Depressionandanxiety

Louhaiyan（婁海燕）InstituteofPharmacologySchoolofMedicineShandongUniversitylouhaiyan@1Depression

Commonpsychiatricdisease,11%

WHO，Depressionwillbecomethemainkillertopeoplein21thcenturyBLUEFLU2Depressionisanillnessthatischaracterizedbyaseriesofchangesthatgraduallycausesignificantimpairmentoftheactivityofpeopleconcerned.Itismorethanfeelingblue,downinthedumpsorsadaboutaparticularissueorsituation.Itisamedicalconditionthatrequiresdiagnosisandtreatment3SymptomsofDepressionFIVEORMOREOFTHEFOLLOWINGFORATLEASTTWOWEEKS:Feelingsofsadness,depressedmoodand/orirritabilityLossofinterestorpleasureinactivitiesChangesinweightorappetiteChangesinsleeppattern-notenoughortoomuch4SymptomsofDepressionFeelingsofguilt,hopelessnessorworthlessnessInabilitytoconcentrate,rememberthingsormakedecisionsConstantfatigueorlossofenergyRestlessnessordecreasedactivityRecurrentthoughtsofsuicideordeath5人很煩？愛發脾氣或對你的親友漠不關心？6Hamiltonratingscalefordepression（漢密爾頓抑郁量表)7EpidemiologyThemostcommonpsychiatricdisorderDepressionincidenceMen:13%Women:21%Bipolardisorder:1.3-1.8%Ageofonset:25-35yearMajorriskfactor:stress8EtiologyBiologicalfactorsSocialfactorsPsychologicalfactors9BiologicalfactorsGeneticHighprevalenceinfirstdegreerelativesHighconcordancewithmonozygotictwinsShortalleleofserotonintransportedgene,2003Medicalillness:Parkinson's,Alzheimer's,cancer,diabetesorstrokeVascularchangesinthebrainChronicorseverepainPrevioushistoryofdepressionSubstanceabuse10SocialfactorsLoneliness,isolationRecentbereavementLackofasupportivesocialnetwork11PsychologicalfactorsTraumaticexperiencesDamagetobodyimageFearofdeathFrustrationwithmemorylossRoletransitions12NeurobiologyofdepressionThemonoaminedeficiencytheoryDecreasedlevelsoractivityof

nor-epinephrineand/orserotoninAbnormalityinHPAaxisHippocampusvolume↓13TreatmentforDepressionApproximately80%ofpeoplewhoreceivetreatmentforDepressionimprove.Therearethreetypesoftreatment:PsychotherapyMedicationElectroconvulsiveTherapy(ECT,電休克治療)14

Tricyclic

antidepressants(TCAs)Monoamineoxidase

inhibitors(MAOIs)

Norepinephrinereuptakeinhibitors(NARIs)

Selectiveserotoninreuptakeinhibitors(SSRIs)Serotoninandnorepinephrinereuptake

inhibitors(SNRIs)Antidepressantdrugs15丙米嗪（imipramine）氯米帕明（clomipramine

）阿米替林（amitriptyline）多塞平（doxepin）三環類：Ⅰ.Tricyclicantidepressants(TCA)161.CNS：

produceinhibitiononnormalperson,

elevatingthemoodthatisdepressed

slowonset:2-3wImipramine

(丙米嗪，米帕明）Mechanisms：

blocktheuptakeofNAand5-HT

【Pharmacologicaleffectsandmechanism】172.autonomicnervoussystem

blockM-R3.cardiovascularsystemhypotension:blockα1–Rarrhythmias,tachycardia:NA↑quinidine-likeinhibitoryactiononheart

usedwithcautioninpatientswithcardiovasculardisease【Pharmacologicaleffectsandmechanism】18【Clinicaluses】

1.depressionscausedbyallkindsofreasons2.enuresis(遺尿癥)inchildren3.anxietyandphobia(恐怖癥)【Adversereactions】1.atropine-likeaction2.cardiovascularreaction

19三環類抗抑郁藥的作用及機制抑制突觸前膜對5-HT和NA的重攝取阻斷M-R阻斷

1-R阻斷H1-R奎尼丁樣心肌抑制作用抗抑郁心律失?？诟伞⒁暳δ：⒈忝?、尿潴留血壓過度鎮靜心肌內NA突觸間隙5-HT和NA20doxepin（多塞平，多慮平）

抗焦慮作用強，對伴有焦慮癥狀的抑郁癥療效最佳。

21Ⅱ

Monoamineoxidase

inhibitors(MAOIs)

