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N58 Neurology Toronto Notes 2023

Table 26. Common Medications - Major Issues

Indications Mechanism of Dosing Side Effects

Action/Class

Generic Name trade

Name

Contraindications

Epilepsy Start at 100-200 mg P0

once daily to IID.increase

by 200 mgfd up to 800-

1200 mg /d

Anticonvulsant

for partiali2’

generalization,

generalizedIonicclonic

Anticonvulsant for phenytoin

partial,tonic-clonic,

status epilepticus

carbamazepine Tegtelol 9 History of bone marrow

depression,hepatic disease, rash, agranulocytosis/aplastic anemia (rare)

hypersensitivity to the

drug,use of MAO inhibitor

inlast14 d

Hypersensitivity,pregnancy. Hypotension.SJS/TEN,SLE-type symptoms,gingival

breastfeeding:caution with hypertrophy,peripheral neuropathy.H/A.blood

dyscrasias.nystagmus, N.'V.constipation,sedation,

teratogenic

Drowsiness. H/A. unsteadiness,dizziness. M/V.skin

Dilantin1 100 mg P0 TID,

maintenance dose up to

200 mg P0 TID

SE:10-15 mg/kg IV loading

dose then maintenance

P-450 interactions

doses ol 100 mg P0 or IV

q6 8 h

Depakene 10 -15 mg/kg/d POin

Apo Valproic 9

divided doses,increase

incrementally until

therapeutic dose to max of

60 mg/kg/d

2arontin» 500 mg/d P0,increase by

250 mg every 4-7 d to max

1.5 g/d in divided doses

Hyperscnsitivrty.hepatic Hepatic failure,H/A. somnolence, alopecia. M/V.

disease,urea cycle disorders diarrhea, tremor,diplopia,thrombocytopenia,

hypothermia,pancreatitis,encephalopathy,most

leratogenicAED (dose-dependent)

Anticonvulsant valproic acid

lor partial or

generalized,absence

seizures

Anticonvulsant for ethosuximide

absence seizures

CHS depression,blooddyscrasias,SIE.SJS.61

symptoms

Hypersensitivity

(succinimides)

Stroke

Preventionin

AtrialFibrillation

Anticoagulant (direct dabigatran

thrombin inhibitor)

Pradaxa!

110 mg P0 BID or 150 mg CrCI

'

30ml/min.significant Dyspepsia,gastritis,bleeding

hemostatic impairment,or

CNS lesions within 6 mo with

high-risk of bleeding

Concomitant anticoagulant. Bleeding

hepatic disease,pregnancy,

strong CYP3A4 and

P glycoprotein inhibitorse.g.

itraconazole,ritonavir

Active bleeding,

gastrointestinal bleeding,

recent cerebral inlardion,

active peptic ulcer disease

with recentbleeding.

hepatic disease with

coagulopathy

Active bleeding,hepatic Bleeding

disease,CrCI <30ml/min

Hypersensitivity todonepezil Diarrhea,N/V.insomnia,muscle cramps,fatigue,

or to piperidine derivatives anorexia, HTN,syncope,AV block

P0 BID

Anticoagulant (Factor rivaroxaban

Xa inhibitor)

Xarelto - 15 mg PO once daily or 20

mg P0 once daily

Anticoagulant (Factor apixaban

Xa inhibitor)

Eliquis' 2.5 mg P0 BID or 5 mg Bleeding (conjunctival,gastrointestinal, gingival,

NII0 contusion,hematoma,epistaxis,hematuria)

Savaysa 1 30 mgP0 or 60 mg P0

once daily

5 mg POonce daily,may

increase to10 mg P0 once

daily after 4-6 wk

Anticoagulant (Factor edoxaban

Xa inhibitor)

Cholinesterase donepezil

Inhibitor

Mild to Moderate

Alzheimer's

Disease or

Dementia with

Lewy Bodies

Aricept

-

Multiple Sclerosis MS Disease Modifying interferon-fMb

therapy

Bclaseron

inlerferon -p -la SC Rebil '

interferon p la IM Avonex '

