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GuidelinesformanagementofessentialtremorPalPKAnnIndianAcadNeurol

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GUIDELINES
Year:2011|Volume:14|Issue:5|Page:2528

Guidelinesformanagementofessentialtremor
PramodKumarPal
DepartmentofNeurology,NationalInstituteofMentalHealthandNeurosciences,Bangalore,India
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14Jan2011
21Jul2011

CorrespondenceAddress:
PramodKumarPal
DepartmentofNeurology,NationalInstituteofMentalHealthandNeurosciences,Bangalore
India
SourceofSupport:None,ConflictofInterest:None

DOI:10.4103/09722327.83097

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Howtocitethisarticle:
PalPK.Guidelinesformanagementofessentialtremor.AnnIndianAcadNeurol201114,SupplS1:258
HowtocitethisURL:
PalPK.Guidelinesformanagementofessentialtremor.AnnIndianAcadNeurol[serialonline]2011[cited2016May
3]14,SupplS1:258.Availablefrom:http://www.annalsofian.org/text.asp?2011/14/5/25/83097
Essentialtremor(ET)isacommonmovementdisorder,andapproximately50%ofthecasesareinheritedasan
autosomaldominanttrait.[1]TheincidenceofETincreaseswithage,maymanifestatanyage(childhoodtoadulthood),
andthosewithapositivefamilyhistoryhaveanearlierageofonset.[2]Thetremorinvolvesmainlytheupperlimbs
distallyandisposturalorkinetictype.Thelesscommonpartsinvolvedwithtremorarethehead,lowerlimbs,voice,
tongue,face,andthetrunk.Thetremoramplitudeincreaseswithtime,andpatientsexperiencedifficultyinwriting,
eating,holdingobjectsanddoingfinemotortasks,dressing,andspeaking.[3]AlthoughETusuallydoesnotreducelife
expectancyorcauseothersymptoms,manypatientshaveseverepsychosocialdisability.[3]Tremoroftenincreaseswith
anxiety,stress,andinsituationsinvolvinginteractionwithothers.Patientswithheadandvoicetremoroftensuffersevere
embarrassments,andmaydevelopdepression.

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QualityManagementSystem
DrugTreatment
FlowChart

ETshouldbedifferentiatedfromtheothertypesoftremors,especiallytremorofParkinson'sdisease,tremorassociated
withhyperthyroidism,anddystonictremorofheadinpatientswithisolatedheadtremor.Onceadiagnosisismade,the
severityoffunctionalandpsychosocialdisabilitiesshouldbeassessedbyobjectivescales,whichwillhelptodetermine
theneedforpharmacotherapy.
ThemanagementofapatientwithETincludes(a)behavioraltechniquesandphysicaltherapy,(b)medicaltherapy,and
(c)surgicaltreatment.Thepatientshouldbeexplainedaboutthedisease,thelongtermoutcome,andwhatthetherapies
canachieve.Alltherapiesareessentiallysymptomaticandwillnotcureorchangethecourseofthedisease.Ifthereis
minimalfunctionaldisability,thepatientneednottaketreatment.Evenifthetremoriscontrolledbymedicaltherapy,
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stressandanxietycanincreasethesymptoms.AnoutlineofthemanagementofETisgivenin[Figure1].
Figure1:Aflowchartshowingthestepsinthemanagementofessentialtremor
Clickheretoview

BehavioralTechniquesandPhysicalTherapy

NotallpatientswithETwillneedtreatmentwithdrugs.Treatmentdependsontheseverityoftremor,thebodypart
affected,andtheoccupationofthepatients.Itisalsodeterminedbythedegreeofsocialdisability.Inpatientswithless
disablingtremor,certainbehavioraltechniquesandphysicaltherapymaybeuseful.Theseincluderelaxationtherapies
andreducingemotionalstress,usingthelessdisabledhandtowriteoreat,usingwristweights[2]andminimizing
exposuretotremorogenicfoods(eg,caffeine)anddrugs(eg,sympathomimetics).
MedicalTreatment