：異煙肼（isoniazid）異卡波肼（isocarboxazid）嗎氯貝胺（moclobemide）Adversereaction:hypertensivecrisis,liverinjury22【Pharmacologicaleffectsandmechanism】

InhibitMAO,andreducethedegradationofmonoamine.【Clincaluses】:atypicaldepressionnotfirstchoice【Adversereactions】

Severe:hypertensioncrisis

23

Ⅲ

NAreuptakeinhibitorsDesipramine(地昔帕明)Maprotiline(馬普替林)Nortriptyline(去甲替林)TCASelectivelyreducereuptakeofNAWeaksedationandanticholinergicactivityOnsetrapid24ⅣSelective5-HTreuptakeinhibitors(SSRIs)Fluoxetine(Prozac,氟西汀,百憂解)Paroxetine(Paxil,帕羅西汀,賽洛特)Sertraline(Zoloft,舍曲林,郁樂復)Fluvoxamine(Luvox,氟伏沙明,蘭釋)Citalopram(Celexa,西酞普蘭,喜普妙)Firstline25氟西汀（fluoxetine,百憂解）

selectivelyinhibit5-HTreuptakenoaffinitytothereceptorsinCNSand

periphery，lessadversereactionsbettertoleranceandsecuritythanTCAstakeeffectsafter2-6weeksusedfordepression,compulsion(強迫癥)

polyphagia(貪食癥)26Ⅴ5-HTandNAreuptakeinhibitors(SNRIs)

Venlafaxine(文拉法辛,怡諾思）

Duloxetine(度洛西?。〩aveadvantagesoverSSRIsFasteronsetofaction(<2weeks)Usedfordepressionandanxiety27ElectroconvulsiveTherapy(ECT)Second-linetreatmentFasteractingthanmostmedicationsIsusedinlifethreateningsituationstoachievefastreliefCanbeusedincombinationwithmedicationSideeffects:short-termmemoryloss28Section2

Anti-manicDrugs29BipolarDisorder(Manic-depressivedisorder)Peoplewiththistypeofillnesschangebackandforthbetweenperiodsofdepressionandperiodsofmania(anextremehigh).Symptomsofmaniamayinclude:LessneedforsleepOverconfidenceRacingthoughtsRecklessbehavior(行為魯莽）Increasedenergy30repeatedepisodesofmaniaordepression,alternatingmaniaanddepressionMechanisms:

5-HT↓NA↑mania5-HT↓NA↓depressionManic-depressivedisorder(躁狂抑郁癥)

—bipolaraffectivedisorder31Antimanicdrug(modestabilizingagents)LithiumcarbonateAntipsychoticagents(氯丙嗪、氟哌啶醇、氯氮平、利培酮)Antiepilepticagents(卡馬西平、丙戊酸鈉)Calciumblockers(維拉帕米)32

Lithiumcarbonate(碳酸鋰)

—“Mood-stabilizing”agent【Pharmacologicaleffectsandmechanism】

littleimpactonnormalperson,anti-mania,sometimesalsoeffectivefordepression33碳酸鋰的可能作用機制1.抑制腦內神經末梢對NA、DA的釋放突觸間隙單胺類遞質減少2.促進NA、DA的重攝取及滅活3.抑制AC及PLC介導的反應4.影響Na+、Ca2+、Mg2+

轉運影響神經功能34【Clinicaluses】manic-depressivepsychosisespeciallyforacuteandmildmania(80%)

35Lithiumtoxicity

therapeuticconcentration:0.8-1.5mmol/Ltoxicconcentration:>2mmol/L

monitorblooddrugconcentration,withdrawalat1.6mmol/L【Adversereactions】

36nausea,vomit,abdominalpain,profusediarrhea,andataxia,mentalconfusion,hyper-reflexia,tremor,convulsionIntoxicationcanbeusuallyreversedbyosmoticdiuresisorbydialysis(透析)37Section3

Anti-anxietyDrugs38AnxietyAnxietyisanunpleasante