for tremor vs other sx)52, Cochrane'03 CI: narrow angle glaucoma, ileus, BPH, myasthenia gravis, ς
Usual Dose: 1‐2mg BID $9‐11 obstructive uropathy. 2 mg tab; 2mg/2mL inj P L
53
Comments: Maximum Dose: 2mg TID $13 AE: Common: CNS: confusion,
drowsiness, headache, slow 3
Ethopropazine ‐ Useful for foot dystonia, ↓drooling & drug induced EPS. $11 P L
memory; AC: dry mouth, blurred vision, urinary retention, PARSITAN: Initial Dose: 25mg daily ς PARSITAN 50 mg tab $21‐36 constipation etc.; rash, Ç HR & È sweating (over heating). Usual Dose: 50‐100mg BID ‐ As monotherapy or adjunct therapy more effective than Procyclidine KEMADRIN, g placebo in improving motor function.1 American 2002 Maximum Dose: 500mg/day $82 To Ç salivation: reports of sublingual atropine eye drops, ς
W
KEMADRIN: Initial Dose: 2.5mg BID cc Çq5d $12 (2.5mg ), 5 mg tab ATROVENT nasal spray, po glycopyrrolate or botulinum toxin A. P L
‐ Neuropsychiatric & cognitive AE especially in elderly. Usual Dose: 2.5‐5mg TID cc $15‐20 2.5mg/5mL elixir Serious: Ç HR, delirium & psychosis Maximum Dose: 5mg QID cc $25 ‐ Withdraw very slowly to prevent PD exacerbations. DI: Worsen Parkinson’s sx with: antipsychotics, cholinergics Trihexyphenidyl ARTANE: Initial Dose: 1‐2mg HS Ç5qd $8 P L
‐ Switching to another anticholinergic may be of use. (eg. donepezil, galantamine, rivastigmine) ARTANE, g Usual Dose: 5mg BID to 2mg TID cc $12‐11 ς
ς Ç toxicity with: anticholinergics (eg. amantadine, TCA’s, OTCs) Maximum Dose: 5mg TID cc 2 , 5 mg tabs $15 82
PARKINSON'S DISEASE (PD): Drug Comparison Chart continued GENERIC/TRADE THERAPEUTIC USE / COMMENTS Brent Jensen BSP © www.RxFiles.ca Jul 13 CONTRAINDICATIONS CI / ADVERSE EVENTS AE / INITIAL, USUAL & MAXIMUM DOSE DRUG INTERACTIONS DI $/MON (Strength & formulations) NMDA (N‐methyl‐D‐aspartate antagonist) RECEPTOR ANTAGONIST: blocks reuptake/Ç release of dopamine Amantadine 54,55 SYMMETREL, g 100mg capsule 100mg/10mL syrup P L
9 PD: modest effect. Used early to help with tremor, later to È dyskinesia. May help “on” effect, better tolerated in young PD patients. 9 Antiviral‐influenza A, drug induced EPS Comments: ‐ 300 mg/day ↓dyskinesias~45% but lasted <8months.56 ‐ Likely safe & effective short term (& for up to 1 hour) for levodopa induced dyskinesias.57 ‐ Avoid abrupt withdrawal → worsen PD/cause NMS. AE: Common: CNS: (esp in elderly) confusion, drowsiness, nightmares, dizziness, insomnia; anticholinergic effects, irritability; GI upset, ÈBP, ankle edema & rose colored mottling on legs (livedo reticularis). Serious: seizures, psychiatric illness, arrhythmias, visual impairment, neutropenia, hallucinations & ÈBP. DI: antipsychotics: ÈPD effect & Èantipsychotic primarily typical effect; live influenza vaccine may be less effective; Ç amantadine levels with: triamterene Initial Dose: 100mg daily ↑7qdays Usual Dose: 100mg BID (8am & noon) ‐ TID Maximum Dose: 200mg BID $25 $41‐58 $75 Trial for ~2weeks before deciding if treatment ineffective.3 REVERSIBLE PERIPHERAL COMT (catechol‐O‐methyltransferase) INHIBITOR: È GI metabolism of levodopa to prolong t½ & AUC without affecting peak concentration, therefore Ç effect in the brain. Entacapone 58,59,60,61,62 COMTAN, g P L