Pregnancy,hypersensitivity Injection site reactions,injection site necrosis,flu-like

lo natural or recombinant

interferon-0

0.25 mg (8 MU) SC every

other day

44 pg SC 3 times/wk

30 pglM once weekly

20 mg SC once dally

symptoms (fever,chills,myalgia:tend to decrease

over time)

MS Disease Modifying glaliramer acetate Copaxone

Therapy

MS DiseaseModifying natalizumab Tysabn

Therapy

Hypersensitivity to

glaliramer or mannitol

Hypersensitivity

lo natalizumab,

progressive multilocal

leukoencephalopathy (PML)

Hot available

Injection site reactions, nausea,transient chest pain,

vasodilation

Rash,nausea,arthralgia,H/A.infections,rare risk of

PMl and melanoma

300 mg IV given over 1h.

every 4 wk

MS Disease Modifying fingolimod

Therapy

Muscle Relaxant- baclofen

Antispastic

6ilenya:

0.5 mg P0 once daily Diarrhea, transaminitis,H/A.bradyarrhylhmia.

lymphopenia

Hypersensitivity lobaclofen Transient drowsiness,daytime sedation,dizziness.

weakness,fatigue,convulsions,constipation,nausea

Spasticity (Le. lioresal'

5mg P0 TID,increase by

15 mg/dq3dto max dose

80 mg/din three divided

doses

MS)

SJS:Stevens-Johnson Syndrome,US: toxic epidermal necrolysis

r i

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N59 Neurology Toronto Notes 2023

Landmark Neurology Trials

Trial Name Reference Clinical Trial Details

Stroke

NASCET NEJM 1991:7:445- Title:Beneficial Effect olCarotid Endarterectomy inSymptomaticPatients with High-Grade CarotidStenosis

Purpose:To assess the efficacy of carotid endarterectomy for reducing stroke risk inpatients witha recent adverse cerebrovascular event and ipsilateral carotid

stenosis.

Methods:659patients with recent|

'

120d)hemispheric or retinal TIAor nondisablingstroke with70-99%stenosis received optimal medical care.Those

assigned tosurgical treatment underwent carotid endarterectomy.

Results:Esumated cumulative risk of any ipsilateral stroke at 2yr was 26%inmedical patientsand9%insurgical patients (absolute risk reduction,17%;

P<0.001).and13.7%and 2.5%,respectively,for major or fatal ipsilateral stroke (10.6%:P'

0.001).

Conclusion Carotid endarterectomyeffedively reducesstroke risk in patients with arecent adverse cerebrovascular event and ipsilateral carotid stenosis.

Title:Tissue Plasminogen Activator forAcute IschemicStroke

1995:333:1581- Purpose:To investigate the clinical efficacy of IV rtPAinacute ischemic stroke.

Methods:Patients withacuteischemic stroke randomly assigned to receive rtPA or placebo.

Results:At 24hr.therewas no significant dilferencesin neurologic improvement between rtPA andplacebo.Clinical benelilolrtPAwas observed at 3mo for all

outcome measures.Patientstreated with rtPA were 30%less likely tobe disabledat 3mo.rtPA was associated withsignificantly more symptomatic intracerebral

hemorrhage within 36h after stroke.

Conclusion:When administered within 3h ol ischemic stroke,rtPA improvedclinical outcomes despite a greater risk of symptomatic intracerebral hemorrhage.

Title:Comparison ol Warlarin and Aspirin lor Symptomatic Intracranial Arterial Stenosis

Purpose: To compare the safety and efficacy ol warlarin and aspirin in the treatment ol stroke caused by atherosclerotic intracranial arterial stenosis.

Methods: 569 patients with TIA or stroke caused by 50-99% stenosis were randomized to receive waifarin(target international normalized ratio,2.0-3.0) or

aspirin (1300 mg/rf).

Results:Study stopped early due to salety concerns. Adverse events included death(4.3%on aspirin vs.9.7% on warlarin;P-0.02),major hemorrhage (3,2%vs.