Treatment
for
Huntington
Advanced stem
cell treatment
for Huntington
Disease

Treatmentschedules
Whenitisdecidedtostartmedicaltreatment,itcanbeof2types:
1.Intermittenttreatment:Onanasneededorscheduledbasis.Thisisrecommendedwhenthepatientisdistressed
mainlyinsocialgatheringsorpriortoanimportantsocialactivity.Ahalfto2tabletsofpropranolol(20mg)canbe
administered30minto1hbeforeasocialactivityortheanxietyprovokingevent,whichincreasestremor.
Alternatively,abenzodiazepine,suchaslorazepamorclonazepamcanbeadministeredprophylactically.However,
asthebenzodiazepinescancausecentralnervoussystemadverseeventsandalsohaveabusepotential,theyneedto
beadministeredjudiciously.Althoughroutineuseofalcoholisnotrecommended,inpatientswithalcohol
responsivetremors,judicialuseofasmallamountofalcoholpriortoselectsocialactivities,suchassocialdinner,
canbeconsidered.
2.Aslongtermsuppressivetherapy:Inpatientswhoneedlongtermtherapy,thefollowingdrugshaveprovedtobe
usefulwithvariedefficacyandlevelsofrecommendations,basedontheclassofevidence.

Drugsofchoice
Blockers,mostcommonlypropranolol,andprimidonearethedrugsofchoicefortreatmentofET.Boththeseagents
havelevelArecommendation,andeithercanbeusedforinitialtreatmentofET,[4]dependingontheconcurrentmedical
conditions,andpotentialsideeffects.
Propranolol(2blocker)
Treatmentshouldbeinitiatedat10mgoncedailyandgraduallytitrated(eg,every37days)to20mgtwicedaily.Elderly
individualsmayneedalowerdose(eg,10mgtwicedaily),whileforthosewhoaretoleratingwell,propranololcanbe
increasedupto240mg/dayindivideddoses.Improvementoccursinapproximately50%60%ofthepatients,the
greatestimprovementbeingforhandtremor,andtheleastforheadorvoicetremor.Longactingpreparationsof
propranololalsohaveasimilarefficacy.Tento15percentoftherespondersmaydeveloptoleranceafterayearof
treatment.[5]Sideeffectsincludelightheadedness,fatigue,impotence,bradycardia,andreducedbloodpressure.Relative
contraindicationstopropranololaresevereheartfailure,conductionblocks,hyperactiveairwaydisease,depression,and
diabetes.
Primidone
TheefficacyofprimidoneformanagingETappearstobesimilartopropranolol[5]anditcanbeaninitialtherapy,
althoughmostoftenthisisstartedafterthefailureofpropranololtocontrolETsatisfactorily.Currently,thisdrugisnot
easilyavailableinIndia.Thetreatmentisinitiatedatthelowestpossibledoseandgraduallytitrateduptoavoidside
effects,whichoftenappear.Whena50mgtabletoranoralsuspensionpreparation(50mg/mL)isavailable(notavailable
inIndia),itcanbestartedat12.5mgatbedtimeandslowlytitratedupward(incrementsby12.5mgeveryweek)tothe
dosewhendesirabletremorcontrolisachievedwithoutsignificantsideeffects.Mostpatientsachieveanoptimaltremor
controlat250mg/day,althoughhigherdosesupto7501000mg/daymaysometimesberequired.Whenapatient
requiresalowerdose,oncedailydosingmaybeadequatewithhigherdosage,thedrugshouldbegivenin3divided
dosages.InIndia,sinceonly250mgtabletsareavailable,thetreatmentisusuallystartedwithonequarterofatablet(or
evensmalleriffeasible)atbedtime,andgraduallyincreasedbyonequartereveryweek,tillthetremorcontrolis
achieved(thefinaldosemaybegivenin3divideddosages).Whenthepatientcannottolerateanyincrementofdosage,
hemaycontinuethepreviousdosageforalongertime,andthentryfurtherincrementofdosage.
Themostcommonsideeffectofprimidoneissedationanddrowsiness,andtheothercommonsideeffectsbeingnausea,
vomiting,dizziness,ataxia,confusion,vertigo,andacutetoxicreaction.Patientsonprimidoneshouldhaveacomplete
bloodcountbeforestartingthetreatmentandagainevery612months,asithasbeenreported,althoughrarely,tocause
redcellhypoplasia,aplasia,agranulocytosis,andmegaloblasticanemia.Itiscontraindicatedduringpregnancy,lactation,
andinpatientshavingporphyriaandhepaticandrenaldysfunctions.
Combinationtherapy
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Whenmonotherapywithpropranololorprimidonedoesnotadequatelycontrollimbtremor,these2drugscanbeusedin
combination.Ithasbeenshownthattheremaybeanaddedbeneficialeffectwithoutanincreaseinsideeffects.[4]
Otherdrugs
Thefollowingdrugshavelowerlevel(levelBorC)recommendationsfortreatingET,andshouldbetried(addonor
monotherapy)inpatientsnotadequatelyrespondingtopropranololorprimidone,orwhenthereareprominentside
effects:
Benzodiazepines
Thisgroupofdrugs,whichprobablyaugmentsGABAactivity,canbeusedasaddontreatmentforET.Alprazolam
(0.1253mg/day),clonazepam(0.56mg/day),lorazepam(110mg/day),anddiazepam(110mg/day)canbeconsidered
inpatientswithsignificantworseningoftremorduetoanxietyoremotionalstress.Clonazepammaybeparticularly
usefulfortreatmentoforthostatictremor,ararevariantofET.[6]Thedrugsshouldbeusedwithcautionbecauseoftheir
abusepotential,sideeffectsofdrowsinessandfatigue,andpossiblewithdrawalsymptomsfollowingabrupt
discontinuance.
Gabapentin
Gabapentin(structuresimilartoGABA)canbeusedasamonotherapyorasanaddontherapyfortreatmentofET.[7],[8],
[9]Itisstartedat300mg3timesdaily,andtitratedupto12001800mg/day.Thedrugisusuallywelltoleratedwithfew
sideeffects(sedation,irritability,ataxia,weightgain).
Topiramate
Topiramate(blockssodiumchannelsandpotentiatesGABAactivity)hasbeenshowntobeeffectiveinreducingET
(monotherapyoraddontherapy).[10],[11],[12]Itisstartedat2550mgatbedtimeandtitratedupto400mg/day.Side
effectsincludesuppressionofappetite,weightloss,andparesthesias.Furtherstudiesarerequiredtoproveitsefficacyin
ET.
Zonisamide
Zonisamide(actsonsodiumandcalciumchannels)hasbeenreportedtobeusefulinET,especiallyfortremorsofvoice,
face,tongue,andhead.[13]Itisinitiatedat25mgatbedtimeandgraduallyincreasedto200mg/day.Sideeffectsinclude
sleepiness,fatigue,headache,andparesthesias.ThedrugcanbeusedasmonotherapyoraddontherapyofETinthose
whohaveunsatisfactoryresponsetootherantitremormedicationsatmaximallytolerateddosage.Furtherstudiesare
requiredtodeterminetheefficacyofzonisamideinET.
Otherdrugs
Therearereportsofpossiblebeneficialeffectsofpregabalin(startingat50mg/dayandescalatedto600mg/day),
atenolol(50150mg/day),sotalol(75200mg/day),nadolol(120240mg/day),clozapine(675mg/day),andnimodipine
(120mg/day)inET.ClozapineisrecommendedonlyforrefractorycasesoflimbtremorinET[14],[15]andpatients
shouldbemonitoredforagranulocytosis.Furtherstudiesarerequiredtoprovetheefficacyofthesedrugs.
BotulinumToxin

