chapter 6 antipsychotic drugs

Chapter 6Chapter 6

Antipsychotic drugsAntipsychotic drugs

Jining Medical CollegeJining Medical College

School of Mental Health School of Mental Health

Zhai JinguoZhai Jinguo

Main PointsMain Points

GraspGrasp ：： Therapeutic indications Therapeutic indications of of antipsychoticsantipsychotics

Common side effects and treatmentCommon side effects and treatment

Clinical treatment methods Clinical treatment methods

FamilarFamilar ：： The pharmacological effects of different The pharmacological effects of different

antipsychoticsantipsychotics

Understand Understand ：： ClassificationClassification of of antipsychoticsantipsychotics

Classification of psychopharmacaClassification of psychopharmaca

AntipsychoticsAntipsychotics AntidepressantsAntidepressants Antimanic drugs (Mood Antimanic drugs (Mood

stabilizers)stabilizers) Antianxiety drugs (anxiolytics)Antianxiety drugs (anxiolytics) Psychostimulants Psychostimulants Hypnotics Hypnotics Nootropic drugsNootropic drugs

New WordsNew Words Antipsychotic drugs/agents Antipsychotic drugs/agents

Antipsychotics Antipsychotics 抗精神病药抗精神病药 neuroleptics neuroleptics 神经阻滞剂神经阻滞剂 Typical antipsychotics Typical antipsychotics 典型抗精神病药典型抗精神病药 Atypical antipsychotics Atypical antipsychotics 非典型抗精神病药非典型抗精神病药 Potency Potency 效价效价 Extrapyramidal syndrome(EPS) Extrapyramidal syndrome(EPS) 锥体外系反应锥体外系反应 Hyperprolactinemia Hyperprolactinemia 高催乳素血症高催乳素血症 Acute dystonia Acute dystonia 急性肌张力障碍急性肌张力障碍 Akathisia Akathisia 静坐不能静坐不能 Parkinsonism Parkinsonism 类帕金森症类帕金森症 Tardive dyskinesia (TD) Tardive dyskinesia (TD) 迟发性运动障碍迟发性运动障碍 Neuroleptic Malignant Syndrome(NMS)Neuroleptic Malignant Syndrome(NMS) 恶性综合征恶性综合征

New WordsNew Words

Chlorpromazine Chlorpromazine 氯丙嗪氯丙嗪 Haloperidol Haloperidol 氟哌啶氟哌啶

醇醇 Perphenazine Perphenazine 奋乃静奋乃静 Thioridazine Thioridazine 硫利达硫利达

嗪嗪 Sulpiride Sulpiride 舒必利舒必利

Clozapine Clozapine 氯氮平氯氮平 Risperidone Risperidone 利培酮利培酮 Olanzapine Olanzapine 奥氮平奥氮平 Quetiapine Quetiapine 喹硫平喹硫平 Ziprasidone Ziprasidone 齐拉西酮齐拉西酮 Aripiprazole Aripiprazole 阿立派唑阿立派唑

Sertindole Sertindole 舍吲哚舍吲哚 Perospirone Perospirone 哌罗匹隆哌罗匹隆

New WordsNew Words

psychopathology psychopathology hallucination hallucination delusion delusion apathy apathy withdrawal withdrawal schizophrenia schizophrenia bipolar disorder bipolar disorder Pharmacodynamics Pharmacodynamics 药效动力学药效动力学 PharmacokineticsPharmacokinetics 药代动力学药代动力学

New WordsNew Words

dopamine dopamine dopaminergic dopaminergic serotonin serotonin SerotonergicSerotonergic muscarinemuscarine 毒蕈碱毒蕈碱 muscarinicmuscarinic 毒蕈碱的毒蕈碱的 epinephrineepinephrine 肾上腺素肾上腺素 / adrenaline / adrenaline adrenergicadrenergic 肾上腺素能的肾上腺素能的 norepinephrinenorepinephrine 去甲肾上腺素去甲肾上腺素 histaminehistamine 组胺组胺 histaminergichistaminergic 组胺能的组胺能的 antagonistantagonist agonistagonist enzymeenzyme

New WordsNew Words

Phenothiazines Phenothiazines 酚噻嗪类 Chlorpromazine Chlorpromazine benzamides benzamides 苯酰胺类 sulpiridesulpiride butyrophenones butyrophenones 丁酰苯类 haloperidol haloperidol dibenzoxazepines dibenzoxazepines 二苯氧氮平类 (loxapine)(loxapine) dihydroindolonesdihydroindolones 二氢吲哚酮类 (molindone )(molindone ) diphenylbutylpiperidines diphenylbutylpiperidines 二苯丁基哌啶类

(pimozide) (pimozide)

DefinitionDefinition

Antipsychotics are mainly given to control symptoms Antipsychotics are mainly given to control symptoms

of schizophrenia and other kinds of psychosis.of schizophrenia and other kinds of psychosis.