8.3%;P-0.01J. and Mlor sudden death (2.9% vs.7.3%;P-0.02) during1.8 yr mean lollow-up.

Discussion:In patients withintracranial arteiial stenosis,

warlarin afforded noclinical benefit and was associatedwith more adverse events.Aspirin is thus preferable.

53

NIHDS rtPA NEJM

87

WA5I0 NEJM

2005:352:1305

16

SPARCl NEJM Title:High-Dose Atorvastatin alter Stroke orTransient Ischemic Attack

2006;355:549-59 Purpose:To investigate whether statins reduce the risk of stroke alter a recent stroke or TIA.

Method:4731patients with strokeor TIA within1-6mo and LOL-2.6-4.9 mmol/L and without coronary disease were randomly assigned to receive 80 mg

atorvastatin daily or placebo.

Results:Fatal oc nonlalal stroke occur edin11.2% olpatients receiving atorvastatinand13.1%recerving placebo (5-yr absolute reduction in risk,2.2%;adjusted

hazard ratio,0.84:95%Cl,0.71to 0.99:P-0.03).The atorvastatin group experiencedrelativelymorehemorrhagic strokes (hazard ratio1.66 (1.08-255)).

ConclusionAtorvastatin reduced the overall incidence of strokes in patients withrecent strokeor TIA.despite anincrease inrates of hemorrhagic stroke

Title:Thrombolysis WithAtteptase3 to 4.5 Hours After Acute IschemicStroke

2008:359:1317- Purpose:To investigate theefficacy and salety of aiteplaseadministered 3-4.5 h followingstroke onset

Methods:Randomly assigned 821patients with acute ischemic stroke toreceive IValteplase [0.9 mgfkg) or placebo.Primary outcome was disability at 90d

(favorable outcome:0-1on modified Rankin scale) or unfavorable outcome (2-6).

Results:Aiteplase wasassociated with more favourableoutcomes than placebo (52.4%vs.45.2%:OR.1.34:95% Cl,1.02-1.76;P-0.04).Intracranial hemorrhage

wasmorefrequent on aiteplase vs.placebo (27.0% vs.17.6%;P-0.001).Ho significantdifferenceinmortality or adverse events.

Conclusion:In patients with acute ischemic stroke,IV aiteplase administered 3-4.5h after symptom onset significantly improved clinical outcomesbut also

increased the frequency of ICH.

Title:Oabigatran Versus Warfarin inPatients with AtrialFibrillation

Purpose:To investigate the efficacy and salety of dabigalran vs. warfarininpreventing stroke or systemic embolism in patients with AFib

Methods: 18,113 patients with AFib and risk of stroke were randomly assigned loreceive dabigatran110-150mgBID or adjusted-dose warfarin.

Results:Rates ol stroke or systemic embolism were1.69%/yr on warlarin and 1.53%/yr on110 mgdabigaIran (relative risk with dabigalran,0.91:95%Cl,

0.74-1.11) and 1.11 /yr on 150 mg dabigatran (0.66 (0.53-0.82)).Frequency of major bleeding was 3.36Vyr on warfarin and 2.71%/yr on 110 mg ol dabigalran

(P-0.003) and3.11%/yr on 150mg dabigalran (P-0.31).

Conclusion:When comparedlo warlarin,dabigalran has potential to lower stroke rates or major hemoirhage depending on dose.

Title:Stenting Versus Endarteiectomy lor Treatment ol Carotid-Artery Stenosis

2010:363:11-23 Purpose:To investigate the ellicacy and salety olcarotid-artery stenting vs.carotid endarterectomy tor treating carotid-artery stenosis.

Methods: 2502patients with carotid stenosis wererandomly assigned to carotid-artery stenting or carotid endarterectomy.Primary composite outcome was

Ml,stroke,or death from any cause or any ipsilateral stroke within 4yr.

