12/28/2015 BipolarAffectiveDisorderMedication:Anxiolytics,Benzodiazepines,Moodstabilizers,Anticonvulsants,Antipsychotics,2ndGeneration,Antipsych

BipolarAffectiveDisorderMedication
Author:StephenSoreff,MDChiefEditor:IqbalAhmed,MBBS,FRCPsych(UK)more...

Updated:Oct26,2015

MedicationSummary
Appropriatemedicationformanagingbipolaraffectivedisorder,ormanicdepressiveillness(MDI),dependsonthe
stagethepatientisexperiencing.Thechoiceofagentdependsonthepresenceofsymptomssuchaspsychotic
symptoms,agitation,aggression,andsleepdisturbance.Drugcategoriesincludemoodstabilizers,anticonvulsants,
andantipsychotics

Anxiolytics,Benzodiazepines
ClassSummary
Bybindingtospecificreceptorsites,benzodiazepinesappeartopotentiatetheeffectsofgammaaminobutyricacid
(GABA)andfacilitateinhibitoryGABAneurotransmissionandtheactionofotherinhibitorytransmitters.

Viewfulldruginformation

Lorazepam(Ativan)

Lorazepamisananxiolytichypnoticwithanintermediateonsetofeffectsandarelativelyintermediatehalflife.By
increasingtheactionofGABA,whichisamajorinhibitoryneurotransmitterinthebrain,itmaydepressalllevelsof
thecentralnervoussystem(CNS),includingthelimbicandreticularformation.

Viewfulldruginformation

Clonazepam(Klonopin)

ClonazepamisalongactingbenzodiazepinethatincreasespresynapticGABAinhibitionandreducesmonosynaptic
andpolysynapticreflexes.ItsuppressesmusclecontractionsbyfacilitatinginhibitoryGABAneurotransmissionand
otherinhibitorytransmitters.

Moodstabilizers
ClassSummary

Lithiumisthedrugcommonlyusedforprophylaxisandtreatmentofmanicepisodes.A2012studysuggestedthat
lithiummayalsohaveaneuroprotectiverole. [81]However,thisagentisalsoassociatedwithanincreasedriskof
reducedurinaryconcentratingability,hypothyroidism,hyperparathyroidism,andweightgain.Theconsistentfinding
ofahighprevalenceofhyperparathyroidismshouldpromptphysicianstocheckpatientcalciumconcentrations
beforeandduringtreatment.

Lithiumisnotassociatedwithasignificantreductioninrenalfunctioninmostpatients,andtheriskofendstage
renalfailureislow. [84]Lithiumtherapymayservetoprotectandpreservethehippocampalvolumes,incontrastto
patientswithmajordepression(ie,unipolar),whoshowdiminishedhippocampalvolumes. [85]

Furthermore,recognizingthatpatientswithbipolaraffectivedisorderareatriskforsuicide,lithiummayalsohave
someantisuicidalaction.AreportfromLewitkaandBauersuggestthatlithiummaybeanoptionforpatientswith
affectivedisorderswhoareatriskforsuicide.However,theycautionthatlithiumisstillamedicationthatrequires
carefulassessmentandmonitoring.Patientadherenceisessential. [43]Manyfemalepatientswithbipolardisorder
willdiscontinuetheirlithiummedicationwhentheybecomepregnant. [115]

Viewfulldruginformation

Lithiumcarbonate(Lithobid)

Lithiumisconsideredafirstlineagentforlongtermprophylaxisinbipolarillness,especiallyforclassicbipolar
disorderwitheuphoricmania.Italsocanbeusedtotreatacutemania,althoughitcannotbetitrateduptoan
effectivelevelasquicklyasvalproatecan.Evidencesuggeststhatlithium,unlikeanyothermoodstabilizer,may
haveaspecificantisuicideeffect.

Monitoringbloodlevelsiscriticalwiththismedication.Serumlevelsshouldbedeterminedtwiceweeklyduringthe
acutephase,anduntiltheserumlevelandclinicalconditionofthepatienthasbeenstabilized.

