三叉神经痛卡马西平.docx
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三叉神经痛卡马西平.docx
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三叉神经痛卡马西平
Classicaltrigeminalneuralgia(CTN)isasevereneuropathicpaininthedistributionofoneormorebranchesofthetrigeminalnerve,whichoccursinrecurrentepisodes,causingdeteriorationinqualityoflife,affectingeverydayhabitsandinducingseveredisability.TheaimofthisreviewistogiveanoverviewofthecurrentliteratureonpharmaceuticaltreatmentoptionsforCTNintheelderly.Thefirst-linetreatmentforthemanagementofCTNinadultsisanantiepileptic—carbamazepineoroxcarbazepine.Thereisalackofresearchontheuseofantiepilepticsintheelderly.Thisisadeficiency,astheuseofantiepilepticsraisesanumberofproblemsduetothepolypharmacotherapycommoninolderpatients.Thiscaninducedruginteractionsduetoco-morbiditiesandchangesinpharmacokineticsandpharmacodynamics.Furthermore,thesideeffectsofcarbamazepineincludecentralnervoussystemdisturbances,suchasalackofbalance,dizziness,somnolence,renaldysfunctionandcardiacarrhythmias,whicharepoorlytoleratedbytheelderly.Unfortunately,theefficacyandsafetyofalternativetreatmentoptionshavenotbeensystematicallyevaluated.Onthebasisofthecurrentliterature,itisnotpossibletogiveanevidence-basedrecommendationforfirst-linepharmaceuticalmanagementofCTNspecificallyfortheelderly.
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DrugsAging.2015;32(9):
717–726.
Publishedonline2015Sep4. doi:
10.1007/s40266-015-0293-6
PMCID:
PMC4579266
PharmaceuticalManagementofTrigeminalNeuralgiaintheElderly
M.A.E.-M.Oomens
and T.Forouzanfar
Authorinformation ► CopyrightandLicenseinformation ►
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Abstract
Classicaltrigeminalneuralgia(CTN)isasevereneuropathicpaininthedistributionofoneormorebranchesofthetrigeminalnerve,whichoccursinrecurrentepisodes,causingdeteriorationinqualityoflife,affectingeverydayhabitsandinducingseveredisability.TheaimofthisreviewistogiveanoverviewofthecurrentliteratureonpharmaceuticaltreatmentoptionsforCTNintheelderly.Thefirst-linetreatmentforthemanagementofCTNinadultsisanantiepileptic—carbamazepineoroxcarbazepine.Thereisalackofresearchontheuseofantiepilepticsintheelderly.Thisisadeficiency,astheuseofantiepilepticsraisesanumberofproblemsduetothepolypharmacotherapycommoninolderpatients.Thiscaninducedruginteractionsduetoco-morbiditiesandchangesinpharmacokineticsandpharmacodynamics.Furthermore,thesideeffectsofcarbamazepineincludecentralnervoussystemdisturbances,suchasalackofbalance,dizziness,somnolence,renaldysfunctionandcardiacarrhythmias,whicharepoorlytoleratedbytheelderly.Unfortunately,theefficacyandsafetyofalternativetreatmentoptionshavenotbeensystematicallyevaluated.Onthebasisofthecurrentliterature,itisnotpossibletogiveanevidence-basedrecommendationforfirst-linepharmaceuticalmanagementofCTNspecificallyfortheelderly.
Classicaltrigeminalneuralgia(CTN)isasevereneuropathicpaininthedistributionofoneormorebranchesofthetrigeminalnerve,whichoccursinrecurrentepisodes,causingdeteriorationinqualityoflife,affectingeverydayhabitsandinducingseveredisability.TheaimofthisreviewistogiveanoverviewofthecurrentliteratureonpharmaceuticaltreatmentoptionsforCTNintheelderly.Thefirst-linetreatmentforthemanagementofCTNinadultsisanantiepileptic—carbamazepineoroxcarbazepine.Thereisalackofresearchontheuseofantiepilepticsintheelderly.Thisisadeficiency,astheuseofantiepilepticsraisesanumberofproblemsduetothepolypharmacotherapycommoninolderpatients.Thiscaninducedruginteractionsduetoco-morbiditiesandchangesinpharmacokineticsandpharmacodynamics.Furthermore,thesideeffectsofcarbamazepineincludecentralnervoussystemdisturbances,suchasalackofbalance,dizziness,somnolence,renaldysfunctionandcardiacarrhythmias,whicharepoorlytoleratedbytheelderly.Unfortunately,theefficacyandsafetyofalternativetreatmentoptionshavenotbeensystematicallyevaluated.Onthebasisofthecurrentliterature,itisnotpossibletogiveanevidence-basedrecommendationforfirst-linepharmaceuticalmanagementofCTNspecificallyfortheelderly.