Results:Estimated 4 -year rates of theprimary outcome did not significantly differ between stenting andendarterectomy (7.2%vs. 6.8%;hazard ratio with

stenting.1.11(0.81-1.5(1:P-0.51).Rates ol individual endpoint components for stenting vs.endarterectomy were 0.7%vs.0.3%,P-0.18 lor death; 4.1% vs.2.3%,

P-0.01for stroke:and1.1%vs.2.3%,P-0.03 tor Ml.

Conclusion:Composite primary outcome risk did not differ significantly between stentingandendarterectomyinpatients withcarotid stenosis.

Title:Apixaban Versus Warlarin in Patients With Atrial Fibrillation

2011;365:981-92 Purpose:To assess theefficacy of apixaban in reducing the risk of stroke as comparedto warfarin.

Methods:18.201patients with AFib and one additionalrisk factor for stroke were randomizedtorecedeeither apixaban or warfarin.The primary outcome was

stroke or systemic embolism.

Results:The rateotstrokeor systemic embolism was lowerin the apixaban group thanin the warlarin group (1.27% vs.1.60%;P'

0.001lornoninleriority,

P-0.01for superiority).The ratesof major bleeding (2.13%vs.3.09%:P'

0.001) and death (3.52%vs.3.94%;P-0.047) were lower in theapixaban group than in

the warfarin group.

Conclusion:Inpatients with AFib,apixaban was superior to warfarin for preventing stroke or systemic embolism withlower rates olmajor bleeding and death.

Title:Apixaban inPatients withAtrial Fibrillation

2011:364:806-17 Purpose:To investigate the efficacy and salety of apixaban in preventing strokeinpatients with AFib.

Methods: 5599 patients with AFib at increased risk lor stroke and who were unsuitablelor vitamin Kantagonist therapy were randomly assigned to receive 5 mg

apixabanBID or aspirin(81-324 mg daily).

Results:Study terminated early due to cleat apixaban benefit. Rates of stroke or systemic embolismwere 1.6%/yron apixaban and 3.7%/yr on aspirin (hazard

ratio withapixaban.0.45 (0.32 to0.62);P'

0.001). There were no significant dilterences inrates olmajor bleedingor intracranial bleeding.

Conclusion:Apixaban reduced therisk of stroke or systemic embolism without increasing bleeding or hemorihageriskinpatients with AFib unsuitablelor

vitamin K antagonists.

Title:Rivaroxaban Versus WarfarinInNonvalvular Atrial Fibrillation

2011;365:883-91 Purpose: To investigateilrivaroxaban isnoninlerior to warlarininpreventing stroke or systemic embolisminAFib.

Methods: 14.264 patients with nonvalvular AFib at increased risk for stroke were randomly assigned to receive either rivaroxaban (20 mg/d) or dose-adjusted

warfarin.

Results:Rates ol stroke oc systemic embolism were1.7%/yr onrivaroxaban and 2.2%/yr on warlarin(hazardratio.0.79 (0.66 to 0.96);P<0.001lor

noninteriocityl.Significant reductions in ICH (0.5% vs.0.7%.P-0.02) and fatal bleeding (0.2% vs.0.5%. P-0.003) were seen in the rivaroxaban group.

Conclusion:Rivaroxaban was noninferior to warlarin in patients with AFib for preventing strokeor systemic embolism with lower risks of ICH and fatal bleeding.

ECA5S 3 NEJM

25

RELY NEJM

2009:361:1139-51

CREST NEJM

ARISTOTLE NEJM

AVERROES NEJM

ROCKETAF NEJM

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N60 Neurology Toronto Notes 2023

Trial Name Reference Clinical Trial Details

Title:Stenting Versus Aggressive Medical Therapy lor Intracranial Arterial Stenosis

2011:365:993- Purpose: To compare theetlicacy olpercutaneous transluminal angioplasty and stenting (PTAS) vs.medical management inintracranial arterial stenosis.

Methods:451patients withrecent TIA orstroke attributed to 70-99% stenosis were randomly assigned to aggressive medical management plusPTAS or

aggressive medical management alone.