抗精神病药（抗精神病药（ antipsychotic drugsantipsychotic drugs ）主要用于治疗精神）主要用于治疗精神分裂症和其他具有精神病性症状的精神障碍。这类药物，分裂症和其他具有精神病性症状的精神障碍。这类药物，在通常治疗剂量时，不影响意识和智能，能有效地控制精在通常治疗剂量时，不影响意识和智能，能有效地控制精神病患者的精神运动性兴奋、幻觉妄想、敌对情绪、思维神病患者的精神运动性兴奋、幻觉妄想、敌对情绪、思维障碍和奇特行为等精神症状。除此之外，尤其新一代药物障碍和奇特行为等精神症状。除此之外，尤其新一代药物还可以改善动力低下和社会退缩等精神分裂症的阴性症状。还可以改善动力低下和社会退缩等精神分裂症的阴性症状。

History of antipsychoticsHistory of antipsychotics

History of antipsychoticsHistory of antipsychotics

2020 世纪世纪 5050 年代初年代初 : Chlorpromazine: Chlorpromazine

Rhone-Poulenc-SpeciaRhone-Poulenc-Specia 实验室实验室 FranceFrance

1958:1958: 保罗保罗 ·· 杨森杨森 Haloperidol Haloperidol

19581958 瑞士瑞士 clozapineclozapine ，， 19721972 年在瑞士和奥地利上市年在瑞士和奥地利上市 2020 世纪世纪 7070 年代年代 :sulpiride:sulpiride

2020 世纪世纪 9090 年代年代 ::RisperidoneRisperidone ，， QuetiapineQuetiapine ，， ZiprasidoZiprasido

nene

20022002 年年 1111 月月 FDAFDA 批准批准 aripiprazolearipiprazole

History of antipsychotics in AmericaHistory of antipsychotics in America

齐拉西酮齐拉西酮

1950 1960 1970 1980 1990 2000 2002

电休克等电休克等

氯丙嗪氯丙嗪氟奋乃静氟奋乃静

甲硫达嗪甲硫达嗪氟哌啶醇氟哌啶醇

氯氮平氯氮平利培酮利培酮

奥氮平奥氮平喹硫平喹硫平阿立哌阿立哌

唑唑

氯氮平氯氮平

The Classification of Antipsychotic DrugsThe Classification of Antipsychotic Drugs

Antipsychotic drugs have been classified into Antipsychotic drugs have been classified into typical typical

or first-generation antipsychoticsor first-generation antipsychotics and and atypical or atypical or

Second-generation antipsychoticsSecond-generation antipsychotics..

Typical antipsychotic drugs are those which produce Typical antipsychotic drugs are those which produce

extrapyramidal side-effects at clinically effective doses extrapyramidal side-effects at clinically effective doses

in the majority of patients. in the majority of patients.

Atypical antipsychotic drugs are those with a Atypical antipsychotic drugs are those with a

significantly lower propensity to produce significantly lower propensity to produce

extrapyramidal side-effects at clinically effective doses. extrapyramidal side-effects at clinically effective doses.

ClassificationClassification by Pharmacological effectsby Pharmacological effects

NameNameFirst-generation antipsychoticsFirst-generation antipsychotics

Typical antipsychotics Typical antipsychotics

NeurolepticsNeuroleptics

Second-generation antipsychoticsSecond-generation antipsychotics

Atypical antipsychotics Atypical antipsychotics

New antipsychoticsNew antipsychotics

MechanMechanismism

Block D2 receptorBlock D2 receptor Block D2 and 5-HT receptorBlock D2 and 5-HT receptor

DrugDrug

Chlorpromazine Chlorpromazine

Haloperidol Haloperidol

Perphenazine Perphenazine

SulpirideSulpiride

ClozapineClozapine

Risperidone Risperidone

Olanzapine Olanzapine

Quetiapine Quetiapine

Ziprasidone Ziprasidone

Aripiprazole Aripiprazole

EfficacyEfficacy efficacy with efficacy with positivepositive symptom symptomefficacy with efficacy with positivepositive and negative and negative

symptomsymptom

Side Side effectseffects moremore lessless

AntipsychoticsAntipsychotics EPS/TDEPS/TD ProlactinProlactin EffectEffect

First-generation First-generation antipsychoticsantipsychotics((HaloperidolHaloperidol))

Severe Severe EPS/TDEPS/TD

IncreaseIncreaseefficacy with efficacy with positivepositive

symptomsymptom

Second-generation Second-generation antipsychoticsantipsychotics(Risperidone (Risperidone

Ziprasidone )Ziprasidone )

Dose related Dose related

EPS EPS ／／ TDTDIncreaseIncrease

efficacy with efficacy with positivepositive and negative symptomand negative symptom

Third-generation Third-generation antipsychoticsantipsychotics(Clozapine (Clozapine

Olanzapine Olanzapine

Quetiapine Quetiapine ))

Less EPS/TDLess EPS/TD // Broad-spectrum effectBroad-spectrum effect

Maguire G. Journal of Clinical Psychiatry. 2002. 63 (Suppl 4): 56-62.

New ClassificationNew Classification of Antipsychoticsof Antipsychotics

H1M1

D2

1

conventional antipsychotic drug

First-generation antipsychoticsFirst-generation antipsychotics

pure D2 blocker

Stahl S M, Essential Psychopharmacology (2000)

5HT2A

D2

Second-generation antipsychoticsSecond-generation antipsychotics

SDASDA

5HT7

5HT6

5HT3

5HT2C

5HT1A

M1 H11

D1

D3D4

5HT2A

D2

clozapine

Multi-acting receptor targeted agentsMulti-acting receptor targeted agents

5HT6

5HT3

5HT2C

M1 H11

D1

D3D4

5HT2A

D2

olanzapine



5HT7

5HT6

H11

25HT2A

D2

quetiapine



Classification of typical antipsychotic drugs Classification of typical antipsychotic drugs according to potencyaccording to potency

Low-potency agentsLow-potency agents are those in which the usual dose are those in which the usual dose range in schizophrenia is equal to or greater than 200 range in schizophrenia is equal to or greater than 200 mg/day. mg/day.

e.g. chlorpromazine, sulpiridee.g. chlorpromazine, sulpiride 镇静作用强、抗胆碱能作用明显、对心血管和肝脏毒性较大、锥体外镇静作用强、抗胆碱能作用明显、对心血管和肝脏毒性较大、锥体外系副作用较小、治疗剂量较大。系副作用较小、治疗剂量较大。 High-potency agentsHigh-potency agents are those in which the dose range is are those in which the dose range is

between 2 and 120 mg/day . between 2 and 120 mg/day .