KeyPoints
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Introduction
Intheprimarycaresector,diagnosisandinitialmanagementoforofacialpainareoftenperformedbyfamilydoctorsanddentists[1].Trigeminalneuralgia(TN)isaspecificdiagnosisbasedonclinicalfindings,athoroughclinicalhistoryandanexamination[2].Amultidisciplinaryteamshouldmanagepatientswithcomplicatedfacialpain[1].AccordingtotheInternationalclassificationofheadachedisorders,thirdedition(ICHD-3),TNisdefinedasadisordercharacterizedbyrecurrent,unilateral,brief,electricshock-likepains,abruptinonsetandtermination,limitedtothedistributionofoneormoredivisionsofthetrigeminalnerveandtriggeredbyinnocuousstimuli[3].TheannualoverallincidenceofTNrangesfrom12.6/100,000to27/100,000peopleperyear,withanincreaseintheincidencewithadvancingage[4].ThemechanismofTNisdescribedashyperexcitabilityoftrigeminalrootfibresneartheentryzoneintotheponsbecauseofmechanicalcompression(vascularortumorous)orinflammatorydemyelination(multiplesclerosis).EmpiricalevidencehasindicatedthatvascularcompressionofthetrigeminalnerverootisassociatedwithTNinabout95 %ofpatients[5].Magneticresonanceimaging(MRI)studieshavegivenmoreinsightsintothepathogenesisofTN.TrigeminalnervemicrostructureabnormalitiescanbeidentifiedwithnewMRItechniquestogetherwithtrigeminaltractography.DemyelinationwithoutsignificantaxonalinjuryseemstobeanimportantfactorinthepathogenesisofTN.Furthermore,thereseemstobeastateofmaintainedsensitizationoftrigeminalnociceptivesystemsinthebrain.AntiepilepticdrugsarethoughttoworkinthetreatmentofTNbyblockingvoltage-sensitivesodiumchannels,makingbraincellslessexcitable[6].Also,grey-mattervolumereductionhasbeenfoundintheprimaryandsecondarysomatosensorycorticesofTNpatients[4, 7].
TNcanbedividedintosymptomaticTN(STN)andclassical(idiopathic)TN(CTN)[3].STNcanbeclassifiedbycausativeorcontributingfactors,asproposedbyElleret al.[8]—forexample,trigeminalneuropathicpainresultingfrommultiplesclerosisplaquesortumours.Unfortunately,mostTNisidiopathic,andtheaetiologyisnotclear.
TheguidelinesonpharmaceuticalTNmanagementpublishedbytheAmericanAcademyofNeurology(AAN)andtheEuropeanFederationofNeurologicalSocieties(EFNS)recommendcarbamazepine(CBZ;200–1200 mg/day)oroxcarbazepine(OXC;600–1800 mg/day)asfirst-linetherapy[9].PatientsunresponsivetoCBZorOXCshouldbereferredforadd-ontherapywithlamotrigineorsurgery.Elderlypatients(definedaspersonsaged60yearsorolder)oftenpresentwithanumberofco-morbidandage-relatedconditions,whichoftenrequirepolypharmacy.Antiepilepticshavewell-knowninteractionswithotherdrugs.Therefore,itisachallengetoestablishamedicaltreatmentforCTNintheelderlywithoutinducingchangesinpharmacodynamicsandpharmacokinetics,andwithoutcausingsafetyproblems.
TheaimofthisreviewistogiveanoverviewofthecurrentlyavailableliteratureonthepharmaceuticalmanagementofCTNpatients,withafocusontheelderly.
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MaterialsandMethods
InclusionandExclusionCriteria
Thestudiesincludedinthisreviewwerealldouble-blind,randomized,controlledtrials(RCTs)involvingnon-surgicaltreatmentofCTN.ThereviewexcludedarticlesonSTN,articlesnotavailableinEnglishandnon-RCTstudydesigns.
OutcomeMeasures
Painrelief,definedasdecreasedfrequencyanddecreasedintensityofpainfulparoxysms,wasregardedastheprimaryoutcome.Secondaryoutcomemeasuresweresideeffects.
LiteratureSearches
Toidentifyeligiblestudies,Medline,EmbaseandClinicaltrials.govweresearchedwiththeMeSHterm‘trigeminalneuralgia’.ThesearchwasrestrictedtoRCTs,clinicaltrialsandEnglish-languagearticles.
DataCollectionandAnalysis
Thetitlesandabstractsofthearticleswerescreened,andthetwoauthorsofthereview(MOandTF)decidedwhicharticleswereeligibleforinclusion.Informationonthenumbersofparticipants,lengthoffollow-upandoutcomemeasureswasextractedfromeacharticle,usingadataextractionform.
AssessmentofRisksofBias
Therisksofbiasineachtrialwereassessedbyscoringthesecurityofrandomization,allocationconcealment,comparabilityofgroupsatbaseline,doubleblindingandhandlingofdropouts.Incasesofuncertainty,theauthorsoftherelevantarticlewerecontactedwheneverpossible.
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Results
LiteratureSearches
Theliteraturesearchresultedin171relevantstudies.Afterreviewoftheabstracts,18articlesinvolvingnon-surgicaltreatmentofCTNwereidentified.Ofthese,sixarticlesassessedantiepilepticdrugsand12investigatednon-antiepilepticdrugs(Fig. 1).
Fig. 1
Flowchartofarticleselection. i.n. intranasalapplication, m. mucosalapplication, s.c. subcutaneousapplication
StudyDescriptions
AnoverviewofallincludedstudiesisgiveninTable 1.ThefourstudiesinvestigatingtheeffectivenessofCBZ,allpublishedbefore1970,showedthatCBZreducedboththefrequencyandtheintensityofpainfulparoxysmsin76 %ofincludedpatients[10–13].Atotalof165patientswereincluded[meanage58 years(range34–84)],andtherewasameanfollow-upof23months(range1–46).CBZdosagesrangedfrom100to2400 mg/day.Sideeffectsofdrowsiness,constipation,vertigo,nauseaandvomiting,andarashweredescribed.
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