Anticonvulsants
ClassSummary

Anticonvulsantshavebeeneffectiveinpreventingmoodswingsassociatedwithbipolardisorder,especiallyinthose
patientsknownasrapidcyclers.Forthedepressedphase,moodstabilizers,suchaslithiumandlamotrigine,are
preferred,becauseantidepressantsmaypropelapatientintoamanicepisodeorexacerbateirritabilityinmixed
symptommania.Gabapentin,althoughnotamoodstabilizer,alsomayhaveanxiolyticproperties.Themostwidely
usedanticonvulsantshavebeencarbamazepine,valproate,andlamotrigine.Morerecently,topiramateand
oxcarbazepinealsoarebeingtried.

NotethattheDepartmentofVeteransAffairs/DepartmentofDefense(VA/DoD)donotrecommendlamotrigine,
topiramate,andgabapentininpatientswithmaniaormixedepisodes. [3]

Viewfulldruginformation

Carbamazepine(Equetro)

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Carbamazepineiseffectiveinpatientswhohavenothadaclinicalresponsetolithiumtherapyandwhohaverapid
cyclingbipolardisorder.Itsefficacyisnotwellestablishedforlongtermusetherefore,periodicallyreevaluatethe
longtermrisksandbenefitsofcarbamazepineforindividualpatients.Thisdrugcanalsoacttoinhibitseizures
inducedthroughthekindlingeffect,whichisthoughttooccurbywayofrepeatedlimbicstimulation.

Viewfulldruginformation

Valproatesodium,valproicacid,divalproexsodium(Depakene,Depakote,DepakoteER,
Depacon,Stavzor)

Valproatehasproveneffectivenessintreatingandpreventingmania.Itisclassifiedasamoodstabilizerandcanbe
usedaloneorincombinationwithlithium.Thisagentisusefulintreatingpatientswithrapidcyclingbipolardisorders
andhasbeenusedtotreataggressiveorbehavioraldisorders.Acombinationofvalproicacidandvalproatehas
beeneffectiveintreatingpersonsinmanicphase,withasuccessrateof49%.

Viewfulldruginformation

Lamotrigine(Lamictal,LamictalODT,LamictalXR)

Lamotrigineisananticonvulsantthatappearstobeeffectiveinthetreatmentofthedepressedphaseinbipolar
disorders.ItisusedforthemaintenancetreatmentofbipolarIdisordertodelaythetimetooccurrenceofmood
episodes(depression,mania,hypomania,mixedepisodes)inadultstreatedforacutemoodepisodeswithstandard
therapy.

Viewfulldruginformation

Topiramate(Topamax)

Topiramatehasanofflabelindicationforthetreatmentofbipolardisease.Inasmallretrospectivereview,marked
improvementoccurredin62%ofpatientswhentopiramatewasaddedtotheircurrentregimen. [115]Itisunclearif
topiramate'sefficacyoccursonlyasadjunctivetreatment.Morestudiesareneededtoexaminepotentialbenefitsof
thisdrugintreatingbipolar.Unlikeconventionalneuroleptics,topiramateisnotassociatedwithweightgain.

Antipsychotics,2ndGeneration
ClassSummary

Secondgeneration,oratypical,antipsychoticsareincreasinglybeingusedfortreatmentofbothacutemaniaand
moodstabilizationinpatientswithbipolarIdisease.

Viewfulldruginformation

Asenapine(Saphris)

Asenapineisindicatedasmonotherapyfortheacutetreatmentofmanicormixedepisodesthatareassociatedwith
bipolarIdisorder.Itisalsoindicatedasadjunctivetherapywithlithiumorvalproatefortheacutetreatmentofmanic
ormixedepisodesassociatedwithbipolarIdisease.Theefficacyofasenapineisthoughttobemediatedthrougha
combinationofantagonistactivityatdopamine2andserotonin(5HT2)receptors.