e.g. haloperidol, perphenazine e.g. haloperidol, perphenazine

镇静作用较弱、对心血管和肝脏毒性小、锥体外系副作用较大、治疗镇静作用较弱、对心血管和肝脏毒性小、锥体外系副作用较大、治疗剂量较小。剂量较小。

ClassificationClassification by chemical structureby chemical structure

ClassificationClassification DrugDrug Dosage Dosage rangerange

吩噻嗪类吩噻嗪类（（ phenothiazinephenothiaziness ））

氯丙嗪氯丙嗪（（ chlorpromazinchlorpromazinee ）） 200-600 mg/d200-600 mg/d

奋乃静奋乃静（（ perphenazineperphenazine ）） 10-60 mg/d10-60 mg/d

氟奋乃静氟奋乃静（（ fluphenazinefluphenazine ）） 10-40 mg/d10-40 mg/d

氟奋乃静葵酸酯氟奋乃静葵酸酯（（ FDFD ）） 12.5-50mg/212.5-50mg/2 周周硫杂蒽类硫杂蒽类（（ thioxanthenethioxanthene

ss ））氟哌噻吨氟哌噻吨（（ chlorprothixenchlorprothixen

ee ）） 2-12 mg/d2-12 mg/d

丁酰苯类丁酰苯类（（ butyrophenonebutyrophenoness ））

氟哌啶醇氟哌啶醇（（ haloperidolhaloperidol ）） 6-20 mg/d6-20 mg/d

氟哌啶醇葵酸酯氟哌啶醇葵酸酯（（ HDHD ）） 50-100mg/450-100mg/4 周周

五氟利多五氟利多（（ penfluridolpenfluridol ）） 20-60mg/20-60mg/ 周周苯甲酰胺类苯甲酰胺类（（ benzamidebenzamide

ss ））舒必利舒必利（（ sulpiridesulpiride ）） 200-1500mg/d200-1500mg/d

二苯二氮卓类二苯二氮卓类（（ dibenzodiazepinesdibenzodiazepines ））

氯氮平氯氮平（（ clozapineclozapine ）） 100-500mg/d100-500mg/d

奥氮平奥氮平（（ olanzapineolanzapine ）） 5-20mg/d5-20mg/d

喹的平喹的平（（ quetiapinequetiapine ）） 150-750mg/d150-750mg/d

苯丙异恶唑类苯丙异恶唑类（（ benzisoxazolebenzisoxazole ））利培酮利培酮（（ risperidonerisperidone ）） 2-6mg/d2-6mg/d

吩噻嗪类吩噻嗪类

硫杂蒽类硫杂蒽类

丁酰苯类丁酰苯类

苯甲酰胺类苯甲酰胺类

二苯二氮卓类二苯二氮卓类

According to pharmacological actionAccording to pharmacological action

Serotonin-dopamine antagonists, SDAs: Risperidone, Serotonin-dopamine antagonists, SDAs: Risperidone,

ziprasidone, sertindoleziprasidone, sertindole

Multi-acting receptor targeted agents: Multi-acting receptor targeted agents:

MARTAsMARTAs ，， clozapine, olanzapine, quetiapine, clozapine, olanzapine, quetiapine,

zotepinezotepine

Selective Selective D2/DD2/D ３３ receptors antagnists: amisulpridereceptors antagnists: amisulpride ，，

remoxiprideremoxipride

D2D2 、、 5-HT1A5-HT1A 受体部分激动剂和受体部分激动剂和 5-HT2A5-HT2A 受体拮抗剂受体拮抗剂 : :

aripiprazolearipiprazole

PharmacodynamicsPharmacodynamics 药效动力学药效动力学

PharmacokineticsPharmacokinetics 药代动力学药代动力学

Pharmacological mechanism of antipsychoticsPharmacological mechanism of antipsychotics

DA DA receptor blocker rolereceptor blocker role

5-HT receptor blocker role5-HT receptor blocker role

1 1 receptor blocker rolereceptor blocker role

M1 cholinergic receptor blocker roleM1 cholinergic receptor blocker role

H1 histamine receptor blocker roleH1 histamine receptor blocker role

Theraputic effects

Side effects

H1M1

D2

1

First-generation First-generation antipsychoticsantipsychotics

11-7 Stahl S M, Essential Psychopharmacology (2000)

5HT2A

D2

Second-generation Second-generation antipsychoticsantipsychotics

5HT75HT6

5HT3

5HT2C

5HT1A

M1 H11

2

D1

D3D4

5HT2A

D2

clozapine

multi-acting receptor targeted agentsmulti-acting receptor targeted agents ，， MARTAsMARTAs

5HT6

5HT3

5HT2C

M1 H11

D1

D3D4

5HT2A

D2

olanzapine

5HT7

5HT6

H11

25HT2A

D2

quetiapine

11-41 Stahl S M, Essential Psychopharmacology (2000)

BINDING PROFILE OF ANTIPSYCHOTICS

CLOZAPINEOLANZAPINE HALOPERIDOL RISPERIDONE

H121Musc5HT2C5HT2AD4D2

SERTINDOLE SEROQUEL ZIPRASIDONE ZOTEPINE

DATA FROM BYMASTER ET AL., 1996 & SCHOTTE ET AL., 1996

D1

Fig. 1.

