抗精神病药mesolimbic中脑边缘皮层

Psychosis(fundamentalderangementofthemind,asinschizophrenia,characterizedbydefectiveorlostcontactwithrealityespeciallyasevidencedbydelusions,hallucinations,anddisorganizedspeechandbehavior)Mesolimbic-mesocorticalpathway(中脑边缘/皮层Palliative(reducepainwithoutremovingitsNeuroleptic(anyofthepowerfultranquilizers,asthephenothiazinesandbutyrophenones,usedespeciallytotreatpsychosisandbelievedtoactbyblockingdopaminenervousreceptors-calledalsoneuroleptic)Akathisia(uncontrollablerestlessness静坐不能Dystonia(abnormalmovementandmuscletone,张力障Tardivedyskinesia(迟发性运动障碍Neurolepticmalignantsyndrome(神经阻滞药恶性Enuresis(aninvoluntarydischargeofurine尿失禁Pathognomonic(distinctivelycharacteristicofaparticulardisease,特异病征性的)Wordsalad(ajumbleofextremelyincoherentspeechassometimesobservedinschizophrenia,言语杂乱)Perseveration(continuationofsomething,asrepetitionofaword,usuallytoanexceptionaldegreeorbeyondadesiredpoint,持续言语)Grandiose(plannedonalargescale夸大的Bizarre(strikinglyoutoftheordinaryasodd,extravagant,oreccentricinstyleormode)Chlorpromazine(氯丙嗪Perphenazine(奋乃静Thioridazine(硫利达嗪Thioxanthene(噻吨类Thiothixene(替沃噻吨Butyrophenones(丁酰苯类Clozapine(氯氮平Risperidone(利培酮Olanzapine(奥氮平Quetiapine(喹硫平Aripiprazole(阿立哌唑Lithium(锂

Fluoxetine(氟西汀Citalopram(西酞普兰Escitalopram(依他普仑Paroxetine(帕罗西丁Sertraline(舍曲林Fluvoxamine(氟伏沙明GeneralTherearemanydifferentcategoriesofmentaldisorders,themostimportanttypesare:PsychoticdisordersAffectivedisordersDepression,AnxietyGeneralDrugaAntimanicAnxiolytics(refertoSedative–hypnoticsCase A17-yearoldmalehighschoolstudentisreferredtothepsychiatryclinicforevaluationofsuspectedschizophrenia.Afteradiagnosisismade,Haloperidolisprescribedatagraduallyincreasingdose.Thedrugimproveshispositivesymptomsbutultimatelycausesintolerablesideeffects.Althoughmorecostly,Risperidoneisthenprescribed,whichoverthecourseofseveralweeksoftreatment,improveshissymptomsandistoleratedbythepatient.Inthetreatment,whatbenefitsdotheatypicalantipsychoticsofferoverthetraditionalagentssuchasInadditiontothemanagementofschizophrenia,whatotherclinicalindicationswarrantconsiderationoftheuseofdrugsnominallyclassifiedasantipsychotics?AchronicpsychiatricCharacterizedbysomeorallofthefollowings,presentforatleastonemonth:formalthoughtdisorder,delusions,hallucinations,disorderedbehavior,disorganizedspeech,negativesymptoms,anddeteriorationinwork,interpersonalrelations,andself-NosinglefeatureispathognomonicofPositive Thoughtdisorder:disorderofthenormalfunctionsofthinkingandformationofideas.Patientmaycomplainofthoughtsslowed,blocked,ortheirmindbeingempty.Inpatient’sspeech,theremaybetangentialorlooseassociations,wordsalad,orperseveration.Thoughtblockingmaybeevidentbypatientstoppinginmid- Delusions:falsebeliefthatcannotbecorrectedbyanappealtoreason,andwhichisinconsistentwiththepatient’sculturalbackground.Delusionsofpersecution(paranoiddelusions)arecommon.Delusionsmayalsobegrandiose(e.g.patientisanimportantpersonsuchasareligiousfigure),orsomatic(e.g.patient’sbrainhasbeenstolen).Feelingsofpassivityorthoughtinfluencearealsocommon.Positive