Viewfulldruginformation

Ziprasidone(Geodon)

Ziprasidoneisapprovedforthetreatmentofacuteormixedepisodesthatareassociatedwithbipolardisorder.It
canbeusedasmaintenancetreatmentorasanadjuncttolithiumorvalproate.

Viewfulldruginformation

Quetiapine(Seroquel,SeroquelXR)

Quetiapineisindicatedforacutetreatmentofmanic(immediatereleaseandextendedrelease[XR])ormixed(XR)
episodesthatareassociatedwithbipolarIdisorder.Itcanbeusedasmonotherapyoradjunctivelywithagentssuch
aslithiumordivalproex.

Viewfulldruginformation

Risperidone(Risperdal,RisperdalConsta,RisperdalMTab)

RisperidoneisindicatedforshorttermtreatmentofacutemanicormixedepisodesthatareassociatedwithbipolarI
disorder.Itcanbeusedaloneorincombinationwithlithiumorvalproate.Risperidonecanbeusedinadultsand
adolescentsaged1017yearswithbipolarIdisorder.

Viewfulldruginformation

Aripiprazole(Abilify,AbilifyDiscmelt)

Aripiprazoleisindicatedfortheacuteandmaintenancetreatmentofmanicormixedepisodesassociatedwith
bipolarIdisorder.Itcanbeusedaloneorincombinationwithlithiumorvalproate.

Viewfulldruginformation

Olanzapine(Zyprexa,ZyprexaZydis)

OlanzapineisusedfortheacuteandmaintenancetreatmentofmanicormixedepisodesassociatedwithbipolarI
disorder.Itcanbeusedaloneorincombinationwithlithiumorvalproate.Olanzapinecanbeusedinadultsand
adolescentsaged1317yearswithbipolarIdisorder.

Viewfulldruginformation

Olanzapineandfluoxetine(Symbyax)

Thedrugcombinationincludesolanzapine,asecondgenerationantipsychotic,andfluoxetine,aselectiveserotonin
reuptakeinhibitor.ThisdrugisindicatedfortheacutetreatmentofdepressiveepisodesassociatedwithbipolarI
disorderinadults.Theclinicaleffectsofthisagenthavenotbeenstudiedinpatientsyoungerthan18years.

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Viewfulldruginformation

Clozapine(Clozaril,FazaCloODT)

Clozapinehasanofflabelindicationfortreatmentofacutemanicepisodesassociatedwithbipolardisorderand
treatmentofrefractorybipolarmania.ThisagentdemonstratesweakD2receptorandD1receptorblockingactivity.
Clozapinealsoactsasanantagonistatadrenergic,cholinergic,histaminergic,andserotonergicreceptors.

Viewfulldruginformation

Paliperidone(Invega)

Paliperidonemaybeusedforrefractory,moderatetoseveremaniaaloneorincombinationwithlithiumor
valproate.Thisagentistypicallyreservedforpatientswhodeclineelectroconvulsivetherapy(ECT)andwhodonot
respondtomedicationcombinationsinvolvinglithiumorvalproateplusaripiprazole,haloperidol,oranotherfirst
generationantipsychotic.

Viewfulldruginformation

Cariprazine(Vraylar)

Precisemechanismbywhichcariprazineworksforbipolardisorderisunknown.Efficacycouldbemediatedthrough
acombinationofpartialagonistactivityatcentraldopamine(D2)andserotonin5HT1Areceptors.Itisindicatedfor
manicormixedepisodesassociatedwithbipolar1disorder.

Antipsychotics,1stGeneration
ClassSummary

Firstgenerationantipsychotics,alsoknownasconventionalortypicalantipsychotics,areefficaciousfortreatingboth
psychoticandnonpsychoticmanicandmixedepisodes,aswellashypomania.Theseagentsarestrongdopamine
D2antagonists.However,eachdruginthisclasshasvariouseffectsonotherreceptors,suchas5HT2serotonin,
alpha1,histaminic,andmuscarinicreceptors.