hypothalamus

d

c

Nucleus accumbens

Tegmentum

bSubstantia nigra

Basal Ganglia

a

Dopamine Pathways

大脑的多巴胺能递质系统大脑的多巴胺能递质系统

中脑边缘通路

基底核

结节漏斗通路

被盖

区

黑质

中脑皮质通路

黑质纹状体通路

下丘脑

Dopamine Pathways

a. Nigrostriatal Pathway （黑质 - 纹状体通路） : EPS

b. Mesolimbic Pathway （中脑 - 边缘通路）：阳性症状

c. Mesocortical Pathway （中脑 - 皮层通路）：阴性症状

心境症状

认知症状

d. Tubero Infundibular Pathway （结节 - 漏斗通路）：催乳素

J Clin Psych 1998(16) (monograph)

EPS


Nigrostriatal pathway（黑质 - 纹状体通路）

Blockade of receptors in the nigrostriatal dopamine pathway causes them to up-regulate

This up-regulation may lead to tardive dyskinesia


mesolimbic overactivity = positive symptoms of psychosis

Mesolimbic Pathway（中脑 - 边缘通路）


primary dopamine deficiency

D2 receptor blockade

secondary dopamine deficiency

Mesocortical

Pathway （中脑 - 皮层通路

）increase in negative symptoms


Prolactin levels rise

Tuberoinfundibular pathway（结节 - 漏斗通路）

5-HT receptor blocker role5-HT receptor blocker role

黑质纹状体通路– 促进多巴胺释放

非典型抗精神病药物是5-HT2A 受

体的拮抗剂

预防 EPS

改善

抑郁

症状改善认知

保留抗精神病

作用

中脑皮质通路– 促进多巴胺释放

中脑边缘通路– 多巴胺释放不

受影响

constipation

LAXATIVE

blurred vision

dry mouth drowsiness


M1 INSERTED

H1 INSERTED


drowsiness

weight gain

drowsiness

decreased blood pressure

dizziness


1 INSERTED

BINDING PROFILE OF ANTIPSYCHOTICS

CLOZAPINEOLANZAPINE HALOPERIDOL RISPERIDONE

H121Musc5HT2C5HT2AD4D2

SERTINDOLE SEROQUEL ZIPRASIDONE ZOTEPINE

DATA FROM BYMASTER ET AL., 1996 & SCHOTTE ET AL., 1996

D1

Fig. 1.

抗精神病药物的受体结合及临床作用抗精神病药物的受体结合及临床作用

药物药物 DD22 5-HT5-HT22 αα11 αα22 HH11 MM11

氟哌啶醇氟哌啶醇 ++++++++ ++ ++++

氯氮平氯氮平 ++++ ++++++ ++++++ ++++++ ++++++++ ++++++++++

奥氮平奥氮平 ++++++ ++++++++ ++++ ++++++++ ++++++++

利培酮利培酮 ++++++ ++++++ ++++ ++++

思瑞康思瑞康 ++++ ++++ ++++++ ++++++

齐哌西酮齐哌西酮 ++++++++ ++++++++ ++++ ++

临床作用临床作用

减轻阳性减轻阳性症症状，状， EPSEPS ，，催乳素升催乳素升高高

减轻阴减轻阴性症状，性症状，缓解缓解EPSEPS

低血压，低血压，眩晕，反眩晕，反射性心动射性心动过速过速

抗抑郁抗抑郁镇静镇静体重增加体重增加

记忆损害记忆损害抗胆碱作抗胆碱作用缓解用缓解EPSEPS

Adapted from: Richelson e. J Clin Psychiatry 1996; 57(suppl 11): 4-11. Pickar D. Lancet 1995; 345:557-562Adapted from: Richelson e. J Clin Psychiatry 1996; 57(suppl 11): 4-11. Pickar D. Lancet 1995; 345:557-562

Therapeutical effect of antipsychoticsTherapeutical effect of antipsychotics

Antipsychotic actionAntipsychotic action Positive symptomsPositive symptoms

Negative symptomsNegative symptoms

Cognitive symptomsCognitive symptoms

Affective symptomsAffective symptoms

Non-specific sedation Non-specific sedation Prevent recurrence and relapsePrevent recurrence and relapse

Therapeutic Indications Therapeutic Indications of of AntipsychoticsAntipsychotics

Therapeutic Indications Therapeutic Indications of of AntipsychoticsAntipsychotics

Schizophrenia and Schizoaffective DisorderSchizophrenia and Schizoaffective Disorder ManiaMania Depression with Psychotic SymptomsDepression with Psychotic Symptoms Delusional DisorderDelusional Disorder Severe Agitation and Violent BehaviorSevere Agitation and Violent Behavior Borderline Personality DisorderBorderline Personality Disorder Substance-Induced Psychotic DisorderSubstance-Induced Psychotic Disorder Behavioral Disturbances in the ElderlyBehavioral Disturbances in the Elderly Mental Disorders Due to a Medical ConditionMental Disorders Due to a Medical Condition Tourette's DisorderTourette's Disorder Other IndicationsOther Indications

Schizophrenia and Schizoaffective DisorderSchizophrenia and Schizoaffective Disorder

Nearly all acute episodes of schizophrenia and Nearly all acute episodes of schizophrenia and

schizoaffective disorder, including first episode schizoaffective disorder, including first episode

psychosis and recurrence in chronic psychosis and recurrence in chronic

schizophrenia, should be treated with schizophrenia, should be treated with

antipsychotic medications.antipsychotic medications.

The psychiatrist should evaluate the patient's The psychiatrist should evaluate the patient's

mental status and physical condition before mental status and physical condition before

establishing a baseline for the administration of establishing a baseline for the administration of

antipsychotic medications. antipsychotic medications.