Hallucinations:falseperceptionwithoutanobjectivestimulus(asdistinct,forexample,fromanillusion,whichisadistortionofreality).Auditoryhallucinationsarethemostcommon.Typically,voicesareheardtalkingaboutthepatientinthethirdperson.Hallucinationsmayalsobeolfactory,tactile,visual,orgustatory.Ifhallucinationsoftheseothersensorymodalitiesareprominent,amedicalcauseormedication/substanceinducedpsychoticdisordershouldberuledout. Bizarrebehavior:childlikeoraimlessbehaviors;agitationandimpulsivenessareunprovoked,sometimeswithburstsofaggression.Someabnormalbehaviormaybetheresultofhallucinations,e.g.voicescommandingthepatienttoact.Negative Socialdisorder:lossofpersonalabilitiessuchasinitiative,interest,andpleasureinlifeandotherpeople;emotionsmaybeblunted;thereispovertyofspeechanddiminishedactivityandself-care. Cognitivedisorder:memory,attention,andcomprehensiondefectsandalackofdecision-makingcapabilityarecommon,especiallyinolderpatients.PositiveSymptoms&thePossibleRolesofDopamine,Serotonin&GlutamateItisbelievedthatpositivesymptomsmayresultprimarilyfromabnormaldopamineoveractivationinthemesolimbicpathway.AllknowntherapeuticallyeffectiveantipsychoticdrugshavesomeaffinityforblockingD2dopaminergicDopamineThefirstneurotransmitter-basedconcepttobedevelopedbutisnolongerconsideredadequatetoexplainallaspectsofthedisease.Nevertheless,itisstillhighlyrelevanttounderstandthemajordimensionsofschizophrenia,suchaspositiveandnegativesymptoms,cognitiveimpairment,andpossiblydepression.Itisalsoessentialtounderstandthemechanismoftheactionofmostandprobablyallantipsychotics.erimportantdopaminergiclyn

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ynse(,,)ny2 ePositiveSymptoms&thePossibleRolesofDopamine,Serotonin&GlutamateAlthoughdopamineseemstoplayapredominantroleforthepositivesymptomsofschizophrenia,otherneurotransmittersmayalsobeinvolved,includingserotonin(5-HT),GABA&glutamate:thehallucinogensLSD&mescalineareknowntoproducetheirhallucinogeniceffectsbystimulatingserotonin(5-HT2A)receptorstheatypicalantipsychoticsblockbothD2and5-HT2Abothphencyclidineandketamine,whichcausebothcognitiveimpairment&psychosisexerttheseeffectsbyantagonizingglutamateNMDAreceptorsHencehaeiscouldbeinvolvedinesssitdNegativeSymptoms&DopaminergicHypofunction?exppshasbeensuggestedtocontributetothedesf varietyofotherneurotransmittersarelikelyinvolvedaswell,includingnorepinephrine,acetylcholine,serotonin,glutamate&histamine.Theoreticallyene,eesTopreventTotreattheacuteTorehabilitatetheTopreventToimprovequalityoflifeforpatientandTreatmentofschizophreniaisnotsolelybasedondecreasinghallucinationsanddelusions. Atypicalantipsychoticsarefirst-linetreatmentbecauseoftheirmorebenignadverseeffectprofileaswellastheirefficacyintreatingnegativesymptomscomparedtotypicalantipsychotics.Psychotherapyandsocialinterventionsareimportantpartsofacomprehensivetreatmentplan.Effectivetreatmentrequiresacombinationofmedication,psychotherapy,andappropriatepsychosocialmeasures.Antipsychoticmedicationsarethemainstayoftreatment: Atypicalantipsychoticsincluderisperidone,olanzapine,quetiapine,aripiprazole,etc..Allareusedasfirst-linetreatmentorwhenconventionalmedicationshaveprovedineffective,andallaresafeandeffectiveinbothacutephaseandmaintenance.Theygenerallyhaveawidertherapeuticspectrumthantypicalantipsychoticsandaremoreeffectiveagainstnegativesymptoms.Atypicalantipsychoticshaveareducedriskofextrapyramidaladverseeffectsandtardivedyskinesia. Typicalantipsychoticsincludechlorpromazine,haloperidol,andfluphenazine.Theyaresafeandeffectiveintreatingacutesymptomsandpreventingrelapse,buthavearelativelyhighriskofadverseeffectssuchastardivedyskinesiaandparkinsonism,especiallyinolderpatients.TheyaremainlyeffectiveagainstthepositiveTheatypicalantipsychoticclozapinecarriesariskofseizuresandagranulocytosisandisonlyrecommendedwhentypicalandotheratypicalantipsychoticshaveprovedineffective.Ifnoresponsetoacute-phasemedicationat4-6weeks,changeofmedicationshouldbeconsidered.Followingacutephase,medicationisusuallycontinuedatsamedoseforatleast6months.Dependingontheindividualcase,dosemaythenbegraduallyreducedover4-8weekstolevelofmaintenance.Becauseofhighriskofrelapse,maintenanceshouldcontinuefor1-2yearsaftertheinitialepisodeandatleast5yearsfollowingmultipleepisodes.Thereafter,reductionshouldbespreadoverseveralmonths,withfrequentassessmentsandreconsiderationofdiagnosisiftheyareabletobetitratedoffantipsychotics.Generally,patientswithschizophreniawillbetakingantipsychoticsfortherestoftheirlives.ClassificationofMaincategorieslPhenothiazines(chlorpromazine,thioridazine,etc.)Thioxanthenes(thiothixene)Butyrophenones(haloperidol)l(e.g.clozapine,risperidone,Antipsychoticdrugsblockat csas rReceptorRECEPTORDSEROTONRATDDPADADRENERG HD6F9P4---T--R21-H49O4QC09*N-DataareKivaluesdeterminedbycompetitionwithradioligandsforbindingtotheindicatedrecepto-Compoundsareinrank-orderofdopamineD2-receptorafin-D2/5-HT2AratioindicatesrelativepreferenceforD2vs.serotonin5-HT2AreceptoConventionalantipsychoticscanbeclassifiedashigh,intermediate,orlowpotency.High-potencyantipsychoticshaveahigheraffinityfordopaminereceptorsandlessforα-adrenergicandmuscarinicreceptors.Low-potencyantipsychotics,whicharerarelyused,havelessaffinityfordopaminereceptorsandrelativelymoreaffinityforα-adrenergic,muscarinic,andhistaminicreceptors.Phenothiazines(吩噻嗪类Chlorpromazine:wintermine(氯丙嗪，冬眠灵Drugclass:antipsychotic(typical,conventional,neuroleptic)&antiemetic.Antipsychoticshavebeenamainstayoftherapysincetheintroductionofchlorpromazineinthemid-1950s,whichrevolutionizedFirstsynthesizedonDecember11,1950,chlorpromazinewasthefirstdrugdevelopedwithspecificantipsychoticaction,andwouldserveastheprototypeforthephenothiazineclassofdrugs,whichlatergrewtocompriseseveralotheragents.TheintroductionofchlorpromazineintoclinicalusehasbeendescribedasthesingleGREATESTadvanceinpsychiatriccare,dramaticallyimprovingtheprognosisofpatientsinpsychiatrichospitalsworldwide.MechanismsofBlockadeofdopamine2receptors(D2)isresponsibleforreducingthepositivesignsofpsychosis&improvingotherbehaviors.ThecombinedeffecttoblockD2,histamineH1&muscarinicM1receptorsinthevomitingcenterispostulatedtoreducenausea&vomiting.Blocksα1&5-HT2>D2MultiplereceptortypesareblockedbymostantipsychoticdrugsduetoD2receptorsbelongingtoaReceptorSuperfamilythatshareahighdegreeofsequencePharmacologicCentralnervous