InmedicallyrefractorycasesofET,injectionsofBotulinumToxinAinthetremorogenicmuscles(preferablyunder
electromyographicguidanceforselectingthemuscles)maybeuseful[4].Theinjectionhasbeenshowntobeusefulfor
limb,head,andvoicetremor.[16],[17],[18],[19],[20]Sideeffectsincludetemporaryweaknessoftheinjectedmusclesand
breathlessness,dysphagia,andhoarsenessfollowingtreatmentforvoicetremor.Botulinumtoxininjectionshouldbe
performedonlybyatrainedandexperiencedneurologist.
SurgicalTreatment

SurgicaltreatmentforETisreservedforthoseselectedpatientswhohaveseveretremornotadequatelycontrolledby
medicaltherapy.Contralateralthalamotomy(VIMnucleus)ordeepbrainstimulation(DBS)ofthethalamusarehighly
effectiveinreducingtremor.[21],[22]InIndia,thechoicebetweenthalamotomyandDBSisprimarilydictatedbythe
availabilityofexpertiseandthecostofDBS.Bilateralthalamotomyisnotrecommendedduetoitsadversesideeffects.
Therefore,inthosewhocannotaffordDBS,unilateralthalamotomycontralateraltothemostseverelyaffectedsideis
recommended.InpatientswhocanaffordDBS,bilateralDBSisrecommendedtosuppresstremorofbothsides.Thereis
contradictoryevidencethatbilateralDBSmaybeusefulforsuppressingheadandvoicetremor.Sideeffectsaremore
frequentwithbilateralDBS.
Insummary,ETisadisorder,whichcanleadtoasignificantmorbidityinsomepatients,especiallyfunctionaldisability.
Theapproachtomanagementshouldbeguidedbytheseverityoftremor,thepartsofthebodyinvolved,occupationof
thepatient,andphysicalandsocialdisability.