ManiaMania

Antipsychotic drugs are effective in reducing Antipsychotic drugs are effective in reducing excitement and psychotic symptoms in mania. excitement and psychotic symptoms in mania. These agents tend to have a more rapid onset of These agents tend to have a more rapid onset of action than antimanic drugs including lithium, action than antimanic drugs including lithium, valproic acid and carbamazepine. valproic acid and carbamazepine.

This observation has led to the widespread This observation has led to the widespread practice of using combined treatment with practice of using combined treatment with antipsychotic and antimanic drugs during the antipsychotic and antimanic drugs during the first days of treatment of severe excited states, first days of treatment of severe excited states, before the antimanic compound has its onset of before the antimanic compound has its onset of action. action.

ManiaMania

When the antimanic compound has become When the antimanic compound has become

effective, the dosage of antipsychotic can usually be effective, the dosage of antipsychotic can usually be

reduced or use of the drug can be discontinued. reduced or use of the drug can be discontinued.

Five SGAs—aripiprazole, olanzapine, quetiapine, Five SGAs—aripiprazole, olanzapine, quetiapine,

risperidone, and ziprasidone—are FDA-approved for risperidone, and ziprasidone—are FDA-approved for

acute mania. acute mania.

Depression with Psychotic SymptomsDepression with Psychotic Symptoms

Clear psychotic symptoms, such as delusions or Clear psychotic symptoms, such as delusions or

hallucinations, are observed in approximately hallucinations, are observed in approximately

25% of patients with major depressive disorder. 25% of patients with major depressive disorder.

These symptoms often respond poorly to These symptoms often respond poorly to

antidepressants when they are administered antidepressants when they are administered

alone, and usually require the use of adjunctive alone, and usually require the use of adjunctive

antipsychotic agents. antipsychotic agents.

ContraindicationContraindication

Severe disease of heart, liver, kidneySevere disease of heart, liver, kidney Severe general infectionSevere general infection Hypothyroidism Hypothyroidism （甲状腺功能低下）、（甲状腺功能低下）、 hypocorticism (hypocorticism ( 肾肾

上腺皮质功能减退上腺皮质功能减退 )) 、、 angle-closure glaucomaangle-closure glaucoma （闭角型青（闭角型青光眼）、光眼）、 drug allergydrug allergy （药物过敏）、（药物过敏）、 myasthenia gravismyasthenia gravis（重症肌无力）（重症肌无力）

Cautious : Hypoleucocytosis Cautious : Hypoleucocytosis （白细胞减少）、（白细胞减少）、 OldOld 、、 ChildChild

Pregnant and lactation womenPregnant and lactation women

Drug ChoiceDrug Choice

Target syndromeTarget syndrome Drug featureDrug feature History History Therapeutical effect and adverse effectTherapeutical effect and adverse effect Experience of doctorExperience of doctor IIndividual condition ndividual condition ：： age, physical and health age, physical and health

condition condition Economic condition Economic condition Compliance Compliance

● Once a diagnosis was made, to treat with Once a diagnosis was made, to treat with antipsychotics immediatelyantipsychotics immediately

● Simple drugSimple drug● Individualization Individualization ● Titrate from low doses, adjust titrate speed , Titrate from low doses, adjust titrate speed ,

choose treatment place according to severitychoose treatment place according to severity● Full dosage and full course Full dosage and full course ● To evaluate effect and side effect periodic and To evaluate effect and side effect periodic and

adjust treatment plan adjust treatment plan ● Refer to treatment procedure Refer to treatment procedure

The Rule of Drug TreatmentThe Rule of Drug Treatment

Selective rule of Selective rule of antipsychoticsantipsychotics

YESYES EffectiveEffective

SafeSafe

EconomicEconomic

ConvenientConvenient

SimpleSimple

NONO EPSEPS

ProlectinProlectin

Combine Combine

Anticholine drugsAnticholine drugs

Weight gain, etc. Weight gain, etc.

Treatment ProcessTreatment Process

Acute phaseAcute phase ：： 6-12W6-12W

Continue phase Continue phase ：： 4-6 M4-6 M

Maintain phase Maintain phase ：： DifferentDifferent

依从性降低自杀风险

处理应激性生活事件治疗物质滥用

增强患者对社区生活的适应能力提供支持减少应激

促进痊愈的进程继续减少症状

改善功能水平提高生活质量确保症状的缓解

Time

实现个人实现个人的潜能的潜能

Schizophrenia: Treatment Process Schizophrenia: Treatment Process and Targetand Target

规律用药副反应

改善依从性减少复发

防止伤害控制行为

减轻症状的严重程度发现行为扳机

快速恢复至最佳功能状态联合治疗

Acute phase

Continue phase

Maintain phase

Fu

nc

tion

治疗共病减少复发

注意恶化症状的可能因素规律用药副反应

Lehman AF, et al. Am J Psychiatry 2004;161(suppl 2):1-56.

Long-term treatment and prevention is very Long-term treatment and prevention is very importantimportant

-6 -4 -2 0 2 4 6 8 10

Time (year)

Sym

pto

m S

eve

rity

Positive symptomsNegative symptoms（ suicide ）Cognitive impairement

5 “R”5 “R”

ResponseResponse RemissionRemission Recovery: >6MRecovery: >6M RelapseRelapse RecurrenceRecurrence

ObjectiveObjective

Acute phaseAcute phase

1. Symptoms remission1. Symptoms remission ，， clinical recoveryclinical recovery

2. To prepare for recovering social function and 2. To prepare for recovering social function and comeback to society comeback to society