Antipsychoticeffect---blockD2receptorsinmesolimbic-mesocorticalpathway; Antiemeticeffect---inhibitD2receptorsinchemoreceptortriggerzoneordirectlydepressthemedullarvomitingcenter; Temperature-regulatingeffect---inhibithypothalamicthermoregulationcenter.Pharmacologic Autonomicnervoussystem:blockac1and-hc,resultinhypotension,dry constipationandblurredvision. Endocrinesystem:blockD2receptorsinr prolactinanddecreasethereleaseofcorticotropin(促肾上腺皮质激素)andpituitarygrowthhormone.Therapeutic①Psychosis(schizophrenia,typicallyreduces,butdoesnoteliminatethepositivesymptomsinit)andmanicphaseofbipolardisorder.lackofefficacyintreatingnegative②Intractablehiccups,&nauseaandHypothermiaanesthesiaandartificialhibernation.(usedwithpethidine(哌替啶)andpromethazine(异丙嗪),toproducedeepsleep,lowerthetemperature). hAdverseD2receptorblockadeinstriatum:extrapyramidalsymptoms-Parkinsonian-likemotorsideeffects;SupersensitivityofD2receptors:tardivedyskinesia-developsafterprolongedtherapy(e.g.>1yr);D2receptorblockade:neurolepticmalignantD2receptorblockadeinmesocortical&mesolimbicpathways:worseningofnegative&cognitivesymptoms(neuroleptic-induceddeficitsyndrome);D2receptorblockadeinpituitary:galactorrhea,amenorrhea,infertility,impotence.dyrAdverseExtrapyramidalreactionsoccurringParkinson’sAkathisia(uncontrollablePrefertouseDiphenhydramine)withPrefertouseDiphenhydramine)withbothsedativeantihistamine&anticholinergiceffects.ParkinsonismcanbetreatedAnti-cholinergicdrugs(Trihexphenidyl苯海索)DApromotingdrugs(AmantadinekrAdverseTardivedyskinesia(TD):rugComprisesmainlyinvoluntarymovementsoffaceandtongue,butalsooftrunkandlimbs.ItmaybeassociatedwithenhancementofDAEarlyrecognitionisimportant,sinceadvancedcasesmaybedifficulttoreverse.–SwitchtoClozapine,theatypicalagentwiththeleastlikelihoodofcausingit.etdeAdverseNeurolepticmalignant Life-threateningdisorderoccurinpatientswhoareextremelysensitivetotheextrapyramidaleffectsofSymptomaremarkedmusclerigidity,highfever,alteredbloodpressureandpulse,etc.. Treatment:DAagonists(bromocriptine),musclerelaxants(diazepam).Adverse Antimuscarinic:sedation,blurredvision,tachycardia,drymouth,constipation,difficultyurinating;toxicdoses-confusionalstate.Antihistamine:sedation,weightα-blockade:orthostatichypotension,failureto Cardiactoxicity:TorsadedePointes,dose-dependentincreaseinincidenceofsuddendeath. Rarebutlife-threatening:agranulocytosis,aplasticanemia,thrombocytopenia,seizures.CouldusechlorpromazinetocontrolhighBP?Couldadrenalinebeusedinthehypotensioninducedbychlorpromazine?CNSdepression,bonemarrowdepression,hypotension,Parkinsonism,hepaticdysfunction,glaucomaDrugCancause“epi-reversal”(hypotensiveresponse)whenepinephrineisadministeredi.v.toapatienttakingAntacids(maydecreaseabsorptionofPropranolol(mayincreaseserumchlorpromazineorpropranolollevels)Thioridazine(硫利达嗪Mildantipsychotic,anti-anxietyandantidepressantAtlowandmediumdosesitrelievestensionandanxiety,andactsagainstmultiplesymptoms(e.g.agitation,depression,sleepdisturbances)ofnon-psychoticmentaldisorders