200mg tab See levodopa section (pg 82) for STALEVO (carbidopa, levodopa, entacapone) info. Tolcapone TASMAR 200mg tab ‐Restricted for only previous pts due to of Ç LFT's. SAP phone #: 1‐613‐941‐2108 9 Idiopathic PD with wearing‐off symptoms at end of dose. Comments: ‐For motor complications to È off time ~1.5hrs/day (eg. end of dose wearing‐off), to È levodopa dose & modestly improves motor & disability.63, Cochrane 2004 ‐In pts who are not experiencing motor fluctuations while on levodopa, entacapone does not improve motor scores but improves some quality‐of‐life measures.64 ‐Combination with levodopa can Ç levodopa levels by ~25% thus È levodopa dose to minimize dyskinesias. This combination also prolongs levodopa’s effect. CI: dobutamine, dopamine, epinephrine, isoproterenol, MAOIs non‐selective, history of NMS. AE: Common: nausea, vomiting, Ç dyskinesias, urine/sweat discoloration orange, abdominal pain, Ç sweating initially, mood changes & daytime sleepiness. Serious: dyskinesia, ÈBP, diarrhea (may present even weeks to months after starting), hallucinations & NMS. ?? Ç prostate cancer & MI with STALEVO.FDA DI: ÇHR with dobutamine, dopamine, ephedrine, epinephrine & isoproterenol; chelates with iron; MAOIs a theoretical concern. Initial Dose: 100‐200mg with each l‐dopa dose $63‐76 Usual Dose: 200mg TID‐QID $157 Maximum Dose: 1.6g/day Administration: take with each levodopa dose given. CI: meperidine AE: Common: nausea, dizziness, ÈBP, abdominal pain, hallucinations, dyskinesia, rash, insomnia & alopecia. Serious: arrhythmia,ÇHR,ÇBP esp. with doses >10mg/day, anemia.
DI: Ç toxicity with: atomoxetine, amphetamines, bupropion, buspirone, dextromethorphan, entacapone, ephedrine, methylphenidate, miconazole, mirtazapine, phenylephrine,
pseudoephedrine, SSRI's, TCA's, venlafaxine. CI: cyclobenzaprine, dextromethorphan, other MAOIs, methadone, meperidine, propoxyphene, St. John’s Wort, tapentadol, tramadol. AE: Common: arthralgias, ÈBP, depression, dyspepsia, dyskinesia, falls hallucinations, headache. Rare: alopecia. DI: Ç CNS AE/serotonin syndrome: MAOI, SNRI, SSRI, TCA, mirtazapine, vasocontrictors. Ciprofloxacin Ç rasagiline levels. Initial Dose: 2.5‐5mg daily $19‐30 Usual Dose: 5mg daily‐BID with a meal $30‐53 Maximum Dose: 5mg BID $53 Administration: ‐ Give breakfast & lunch to È insomnia. ‐ Tyramine intake should not be a concern with typical doses. IRREVERSIBLE MONAMINE OXIDASE TYPE B INHIBITOR (MAO‐B): È dopamine metabolism Selegiline 65,66,67,68,69,70,71 P L
ELDEPRYL, g (Also known as DEPRENYL) 5ς mg tab W Rasagiline AZILECT 0.5, 1mg tab ⊗ P L
9 Adjunct for PD (may aid wearing off effects) Comments: ‐ Often used in earlier rather than later PD. ‐ Improves disability scores & delays need for Ç levodopa without Ç mortality;72,73 may È freezing? ‐ Has very mild symptomatic benefit with no definitive evidence for neuroprotection. 1, ADAGIO ‐ Ê Stop 10 days before anesthetic has amphetamine metabolites. 