Results:30-day strokeor death rate was14.7% and 5.8% in the PTASandmedical-management group,respectively (P-0.002).1-yr ratesof theprimary end

point (stroke or death within 30 dor alter a revascularization during follow-up or stroke in the territory of the qualifyingartery beyond 30d) were 20.0% in PTAS

and12.2%Inmedical-management (P-0.009).

Conclusion:Aggressive medical management inpatients with Intracranial arterial stenosis was superior to PTAS.

Title:RapidBlood-Pressure Loweringin Patients with Acute IntracerebralHemorrhage

2013:368:2355- Purpose:To investigate theefficacy of rapidlowering of elevatedBPfor improving outcomes inpatients with intracerebralhemorrhage.

Methods: 2839patients with spontaneous intracerebral hemorrhage andelevated sBP were randomly assigned to receiveintensive treatment (target sBP*

140

mmHg within1hr) or guideline-based treatment (target sBP'

180 mm Hg).

Results:52.0% receiving intensive treatment vs. 55.6%receiving guideline-based treatment experienced a primary outcome event (death or major disability)

J

0R. 0 87 (0.75-1.01): P-0.06). Intensive treatment was associatedwith signilicantly lower modiliedRankin scores(OR for greater disability.0.87 (0.77-1.00):

Conclusion: Intensive BPlowering inintracerebral hemorrhage didnolsignificantly reducerates of death or severe disability but may improve functional

outcomes.

SAMMPRIS NEJM

1003

IIITERACT2 NEJM

69

Title:Randomized Assessment oi RapidEndovascular Treatment of Ischemic Stroke

2015:3721019-30 Purpose: To investigate rapidendovascular treatment plus standard careinacute ischemic stroke with a proximal intracranial arterial occlusion,small infarct

core,andmoderate-good collateral circulation.

Methods 316 patients randomly assigned to receive endovascular treatment with the use of available thrombectomy devicesplus standard of cate (intervention

group) or standardcare alone (control group).

Results:The intervention reduced mortality 110.4%.vs.19.0%in controls:P-0.04) and was associated withimproved scoreson the mod

days (common OR.2.6:95%CI,1.7 to 3.8:P^O.001).

Conclusion:Rapid endovascular treatment improved functional outcomes andreduced mortality inselect patients with acute ischemicstroke.

ESCAPE NEJM

died Rankin scale at 90

MR CLEAN Title:A Randomized Trial olIntraarterial Treatment for AcuteIschemic Stroke

2015:372:11-20 Purpose: To investigate tuictional outcomes of intraarterial treatment lor emergency revascularizationinpatients with acute ischemic stroke caused by a

proximal intracranial arterial occlusion.

Methods:500 patients that could be treated intraarterially within6h alter symptom onset were randomly assigned toelther intraarterial treatment plus

standard care or standard care alone.

Results:The rate of functional independence (modified Rankinscore.Oto 2) was higherin theintervention group (32.6%vs. 19.1%;absolute difference,13.5%,

95% CL 5.9 to 21.2).Rates of mortality or symptomatic intracerebral hemorrhagewere nolsignificantly differentbetween groups.

Conclusion:Intraarterial treatment within 6 h following stroke onset was safe and effectiveinacute ischemic stroke caused by intracranial,proximal arterial

occlusion olthe anterior circulation.

Title:Thrombectomy 6 to 24 Hoursafter Stroke with a Mismatch betweenDeficit and Infarct

Purpose: To Investigate theetlicacy and safety olendovascular thrombectomy performed > 6 h following ischemic strokeonset.

Methods:206patients with acute stroke who were well 6-24 hours earlier with mismatch between clinical deficit and infarct were randomly assigned to

thrombectomy plus standard care or standardcare alone (control).

Results:At 90 d.mean scores on a modified Rankin scale were 5.5 in thrombectomy and 3.4in controls(adjusted difference,2.0 points(1.1-3.0):posterior

probability of superiority,H3.999).and the rateof functional independence were 49% and13%,respectively (adjusted difference,33%(24-44):posterior

probability of superiority,>0.999).