;Athigherdoses,effectiveincontrollingthesymptomsofpsychoticdisorders.Lowerextrapyramidalsideeffects,andhighersedativeDuetoconcernsaboutcardiotoxicityandretinopathyathighdosesthisdrugisnotcommonlyprescribed,reservedforpatientswhohavefailedtorespondto,orhavecontraindicationsfor,morewidelyusedFluphenazine(氟奋乃静Itsmainuseisasalongactinginjectiongivenonceeverytwoorthreeweekstopeoplewithschizophreniawhosufferfrequentrelapsesofillness.errc)Itssideeffectprofileissimilartohaloperidol,withstrongerextrapyramidalsideeffects;whilewithlesseffectsofsedatingandThioxanthenes(硫杂蒽类Thiothixene(替沃噻吨ThiothixeneistheonlyfirstgenerationtypicalthioxantheneantipsychoticapprovedforuseintheUnitedStates.Effectiveinthemanagementofwithdrawn,apatheticschizophrenicpatients;otheraffectivesymptoms,e.g.anxiety.Lowerincidenceofextrapyramidalsideeffects.Thebutyrophenonestendtobemorepotentandtohavefewerautonomiceffectsbutgreaterextrapyramidaleffectsthanphenothiazines. Haloperidol(氟哌啶醇):isthemostwidelyusedtypicalantipsychoticdrugdespiteitshighlevelofSimilaruseswithHaloperidol(氟哌啶醇VerypotentD2blocker(blocksD2>D1=D4>alpha1>5-HT2receptors).r,clsdeeffectss..rcdeeffectsthanlow-potencyneuroleptics;lowercsdeeffects,almostwithosee.Haloperidolisoneofthemostwidelyused“typical”TreatmentofpsychosisItisalsosometimesprescribedforbipolardisorder(althoughnotapprovedforthisindicationbyFDA)(e.g.an“offlabel”use).CNSParkinson’sProlongedQT(HaloperidolalsoprolongstheSideSimilartochlorpromazine,butwithlessanticholinergic,antihistamine&autonomicsideeffects.Thusitproducesrelativelylesssedation,weightgain&orthostatichypotensioncomparedtochlorpromazine.PotentD2Blockade:haloperidolproducesthehighestlevelofEPSorextrapyramidalsymptomsofconventionaloratypicalantipsychotics&ahigherincidenceoftardivedyskinesia.BlockofD2receptorsinpituitary:galactorrhea,Rare:neurolepticmalignantsyndrome,seizures,increasedriskofdeathinelderlypatientswithdementia-relatedAtypicalAtypicalagentsdifferfromtypicalantipsychoticsinthattheyarelesslikelytocause:involuntarymovementdisorderandrelatedadverseeffects;however,riskofmetabolicsyndrome(excessabdominalfat,insulinresistance,dyslipidemia,andhypertension)isgreaterthanconventionalantipsychotics.AllantipsychoticsblockD2receptorstosomedegree,buttheaffinityvaryfromdrugtodrugandithasbeenhypothesizedthatitisthevaryinginaffinitiesthatcausesachangeineffectiveness.Clozapine(氯氮平Clozapine,thefirstatypicalanti-psychoticmedication,wasdiscoveredinthe1950s,andintroducedintoclinicalpracticeinthe1970s.Clozapinefelloutoffavorduetoconcernsoverdrug-inducedagranulocytosis.Withresearchindicatingitseffectiveness(theonlyone)intreatment-resistantschizophreniaandthedevelopmentofanadverseeventmonitoringsystem,clozapinereemergedasaviableantipsychoticagent.MechanismofReceptoraffinityprofile:D4&alpha1>5-HT2A>D2&D1receptors.AlsoblocksM&H1Higheraffinityto4dA,erayo2rSerotonin-DopamineSchizophreniatPsychotic&manicsymptomscanimprovewithin1Itisrecommendedtowait4-6weekstodetermineefficacy,butmaytakeupto16-20weekstoshowagoodresponse(esp.intreatmentresistantcases).RenalorliverHeartWBCSideSrr