9 Idiopathic PD as monotherapy or as an adjunct levodopa Comments: ‐ May È off time. ‐ Often used in earlier rather than later PD. ‐ Caution: moderate‐severe liver/kidney impairment Initial Dose: 0.5mg if adjunct – 1mg daily $255 Ususal/Maximum Dose: 1mg daily $255 Mild impairment: max 0.5mg daily Administration: ‐ High fat meals È rasagiline levels. ‐ Theoretical tyramine BP crisis, but no dietary restrictions. =È dose for renal dysfx =È dose for liver dysfx ς=scored tab χ=Non‐formulary Sask =Exception Drug Status Sask. ⊗=not covered NIHB =prior NIHB W=covered by NIHB Ê=concern if given pre‐op 9=official indication ac=before meals AC=anticholinergic AUC=area under the curve BP=blood pressure cc=with meal CNS=central nervous system CR=control release d=day DA=dopamine agonist D1,2,3,4= dopamine receptors subtypes d/c=discontinue dx=disease EPS=extrapyramidal symptoms fx=function g=generic g=gram GI=gastrointestinal HR=heart rate HS=bedtime IR=immediate release l‐dopa=levodopa NMS=neuroleptic malignant syndrome n/v=nausea/vomiting PD=Parkinson's disease pt=patient SAP=Special Access Programme sx=symptoms tx=treatment t½=half‐life UPDRS=Unified Parkinson's Disease Rating Scale (0=no disability;176=total disability, max score Parts I‐III) wt=weight EPIDEMIOLOGIC: >100,000 Canadians, 0.4% general population, ~3% >65yr, lacks substantia nigra dopamine containing neurons. Website: www.parkinson.ca UPDRS scale: http://www.mdvu.org/library/ratingscales/pd/updrs.pdf SYMPTOMS: Resting Tremor: presenting feature
~70% of pts, rhythmic, asymmetric, hands (pill rolling), feet, lip or jaw (not usually head or neck). Rigidity: ~90% of pts, lead pipe, cogwheel often in neck, trunk & limbs. Micrographia: frequently present. Bradykinesia: hallmark ~70% of pts, slowness of all movements including walking. Postural Instability: often later presentation, shuffling gait, narrow base, festination, freezing & falls. DIAGNOSIS: classic‐one‐sided signs, resting tremor & good tx response. Atypical: ~20%, early falls, ÈBP, bladder dysfunction & lack resting tremor. 74
DRUG INDUCED: may take 2‐6 months to resolve; amphotericin, calcium channel blockers, chemotherapy, cholinergic, lithium, manganese, meperidine, metoclopramide, neuroleptics, reserpine, SSRI & valproate.
RED FLAGS: early severe dementia; prominent early instability; early autonomic dysfunction; no response to levodopa ~1g/d; presence of extra ocular movements, ataxia or corticospinal tract signs. RULE OUT: Alzheimer with EPS, essential tremor, corticobasal degeneration, diffuse Lewy body disease, drug‐induced EPS, focal lesions, infectious‐postencephalitic, multisystem atrophy postural hypotension, gait abnormalities, cerebellar ataxia, progressive supranuclear palsy early swallowing difficulties, gaze paresis, ? do olfaction test, vascular‐lacunar state & Wilson disease. Refer to Neurologist/movement disorder specialist. 75
ASSOCIATED PROBLEMS: depression nortriptyline, paroxetine, venlafaxine/anxiety/psychosis, ÈBP, neurogenic bladder, sexual dysfunction, dementia, dys‐arthia & ‐phagia, seborrheic dermatitis, sleep/ bowel changes. 76
77
ADJUNCT MEDS: Constipation: polyethylene glycol; Dementia: donepezil & rivastigmine but Ç N/V/ tremor; Daytime Sleepiness: modafinil W 200mg/d; Erectile Dysfx: sildenafil; ?Freezing/Fatigue: methylphenidate but abuse; Focal 78
79
80 81 82
83,DATATOP
Dystonia & Sialorrhea: botox; Off‐State Episodes: apomorphine SAP 2‐6mg SUBQ 3‐5x/d PRN with domperidone; Psychosis: clozapine W~6.25‐75mg/d quetiapine ~25‐150mg/d. Others: β‐blocker lack evidence; Vit E NO benefit.