References
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FindleyLJ,KollerWC.Definitionsandbehavioralclassifications.In:FindleyLJ,KollerWC.editors.Handbook
ofTremorDisorders.NewYork,NY:MarcelDekker1995.p.15.

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GuidelinesformanagementofessentialtremorPalPKAnnIndianAcadNeurol

ChenJJ,SwopeDM.Essentialtremor.JPharmaPract200720:458.

KollerWC,BiaryN,ConeS.Disabilityinessentialtremor:Effectoftreatment.Neurology198636:10014.

ZesiewiczTA,ElbleR,LouisED,HauserRA,SullivanKL,DeweyRBJr,etal.PracticeParameter:Therapiesfor
essentialtremorReportoftheQualityStandardsSubcommitteeoftheAmericanAcademyofNeurology.
Neurology200564:200820.

KollerWC,VetereOverfieldB.Acuteandchroniceffectsofpropranololandprimidoneinessentialtremor.
Neurology198939:15878.

PapaSM,GershanikOS.Orthostatictremor:Anessentialtremorvariant.MovDisord19883:97108.

PahwaR,LyonsK,HubbleJP,BusenbarkK,RienerthJD,PahwaA,etal.Doubleblindcontrolledtrialof
gabapentininessentialtremor.MovDisord199813:4657.

GironellA,KulisevskyJ,BarbanojM,LpezVillegasD,HernndezG,PascualSedanoB.Arandomizedplacebo
controlledcomparativetrialofgabapentinandpropranololinessentialtremor.ArchNeurol199956:47580.

OndoW,HunterC,VuongKD,SchwartzK,JankovicJ.Gabapentinforessentialtremor:Amultipledose,
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ConnorGS.Adoubleblindplacebocontrolledtrialoftopiramtetreatmentforessentialtremor.Neurology
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OndoWG,JankovicJ,ConnorGS,PahwaR,ElbleR,StacyMA,etal.Topiramateinessentialtremor:Adouble
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FrimaN,GrunewaldRA.Adoubleblind,placebocontrolled,crossovertrialoftopiramateinessentialtremor.Clin
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MoritaS,MiwaH,KondoT.Effectofzonisamideonessentialtremor:Apilotcrossoverstudyincomparisonwith
arotinolol.ParkinsonismRelatDisord200511:1013.

CeravoloR,SalvettiS,PicciniP,LucettiC,GambacciniG,BonuccelliU.Acuteandchroniceffectsofclozapinein
essentialtremor.MovDisord199914:46872.

PakkenbergH,PakkenbergB.Clozapineinthetreatmentoftremor.ActaNeurolScand198673:2957.

BrinMF,LyonsKE,DoucetteJ,AdlerCH,CavinessJN,ComellaCL,etal.Arandomized,doublemasked,
controlledtrialofbotulinumtoxintypeAinessentialhandtremor.Neurology200156:15238.

PahwaR,BusenbarkK,SwansonHylandEF,DubinskyRM,HubbleJP,GrayC,etal.Botulinumtoxintreatment
ofessentialheadtremor.Neurology199545:8224.

WisselJ,MasuhrF,ScheloskyL.Quantitativeassessmentofbotulinumtoxintreatmentin43patientswithhead
tremor.MovDisord199712:7225.

WarrickP,DromeyC,IrishJC,DurkinL,PakiamA,LangA.Botulinumtoxinforessentialtremorofthevoice
withmultipleanatomicalsitesoftremor:Acrossoverdesignstudyofunilateralversusbilateralinjection.
Laryngoscope2000110:136674.

HertegardS,GranqvistS,LindestadPA.Botulinumtoxininjectionsforessentialvoicetremor.AnnOtolRhinol
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ZirhA,ReichSG,DoughertyPM,LenzFA.Stereotacticthalamotomyinthetreatmentofessentialtremorofthe
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PahwaR,LyonsKL,WilkinsonSB,CarpenterMA,TrsterAI,SearlJP,etal.Bilateralthalamicstimulationfor
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