Conclusion: Adding thrombectomy tostandard of care improved disability outcomes inpatients withacute stroke who were well6-24 hoursearlier with clinical

deficit and infarct mismatch.

NEJM 18:379:215- Title:C!opidogrel and Aspirin in AcuteIschemic Strokeand High-Risk TIA

Purpose:Toinvestigate the efficacy of dopidogrel plus aspirin toreduce therateof stroke recurrence during the first 3 months following a minor ischemic stroke

or TIA.

Methods:4881patients with minorischemic strokeor high-risk TIA wererandomly assigned todopidogrel plusaspirin or aspirin plus placebo.

Results:Tewer major ischemic events wereobserved in those receiving dopidogrel plus aspirin|5%) vs.aspirin plus placebo (6.5%)(hazardratio.0.75 (0.59-

0 95);P-0.02). Risk of major hemoirhage was greater in those receiving dopidogrel plus aspirin (0.9%) vs. those receiving aspirin plus placebo (0.4%) (2.32

(1.10- 4.87);P-0.02),

Conclusion:Clopidogrel plusaspirin lowers riskolmajorischemic events butincreases risk olmajor hemoirhagein patients with minorischemic strokeor

high-risk TIA.

NEJM

DAWN NEJM

2018:378:11 21

POINT

25

Multiple Sclerosis

Interferon-p-lb

isdietlive in

relapsingremitting

multiple sclerosis.

I.Clinical results

of a multicenter,

randomized,

double-blind,

placebo-controlled

trial.The IENB

Multiple Sclerosis

Study Group.1993

PreCISe

Neurology Title:lnterferon-p-1b is effective in relapsing-remitting multiple sclerosis.I.Clinicalresults ol a multicenter,randomized,double-blind,placebo-controlled trial.

1993:43:655-61 The IfNBMultiple Sclerosis Study Group

Purpose: To Investigate the efficacy of Interferon (3 -1b (IFIIB) in relapsing-remittlng MS.

Methods: 372 ambulatory patients with relapsing-remitting MS sell-administered either placebo.1.6million international units (MIU) olIFNB.or 8 Mill ol IFIIB.

Results:After 2 yr,rates of annual clinical exacerbation for patients on placebo were 1.27:1.17 lor 1.6 MIU IFNB:and0.84 lor 8 MIU IFIIB.indicating both

treatment groupsperformedsignificantly better thanplacebo.In the 8MIU group,there wasa twofoldreductioninthe frequency of moderate-severe attacks.

Conclusion:Interteron-jHbreduces relapserate andseverity of relapsesinrelapsing-remitting MS.

Title:Effect of filatiramer Acetate on Conversion to Clinically DefiniteMultipleSclerosis inPatients with Clinically IsolatedSyndrome (Precise Study):A

2009:374:1503-11 Randomised,Double-Blind,Placebo-Controlled Trial

Purpose:Toassess the efficacy of early treatment withglatiramer acetatein delaying onset of clinically definite MS

Methods: 481patients with clinically isolated syndrome withunifocal manilestation. and >212-weighted brain lesions -6 mm,receivedSC glatiramer acetate

(20 mg/d) or placebo for upto 36months.

Results:Relative toplacebo,therisk ol developing clinically definite MS was reduced by 45% withglatiramer acetate(hazardratio 0.55.95% Cl0.40-0.77;

P-0.0005).It prolonged dietime for 25% of patients to convert to clinically definite disease by115%.Injection-sitereactions and immediatepost-injection

reactions were the most common adverse events.

Conclusion: In patientspresenting with clinicalyisolated syndrome and brain lesions,conversion to clinically definiteMS can bedelayedby early treatment with

glatiramer acetate.