NON‐PHARMACOLOGIC: for pt/family: education, support, exercise e.g. Tai chi, physiotherapy improve gait, speech tx improve volume, occupational tx for mobility, safety & driving skills; maintain social/family/work roles, nutrition counselling, & sleep hygiene. DISEASE PROGRESSION: may be more rapid if: onset >70yr, rigid, bradykinesia, dementia, or previous levodopa use but NOT as rapid progression if: male or resting tremor dominant. 1‐5 WEARING OFF: consider smaller & more frequent levodopa dosing liquid form option , add SINEMET CR, combine DA & levodopa, COMT inhibitor, amantadine, selegiline or apomorphine subq. (È protein in diet may help) 1‐5
DYSKINESIA: If bothersome, consider Èlevodopa dose (CR form hard to adjust dose), add amantadine, add/Ç/switch DA, possibly discontinue COMT/selegiline or consider surgery. TREMOR: if predominant, consider amantadine or anticholinergics especially in younger patients. 1‐5 DRUG INDUCED CONFUSION/HALLUCINATIONS: may take 1‐4 wk to resolve, Èmeds in following order: anticholinergic, selegiline, amantadine, DA & then l‐dopa. Consider quetiapine or clozapine after other offending drugs are d/c. 84,85 (DBS: STN, Gpi, Thalmic)
Tx when disability present, to control sx & Çfx, add meds slowly, good history & listen to sx timing; deterioration may be due to stress, Èsleep, new med or ?? H. pylori. If poor medical control consider surgery. 83
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Melanoma, Parkinson's disease and levodopa: causal or spurious link? A review of the literature. Melanoma Res. 2006 Jun;16(3):201‐6. Zanetti R, Rosso S. Levodopa and the risk of melanoma. Lancet. 2007 Jan 27;369(9558):257‐8. Zesiewicz, T. A., Sullivan, K. L., Arnulf, I., et al. AAN Practice Parameter: Treatment of nonmotor symptoms of Parkinson disease: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010 74: 924‐931. Guidelines AAN: Cheng EM, Tonn S, Swain‐Eng R, et al.; For the American Academy of Neurology Parkinson Disease Measure Development Panel. Quality improvement in neurology: AAN Parkinson disease quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology. Neurology. 2010 Nov 30;75(22):2021‐2027. http://www.neurology.org/content/75/22/2021.full.pdf+html Miyasaki JM, et al.; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence‐based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):996‐1002. http://www.neurology.org/cgi/reprint/66/7/996 Screening tools are available for depression and dementia in patients with PD, but more specific validated tools are needed. There are no widely used, validated tools for psychosis screening in Parkinson disease (PD). Clozapine successfully treats psychosis in PD. Cholinesterase inhibitors are effective treatments for dementia in PD, but improvement is modest and motor side effects may occur. Pahwa R, et al.; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence‐based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):983‐95. http://www.neurology.org/cgi/reprint/66/7/983 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B). Suchowersky O, et al.; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence‐based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):976‐82. http://www.neurology.org/cgi/reprint/66/7/976 1. Levodopa does not appear to accelerate disease progression. 2. No treatment has been shown to be neuroprotective. 3. There is no evidence that vitamin or food additives can improve motor function in PD. 4. Exercise may be helpful in improving motor function. 5. Speech therapy may be helpful in improving speech volume. 6. No manual therapy has been shown to be helpful in the treatment of motor symptoms, although studies in this area are limited. Further studies using a rigorous scientific method are needed to determine efficacy of alternative therapies. Suchowersky O, et al. Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence‐based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):968‐75. http://www.neurology.org/cgi/reprint/66/7/968 1. Early falls, poor response to levodopa, symmetry of motor manifestations, lack of tremor, and early autonomic dysfunction are probably useful in distinguishing other parkinsonian syndromes from Parkinson disease (PD). 2. Levodopa or apomorphine challenge and olfactory testing are probably useful in distinguishing PD from other parkinsonian syndromes. 3. Predictive factors for more rapid motor progression, nursing home placement, and shorter survival time include older age at onset of PD, associated comorbidities, presentation with rigidity and bradykinesia, and decreased dopamine responsiveness. Future research into methods for earlier and more accurate diagnosis of the disease and identification and clarification of predictive factors of rapid disease progression is warranted. Guidelines Canadian 2012: Young GB, Findlay JM, Benstead TJ, et al; Canadian Neurological Sciences Federation team. Canadian Guidelines on Parkinson’s Disease. Can J Neurol Sci. 2012 July;(39)4. Guidelines EFNS 2006: Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen JP, Lees A, Oertel W, Poewe W, Rascol O, Sampaio C, European Federation of Neurological Societies, Movement Disorder Society‐European Section. Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the EFNS and the MDS‐ES. Part II: late (complicated) Parkinson's disease. Eur J Neurol 2006 Nov;13(11):1186‐202. Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen JP, Lees A, Oertel W, Poewe W, Rascol O, Sampaio C, European Federation of Neurological Societies, Movement Disorder Society‐European Section. Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society‐European Section. Part I: early (uncomplicated) Parkinson's disease. Eur J Neurol 2006 Nov;13(11):1170‐85. Guidelines NICE 2006: NICE: National Institute for Health and Clinical Excellence ‐ Parkinson's disease: diagnosis and management in primary and secondary care. June 2006. http://www.nice.org.uk/nicemedia/pdf/cg035niceguideline.pdf. Guidelines SIGN 2010: SIGN‐Scottish Intercollegiate Guidelines Network‐Diagnosis and management of Parkinson's disease‐SIGN‐Jan 2010 http://www.sign.ac.uk/pdf/sign113.pdf