3. To prevent suicidal behavior and aggressive 3. To prevent suicidal behavior and aggressive behaviorbehavior

4. Decrease side effect 4. Decrease side effect

Continue phaseContinue phase 1. To prevent relapse1. To prevent relapse2. 2. To To Comeback to societyComeback to society3.To control post-schizophrenic depressive symptoms and 3.To control post-schizophrenic depressive symptoms and compulsive symptomscompulsive symptoms4. 4. To prevent suicideTo prevent suicide5. To control and 5. To control and prevent side eeffects in long-eterm prevent side eeffects in long-eterm treatment,such as: treatment,such as: EPSEPS 、、 TDTD 、溢乳、、溢乳、 weight gain, weight gain, 糖脂代谢障糖脂代谢障碍、碍、 EKG changesEKG changes

ObjectiveObjective

Maintain phaseMaintain phase 1. To prevent recurrence and deterioration1. To prevent recurrence and deterioration2. To prove compliance2. To prove compliance3. To recover social function3. To recover social function4. To prove the ability to copy with physical and 4. To prove the ability to copy with physical and psychological stress psychological stress

ObjectiveObjective

Treatment Treatment Strategy

First episode and acute episode of recurrent patientsFirst episode and acute episode of recurrent patients 1. Make a comprehensive examination and make an evaluation 1. Make a comprehensive examination and make an evaluation in baselinein baseline

2. Drug treatment 4-6 weeks2. Drug treatment 4-6 weeks

3. To select treatment place according to symptoms and family 3. To select treatment place according to symptoms and family conditioncondition

4. Family education and psychotherapy4. Family education and psychotherapy


Continue phaseContinue phase 1. Not to change drug doses , 4-6 M1. Not to change drug doses , 4-6 M

2. Treatment place: habilitation ward, base, society, family, 2. Treatment place: habilitation ward, base, society, family, outpatient , etc.outpatient , etc.

3. Family education and psychotherapy3. Family education and psychotherapy


Maintain phaseMaintain phase1. 1. Adjust drug doses Adjust drug doses

2. 2. ≥≥ 2-5 years 2-5 years

3. Treatment place: family, outpatient , society 3. Treatment place: family, outpatient , society

4. Family education, psychotherapy and social support4. Family education, psychotherapy and social support

Chronic Patients Chronic Patients

1. To improve effective: doses, drug, combine1. To improve effective: doses, drug, combine

2. Follow up, adjust treatment plane according to illness2. Follow up, adjust treatment plane according to illness

3. Treatment place: family, outpatient, society , 3. Treatment place: family, outpatient, society , habilitation ward, basehabilitation ward, base

4. Psychotherapy and social support4. Psychotherapy and social support

1. Rediagnosis1. Rediagnosis

2. Evaluate drug concentration2. Evaluate drug concentration

3. Remake treatment plan3. Remake treatment plan

4. 4. ≥≥2~52~5 年年

Refractory Chronic PatientsRefractory Chronic Patients

Clinical treatment methodsClinical treatment methods

The acute phase of treatmentThe acute phase of treatment

Oral, the amount of slow ,1-2 weeks to increase the Oral, the amount of slow ,1-2 weeks to increase the

effective dose.effective dose.

Invalid :4-6 weeks to consider dressing change. Invalid :4-6 weeks to consider dressing change.

Ease: the consolidation of 4-6 monthsEase: the consolidation of 4-6 months

Maintenance treatment: dose for the treatment dose Maintenance treatment: dose for the treatment dose

of 1 / 4 to 2 / 3. Need at least two to three years, or of 1 / 4 to 2 / 3. Need at least two to three years, or

even life-long medication.even life-long medication.

Choosing an Antipsychotic AgentChoosing an Antipsychotic Agent 1. In general, the choice of neuroleptic should be made1. In general, the choice of neuroleptic should be made based on past history of neuroleptic response and sidebased on past history of neuroleptic response and side effects. effects. 2. Atypical antipsychotics have gained acceptance as first-2. Atypical antipsychotics have gained acceptance as first- line drugs for treatment of psychosis. They provide aline drugs for treatment of psychosis. They provide a superior long-term outcome in treatment of schizophreniasuperior long-term outcome in treatment of schizophrenia compared to typical antipsychotics. At least two weeks ofcompared to typical antipsychotics. At least two weeks of treatment is required before a significant antipsychotictreatment is required before a significant antipsychotic effect is achieved. effect is achieved.

3. Poor response of negative symptoms (affective 3. Poor response of negative symptoms (affective flattening)flattening)

is an indication for a trial of an atypical agent. Negativeis an indication for a trial of an atypical agent. Negative symptoms can be caused by treatment with typicalsymptoms can be caused by treatment with typical neuroleptics.neuroleptics. 4. Patients with tardive dyskinesia (TD) should be 4. Patients with tardive dyskinesia (TD) should be

consideredfor treatment with an atypical agent to avoid consideredfor treatment with an atypical agent to avoid progression ofprogression of

neurological impairment.neurological impairment. a. Clozapine is not associated with tardive dyskinesia.a. Clozapine is not associated with tardive dyskinesia. b. Olanzapine (Zyprexa), risperidone (Risperdal),b. Olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel) and ziprasidone (Geodon) havequetiapine (Seroquel) and ziprasidone (Geodon) have significantly reduced incidences of tardive dyskinesia.significantly reduced incidences of tardive dyskinesia.

EfficacyEfficacy

1. Positive Symptoms: With the exception of clozapine, no1. Positive Symptoms: With the exception of clozapine, no differences have been clearly shown in the efficacy ofdifferences have been clearly shown in the efficacy of typical and atypical agents in the treatment of positivetypical and atypical agents in the treatment of positive symptoms (eg, hallucinations, delusions, disorganization).symptoms (eg, hallucinations, delusions, disorganization). Clozapine is more effective than typical agents.Clozapine is more effective than typical agents. 2. Negative Symptoms: Atypical agents may be more2. Negative Symptoms: Atypical agents may be more effective in the treatment of negative symptoms (eg,effective in the treatment of negative symptoms (eg, affective flattening, anhedonia, avolition) associated withaffective flattening, anhedonia, avolition) associated with psychotic disorders.psychotic disorders.