Lancet

r“i

L J

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N61 Neurology Toronto Notes 2023

Trial Name Reference Clinical Trial Details

Seizure Disorders and Epilepsy

Title:Immediate Versus Deferred Antiepileptic Diug Treatment for Early Epilepsy andSingle Seizures:A RandomisedControlled Trial

2005:365:2007- Purpose: To investigate the relativebenefits and risksof initiatingor withholding antiepileplic drug trealmenl inpatients with few or infrequent seizures.

Methods: 1443 patients with single seizuresor early epilepsy were randomly assigned to leceive either immediateor deferred antiepileplic drug treatment

Results:Immediate treatment prolonged time to1st seizure (hazardraiiol.4;(95%Cl 1.21.7)),2nd seizure<1.3(1.1-1.6)).and first tonic-clonic seizure (1.5 (1.2-

l.8|). Time to 2-yr remission of seizures was reduced by immediate treatment (P-0.023). The proporlion olpatients that were seizure-tree between years 3-5

were 76%on immediate treatment and77% on deleried treatment.

Conclusion:Inindividuals with singleor infrequent seizures,seizure occurrence in the first1-2 yr isreduced by immediate antiepileptic drug treatment,but

long-term remission is not affected.

Title:The SANAD Study of Effectivenessof Valproate,lamotrigine,orTopiramate for Generalisedand Undassifiable Epilepsy:An Unblinded Randomised

ControlledTrial

Purpose:To investigate thelong-term effects of valproate,lamotrigine.and topiramale in patients with generalized onset seizuresor seizures that are not easily

classified.

Methods: Between1999-2004 during theinitial trial,patients were randomly assigned toreceive valproate,lamotrigine,or topiramate,and follow-up data

were obtained up to 2006.

Results:Valproate was significantly better than topiramate for time to treatment failure (hazard ratio1.57 (95%Cl1.19-2.08)). and significantly belteiIlian

lamotrigine foi lime lo 12-mo remission (0.76 (0.62-0.94)).

Conclusion:Valproate should remainthelirst line therapy lor generalised andunclassified epilepsiesdue to superior eflicacyand safety profiles.

MESS Lancet

13

SAIIAD lancet

2007:369:1016-

26

Alzheimer's Disorder

Am J Psychiatry

2011:168:831-839

CATIE-AD Title:Cognitive Effects of Atypical Antipsychotic Medications inPatients withAlzheimer's Disease:Outcomes from CATIE-AD

Purpose:Toexamine the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trialsof theIntervention EffectivenessAlzheimer’s Disease study.

Methods:421outpatients withAlzheimer's disease and psychosis or agitatediaggressive behaviour were randomized to receiveolanzapine,gueliapine.risperidone,

or placebo in a multicentre double -blinded RC1. MMSE and Alzheimer’s Disease Assessment Scale|ADAS|scores were measured at 36 wk.

Results:Patients receiving atypical anlipsycholKscxhlbileda faster late ol cognitive decline as measured by MMSE scores!- 0.067/wk vs. 0.007/ wk). They also

had a significantly faster decline computed loplacebo on a composite measure of ADAS. MMSE. and various other cognitive tests ( O.OIVwk vs. 0 OOlAvk).

Conclusions Long leiin useol atypical anlipsychotics for behavioural symptoms andpsychosis in dementia patients is associated with greater rates olcognitive decline.

Neuropathic Pain

A Vaccine to

Prevent Herpes

Zoster and

Postherpetic

Neuralgia inOlder

Adults. Oxman et

al. 2005

NEJM Title:A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults

2005;352:2271- Purpose:Toinvestigate whethervaccinalion against herpes zoster would decrease the incidence and/or severity ol infection or PHH in older adults.

Methods:38.546 adults aged 60yr were randomized to receive live attenuatedOka/Merck VZV vaccine (zoster vaccine) or placebo.

Results:Vaccination reduced herpes zoster dlness burden by 61.156 (P'

0.001),incidence ofinfection by 51.3% (P- 0.001). and incidence of PHN by 66.5% (P'

0.001).

Conclusion:Among older adults,the zoster vaccine significantly reducedmorbidity from herpes zoster and postherpetic neuralgia.

;/ !

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