countbeforetreatment,weeklybloodcountsfor1st6monthsoftherapy,andbiweeklycountsformonths6-12,andmonthlythereafter).Hypersalivation(canbeIncreasedriskofseizures(dose-Weightgain(frequent&canbesignificantinQTcprolongation(allantipsychotics),drowsiness/sedation,dizziness/vertigo,headache,constipation,sweating,tremor,disturbedsleep,etc..Olanzapine(奥氮平MechanismofBlocksD2&5-HT2AAlsohasantagonisticeffectson5-HT2Creceptorsthatmaycontributetoefficacyforcognitive&affectiveReceptoraffinity:5-HT2>D1-D4&alpha-1receptors;alsoblocksM&H1receptors.Bipolardisorder(maintenanceoracuteagitation/Alsomarketedasacombinationformulationwithfluoxetine(symbyax®)fortreatment-resistantdepression&depressiveepisodesassociatedwithbipolardisorder.SideDrowsiness,flusyndrome,increasedsalivation,nausea,tardivedyskinesia,weightgain,hyperglycemia,QTcprolongation(allantipsychotics).Quetiapine(Seroquel喹硫平MechanismofBlocksH1>alpha1>M1,3>D2>5-Depression/mania/maintenancetreatmentforbipolarSidePerhaps“less”weightgainthanolanzapine&QTcprolongation(allRisperidone(利培酮MechanismofBlocksD2&5-HT2AAlsoblocksM,alpha1&H1PsychosisProlongedRenalorliverRisperidone(利培酮SideDose-dependentextrapyramidalWeightgain&riskofdiabetes&Dose-dependentAripiprazole(Abilify阿立哌唑MechanismofAuniquelttD2&5-HT1AReceptorbindingaffinityprofileis:D2=5-HT2A>D4>alpha1=D1Becauseitisapartialagonist,aripiprazolewillreducedopamineeffectsinareasofthebrainwithhighdopaminelevels,butcanalsoresultinanetincreaseinstimulationofdopaminereceptorsinareasthathavelowdopaminelevels.ThisdifferenceinactionmayproducedifferentfunctionalresultscomparingtodrugsthatarepureD2postsynapticreceptorantagonists.IttheoreticallycouldcauseareductioninpsychosisbydecreasingDAactivityinlimbicareas,whileimprovingnegativesymptomsandcognitiveimpairmentsinfrontalareasduetostimulationof5-HT&DAreceptors.Maintenancetherapyforbipolardisorder,adjunctivetreatmentofmajordepressivedisorder;Treatmentofirritabilityassociatedwithautisticdisorder&agitationassociatedwithschizophrenia.SideNausea,vomiting,Headache,dizziness,QTcprolongation(allLowerweightgainliabilitycomparedtomostotheratypicalDrugChoiceamongantipsychoticdrugsisbasedmainlyondifferencesinadverseeffectsandpossibledifferencesinefficacy.Oneshouldbefamiliarwithonememberofeachofthethreesubfamiliesofphenothiazines,amemberofthethioxantheneandbutyrophenonegroup,andallofthenewercompounds.SomerepresentativeantipsychoticGeneric,Manyadverseeffects,especiallySlightextrapyramidalsyndrome;800mg/dlimit;noparenteralform;Depotformalso(?)IncreasedtardiveParenteralformalsoavailable;(?)decreasedtardivedyskinesiaParenteralformalsoavailable;SevereextrapyramidalMaybenefittreatment-resistantpatients;littleextrapyramidaltoxicityMaycauseagranulocytosisinupto2%ofpatients;dose-relatedloweringofseizureBroadefficacy;littleornoextrapyramidalsystemdysfunctionatlowdosesExtrapyramidalsystemdysfunctionandhypotensionwithhigherdosesEffectiveagainstnegativeaswellaspositivesymptoms;littleornoextrapyramidalsystemWeightgain;dose-relatedloweringofseizurethresholdSimilartoolanzapine;perhapslessweightMayrequirehighdosesifthereishypotension;shortt1/2andtwice-daily Lowerweightgainliability,longhalf-novelmechanism