3. Treatment-Resistant Psychosis: Clozapine is the only3. Treatment-Resistant Psychosis: Clozapine is the only antipsychotic with substantial data to support efficacy inantipsychotic with substantial data to support efficacy in treatment-resistant psychosis. Thirty percent of poortreatment-resistant psychosis. Thirty percent of poor responders to typical agents show significant improvementresponders to typical agents show significant improvement when treated with clozapine.when treated with clozapine. 4. Bipolar Disorder: Quietapine, olanzapine and risperidone4. Bipolar Disorder: Quietapine, olanzapine and risperidone are FDA-approved for the treatment of acute mania.are FDA-approved for the treatment of acute mania. Substantial data also supports the efficacy of ziprasidoneSubstantial data also supports the efficacy of ziprasidone and aripiprazole. Olanzapine has an indication for mainte-and aripiprazole. Olanzapine has an indication for maintenance treatment of bipolar disorder. nance treatment of bipolar disorder.

QuetiapineQuetiapine

Class: Dibenzothiazepine.Class: Dibenzothiazepine. Mechanism: Quetiapine (Seroquel) is an antagonist at theMechanism: Quetiapine (Seroquel) is an antagonist at the

serotonin-2A, dopamine-2, alpha-1 and 2, and histamine-1serotonin-2A, dopamine-2, alpha-1 and 2, and histamine-1

receptors.receptors. Preparations: 25, 100, 200, and 300 mg tablets.Preparations: 25, 100, 200, and 300 mg tablets. Dosage: Dosage:

Initial dosage for acute psychosis: 100 mg bid, increased byInitial dosage for acute psychosis: 100 mg bid, increased by

50-100 mg every 1 to 3 days to a total daily dose of 600-800 mg50-100 mg every 1 to 3 days to a total daily dose of 600-800 mg Elderly: Clearance is reduced by 40% in elderly; dosage shouldElderly: Clearance is reduced by 40% in elderly; dosage should

be reduced in the elderly.be reduced in the elderly.

Clinical GuidelineClinical Guideline

A. May be effective for primary negative symptoms of A. May be effective for primary negative symptoms of schizo-phrenia. Well tolerated. No anticholinergic side schizo-phrenia. Well tolerated. No anticholinergic side effects. Very low incidence of extrapyramidal effects. Very low incidence of extrapyramidal symptoms. No sustained elevation of prolactin. symptoms. No sustained elevation of prolactin. Requires bid or tid dosing. Patients should be Requires bid or tid dosing. Patients should be monitored for type II diabetes, hyperlipidemia and monitored for type II diabetes, hyperlipidemia and other metabolic side effects.other metabolic side effects.

B. There is significant off-label usage of quetiapine at B. There is significant off-label usage of quetiapine at much lower doses for agitation associated with much lower doses for agitation associated with dementia, delirium, anxiety disorders, insomnia and dementia, delirium, anxiety disorders, insomnia and borderline personality disorder.borderline personality disorder.

Side-Effect ProfileSide-Effect Profile

A. Orthostatic hypotension may occur during initial A. Orthostatic hypotension may occur during initial dose titration due to alpha-blockade. Somnolence dose titration due to alpha-blockade. Somnolence and weight gain may occur. Dyspepsia, abdominal and weight gain may occur. Dyspepsia, abdominal pain, and dry mouth may also occur.pain, and dry mouth may also occur.

B. There are reports of new onset diabetes and B. There are reports of new onset diabetes and diabetic ketoacidosis. diabetic ketoacidosis.

ZiprasidoneZiprasidone

A. Class: Benzisothiazolyl piperazine.A. Class: Benzisothiazolyl piperazine. B. Indications: Psychotic disorders.B. Indications: Psychotic disorders. C. Mechanism: D2, D3, 5HT2A, 5HT1A antagonism; also blocks C. Mechanism: D2, D3, 5HT2A, 5HT1A antagonism; also blocks

reuptake of monoamines.reuptake of monoamines. D. Preparations: 20,40, 60 and 80 mg capsules, IM formulation D. Preparations: 20,40, 60 and 80 mg capsules, IM formulation

(acute use): 20 mg/mL single-dose vial.(acute use): 20 mg/mL single-dose vial. E. Maintenance Dosage: Target dose is 80 mg bid; some patients E. Maintenance Dosage: Target dose is 80 mg bid; some patients

benefit from doses greater than 160 mg/day.benefit from doses greater than 160 mg/day. F. IM Preparation: 10 mg IM every 2 hours or 20 mg IM every 4 F. IM Preparation: 10 mg IM every 2 hours or 20 mg IM every 4

hours to maximum daily dose of 40 mg.hours to maximum daily dose of 40 mg. G. Therapeutic Level: Not established.G. Therapeutic Level: Not established. H. Metabolism: Inactive metabolites, half-life 4 hours. Low potential H. Metabolism: Inactive metabolites, half-life 4 hours. Low potential

for drug interactions.for drug interactions.

Clinical GuidelinesClinical Guidelines

A. Very low incidence of extrapyramidal symptoms. A. Very low incidence of extrapyramidal symptoms. Prolactin elevation is minimal. The incidence of weight Prolactin elevation is minimal. The incidence of weight gain, lipid abnormalities and glucose intolerance is lower gain, lipid abnormalities and glucose intolerance is lower than that seen with other atypical antipsychotics.than that seen with other atypical antipsychotics.