Viewfulldruginformation

Loxapineinhaled(Adasuve)

Themechanismofactionforloxapineisunknown,butitistheorizedtoantagonizecentraldopamineD2and
serotonin5HT2areceptors.Theinhaleddosageformisindicatedforacutetreatmentofagitationassociatedwith
schizophreniaorbipolarIdisorderinadults.

Viewfulldruginformation

Haloperidol(Haldol)

Haloperidolisusedfortheacutetreatmentofmaniaormixedepisodesinpatientswithbipolardisorder.Itcanbe
usedaloneorincombinationwithlithiumorvalproateinanadultpatient.Haloperidolblockspostsynapticdopamine
receptors(D2)inthemesolimbicsystemandincreasesdopamineturnoverbyblockadeoftheD2somatodendritic
autoreceptor

Antipsychotics,Phenothiazine
ClassSummary

Phenothiazineantipsychotics,whichareclassifiedasfirstgenerationantipsychotics,areefficaciousfortreatingboth
psychoticandnonpsychoticmanicandmixedepisodes,aswellashypomania.

Viewfulldruginformation

Chlorpromazine(Thorazine)

ChlorpromazineisusedtotreatmanicandmixedepisodesinpatientswithbipolarIdisorder.Itcanbeusedalone
orincombinationwithlithiumorvalproate.Chlorpromazineblockspostsynapticdopaminereceptors(D2)inthe
mesolimbicsystemandincreasesdopamineturnoverbyblockadeoftheD2somatodendriticautoreceptor

AntiparkinsonAgents,DopamineAgonists
ClassSummary

DopamineagonistsarenonergotagentsthatbindtoD2andD3dopaminereceptorsinthestriatumandsubstantia
nigra.

Viewfulldruginformation

Pramipexole(Mirapex,MirapexER)

Pramipexoleisusedasaddontherapyforpatientswhoseconditionisrefractorytocombinationtherapyandhave
bipolardepression.Pramipexoleisanonergot,fulldopamineagonistthatbindstoD2andD3dopaminereceptors.

ContributorInformationandDisclosures
Author
StephenSoreff,MDPresidentofEducationInitiatives,Nottingham,NHFaculty,BostonUniversity,Boston,MA
andDanielWebsterCollege,Nashua,NH

StephenSoreff,MDisamemberofthefollowingmedicalsocieties:ACMHA:TheCollegeforBehavioralHealth
Leadership

Disclosure:Nothingtodisclose.

Coauthor(s)

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12/28/2015 BipolarAffectiveDisorderMedication:Anxiolytics,Benzodiazepines,Moodstabilizers,Anticonvulsants,Antipsychotics,2ndGeneration,Antipsych
LynneAlisonMcInnes,MD,MSAssociateClinicalProfessorofPsychiatry,UniversityofCalifornia,San
Francisco,SchoolofMedicine

LynneAlisonMcInnes,MD,MSisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,American
PsychiatricAssociation,AmericanSocietyofHumanGenetics

Disclosure:Nothingtodisclose.

ChiefEditor
IqbalAhmed,MBBS,FRCPsych(UK)Faculty,DepartmentofPsychiatry,TriplerArmyMedicalCenterClinical
ProfessorofPsychiatry,UniformedServicesUniversityoftheHealthSciencesClinicalProfessorofPsychiatry,
ClinicalProfessorofGeriatricMedicine,UniversityofHawaii,JohnABurnsSchoolofMedicine

IqbalAhmed,MBBS,FRCPsych(UK)isamemberofthefollowingmedicalsocieties:Academyof
PsychosomaticMedicine,AmericanNeuropsychiatricAssociation,AmericanSocietyofClinical
Psychopharmacology,RoyalCollegeofPsychiatrists,AmericanAssociationforGeriatricPsychiatry,American
PsychiatricAssociation

Disclosure:Nothingtodisclose.

Acknowledgements
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference

Disclosure:MedscapeSalaryEmployment

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