Uncertain,noveltoxicitiesAdversepharmacologiceffectsofantipsychoticAutonomicnervousLossofaccommodation,drymouth,difficultyurinating,MuscariniccholinoceptorOrthostatichypotension,impotence,failuretoejaculateAlpha-adrenoceptorParkinson'ssyndrome,akathisia,TardiveSupersensitivityofEndocrine乳综合征)infertility,blockaderesultingWeightPossilbecombinedH15-HT2Atappropriatedosages,antipsychotics(exceptclozapine&perhapsolanzapine)areofequalSomepatientswhofailtoonedrugmayrespondtoanother.So,severaldrugshavetobetriedtofindthemosteffectiveoneforthepatient.Patientswhohavebecomerefractorytotwoorthreeantipsychoticsgiveninsubstantialdosesbecomecandidatesforclozapineorhigh-doseolanzapine(30-50%effectively).DosageAntipsychoticdrugsareoftengivenindivideddailydoses,titratingtoaneffectivedosage.Thelowendofthedosagerangeinthetableshouldbetriedforatleastseveralweeks.Afteraneffectivedailydosagehasbeendefinedforanindividualpatient,dosescanbegivenlessOnce-dailydoses,usuallygivenatnight,arefeasibleformanypatientsduringchronicmaintenancetreatment.GeneralDrugAntipsychoticdrugs(anti-schizophrenicAnxiolytics(refertoSedative–hypnoticsBipolarBipolardisorderisamooddisordercharacterizedbyepisodesofmaniaorhypomaniaseparatedbyperiodsofdepressionorof‘normal’mood. Patientswithdepressioncandevelopmaniaorhypomanialaterinthecourseoftheillness;15%ofpatientswhohavedepressionarelikelytobebipolar,andthediagnosisisoftenmissed. Lithiumremainsthefirst-linetreatmentforbipolardisorder,buttherearemanyothermoodstabilizersthatmaybemoretolerable.Antidepressantsshouldgenerallynotbeusedwithoutamoodstabilizerinpatientswithknownmaniaorhypomania.Bipolardisorderisachronicconditionthatusuallyrequireslifelongcare,soagoodtherapeuticalliance,educationofpatientandfamily,andtheuseofpsychotherapymustallbeconsidered.AntimanicMood-stabilizer:LithiumCarbonateTreatmentofthemanicstageofbipolar–Lithiumissometimescombinedwithanantipsychotictotreatacutemanicepisodes. Afirstlinedrugformaintenancetreatmentofbipolardisorder–Lithiumpreventsorreducestheintensityofsubsequentepisodesofmaniainbipolarechns:themechanismsbywhichlithiumexertsitstherapeuticeffectsarenotentirelyclear:Alterscation(阳离子transportacrosscellmembraneinnerveandmusclecellsandinfluencesreuptakeofserotoninand/orInhibitstherecyclingofneuronalmembranephosphoinositides(PIP,磷酸肌醇)involvedingenerationofsecondmessengers.recyclingofinositol肌醇isinhibitedbyAdversePolyuria(withresultingNausea,vomitingandTremor,mild Variousneurologicaleffects,progressingfromconfusionandmotorimpairment,to,nd.Lithiumtoxicityiscloselyrelatedtoserumlithiumlevels,andcanoccuratdosesclosetotherapeuticlevels(verynarrowtherapeuticindex),requiringfrequentteststomonitorlithiumtroughplasmaEarlysymptomsoflithiumtoxicitycanusuallybetreatedbyreductionorcessationofdosageofthedrugandresumptionofthetreatmentatalowerdoseafter24to48hours.es Majordepressivedisorder(MDD)ischaracterizedbyapervasivesadmoodandthelossofpleasureinmostactivities.Itisachronicandrelapsingdiseaseassociatedwithsignificantdistressandimpairment.ItisimportanttodistinguishbipolardisorderfromMDD,asthetherapeuticapproachisThepatientshouldbeaskedaboutepisodesofmania,hypomaniaandfamilyhistoryofbipolardisorder.ThetreatmentmodalitiesforMDDaimtodothefollowing:Reduceandultimatelyremoveallsignsandsymptomsofthedepressivesyndrome. Relieveanydisordersinadditionto,orresultingfrom,thedepression,suchasmalnutritionandsubstance RestorethepsychosocialandoccupationalfunctionofthepatientpriortotheonsetofthedepressivePreventdiseaserelapseandThemostimportantaspectofchoosinganinitialorsubsequentmedicationforthetreatmentofMDDisthemanagementofthepatient’sacceptabilityortolerabilityofpotentialadverseeffects.AgoodrelationshipwiththecareproviderandaclearunderstandingofthenatureofMDDanditstreatmentcanincreaseTricyclicantidepressantsTCAs,三环类):Selective5-HTreuptakeinhibitors SelectiveSerotonin–NorepinephrineInhibitors(SNRIs):Monoamineoxidaseinhibitors:Phenelzine,Asthefirst-lineantidepressants,whicharesecond-generationantidepressants,amongwhichtherearenodifferencesinefficacy,thechoicetouseselectiveserotoninreuptakeinhibitors(SSRIs)(eg,citalopram,fluoxetine,sertraline);serotonin-norepinephrinereuptakeinhibitors(SNRIs)(eg,duloxetine,venlafaxine);orothersecond-generationantidepressantmedications,likebupropionormirtazapinewilldependonindividualpatientfactors.Coexistingdiseaseandotherriskfactors,tolerabilityandpriorresponse,andcosttopatientareallimportantconsiderations.Tricyclicantidepressants(TCAs)andmonoamineoxidaseinhibitors(MAOIs)aresecond-linetherapiesforMDD.Theselectiveserotoninreuptakeinhibitors(SSRIs),themostcommonclinicallyusedagents,areaclassofantidepressantsconsideredthecurrentstandardofdrugtreatment.ThepopularityofSSRIsstemslargelyfromtheireaseofuse,safetyinoverdose,relativetolerability,andbroadspectrumofuses.FluoxetineCitalopramParoxetineSertralineEscitalopramFluvoxamineMechanismsof neinWithieesoncentralnorepinephrineanddopaminefunction.reesbecauseofminimalbindingtocholinergic,histaminic,andα-adrenergicreceptors.TherapeuticTreatmentofdepressionandbipolaraffectiveAnxietydisorder,obsessive-compulsivedisorder,eatingdisorder.AdverseNausea,anorexiaduetoincreaseserotonergicactivityinthegutwhichemergeearlyandtendtoimproveafterthe1stweek.CNSstimulation,nervousness,headache,andinsomnia,seizureswhenoverdose.Serotoninsyndromeisapotentiallylife-threateningadversedrugreactionduetoexcessserotonergicactivityatCNS(hyperpyrexia,convulsions,andcoma)whencombinedusagewithMAOinhibitorsDiminishedsexualfunctionandinterest;weightInteractionwithMAOIs,TCAs,SerotoninManifestationscanbegroupedintothefollowingMentalstatusalterations:Anxiety,agitationandAutonomichyperactivity:Tachycardia,hypertension,hyperthermia,shivering,vomiting,diarrheaNeuromuscularhyperactivity:Tremor,musclehypertoniaorrigidity,myoclonus,hyperreflexiaAllserotonergicdrugsshouldbeInseverecases,hyperthermiaistreatedbycooling.Neuromuscularblockadewithappropriatesedation,muscleparalysis,andothersupportivemeasuresmaybenecessary.Ifsymptomspersistdespitesupportivemeasures,theserotoninantagonistcyproheptadine(赛庚啶)canbegiven.Citalopram(西酞普兰Escitalopram(依他普仑Citalopramisaracemic(