B. While there are no reports linking ziprasidone to cardiac B. While there are no reports linking ziprasidone to cardiac arrhythmias, caution should be exercised in patients with arrhythmias, caution should be exercised in patients with pre-existing increased QT interval (from medications or pre-existing increased QT interval (from medications or cardiac disease). These patients should have a baseline cardiac disease). These patients should have a baseline ECG. QT prolongation has not been observed with the IM ECG. QT prolongation has not been observed with the IM formulation.formulation.

C. Side-Effect Profile: Dizziness, nausea, and postural C. Side-Effect Profile: Dizziness, nausea, and postural hypotension are the most common side effects. Prolactin hypotension are the most common side effects. Prolactin elevation can occur. Sedation is more common with the IM elevation can occur. Sedation is more common with the IM preparation.preparation.

Adverse Reactions of Antipsychotics Adverse Reactions of Antipsychotics

Side Effects of AntipsychoticsSide Effects of Antipsychotics

GPT↑

Side Effects of Antipsychotics

Anticholine EPS Prolactin↑

TD

Sedation

Weight gain

Diabetes

Thromboembolism

hypoleucocytosis Epilepsy

postural hypotension

Long Q-Tc

‘‘After Casey D. J Clin Psychiatry 1996; 57(11): 40-5;’ Hagg S et al. LancetAfter Casey D. J Clin Psychiatry 1996; 57(11): 40-5;’ Hagg S et al. Lancet 2000; 355: 1155-6; Wirshing DA et al. Biol Psychiatry 1998; 44(8): 778-832000; 355: 1155-6; Wirshing DA et al. Biol Psychiatry 1998; 44(8): 778-83

Side Effects of AntipsychoticsSide Effects of Antipsychotics

典型药物典型药物非典型药物非典型药物

CLZCLZ RISRIS OLZOLZ QTPQTP

AgitationAgitation +→+++→++ OO ++++ ++ ++

AgranulocytosisAgranulocytosis（粒细胞缺乏症）（粒细胞缺乏症） RareRare ++++++ RareRare RareRare RareRare

Anticholinergic effectsAnticholinergic effects +→++++→+++ ++++++ ±± ++++ ++

AST/ALT↑AST/ALT↑ ++ ++ OO ++ ++

EPSEPS +→++++→+++ OO ++ OO OO

Nausea/dyspepsiaNausea/dyspepsia ++ OO ±± ++ OO

Othostatic hypotensionOthostatic hypotension +→++++→+++ ++++++ ++ ++++ ++++

Prolactin↑Prolactin↑ +→+++→++ OO ++++ ++ OO

SedationSedation ++→+++++→+++ ++++++ ++ ++++ ++++

SeizuresSeizures ++ ++++++ OO ++ OO

TDTD ++++++ OO ±± ?? ??

Weight gainWeight gain +→+++→++ ++++++ ++ ++++ ++

AkathisiaAkathisia DystoniaDystonia ParkinsonismParkinsonism Tardive Dyskinesia (TD) Tardive Dyskinesia (TD)

Extrapyramidal Side Effects Extrapyramidal Side Effects

Extrapyramidal Side Effects Extrapyramidal Side Effects

AkathisiaAkathisia （静坐不能）：心得安、减药（静坐不能）：心得安、减药 Parkinsonism Parkinsonism （类帕金森症）：安坦（类帕金森症）：安坦 Tardive Dyskinesia (TD Tardive Dyskinesia (TD ）迟发性运动障碍：预防）迟发性运动障碍：预防 Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome （恶性综合征）（恶性综合征）

意识障碍、肌肉强直、高热、自主神经功能紊乱意识障碍、肌肉强直、高热、自主神经功能紊乱

停药、支持性治疗停药、支持性治疗

肌松剂硝苯呋海因、促进中枢肌松剂硝苯呋海因、促进中枢 DADA 功能的溴隐功能的溴隐亭亭

Acute DystoniaAcute Dystonia

early: arise after the first few doses (90% occur within early: arise after the first few doses (90% occur within

first 3 days) first 3 days)

high-potency medications ,young age, male gender, high-potency medications ,young age, male gender,

high doses, intramuscular administration high doses, intramuscular administration sustained spastic contraction of discrete muscle groups sustained spastic contraction of discrete muscle groups

不由自主的、奇特的表现，包括眼上翻、斜颈、颈后倾、面不由自主的、奇特的表现，包括眼上翻、斜颈、颈后倾、面部怪相和扭曲、吐舌、张口困难、角弓反张和脊柱侧弯等。部怪相和扭曲、吐舌、张口困难、角弓反张和脊柱侧弯等。

Differential diagnosisDifferential diagnosis ：： Tetanus, epilepsy, hysteriaTetanus, epilepsy, hysteria TreatmentTreatment ：： hyoscin;artane, Decrease doses, change artane, Decrease doses, change

agentagent

Akathisia Akathisia 静坐不能静坐不能

在治疗在治疗 11 ～～ 22周后最为常见，发生率约为周后最为常见，发生率约为 20%20% 表现为无法控制的激越不安、不能静坐、反复走动或原地踏表现为无法控制的激越不安、不能静坐、反复走动或原地踏步。步。

误诊为精神病性激越或精神病加剧误诊为精神病性激越或精神病加剧处理：苯二氮卓类药和处理：苯二氮卓类药和受体阻滞剂如普萘洛尔受体阻滞剂如普萘洛尔抗胆碱能药通常无效。抗胆碱能药通常无效。有时需减少抗精神病药剂量，或选用锥体外系反应低的药物。有时需减少抗精神病药剂量，或选用锥体外系反应低的药物。

ParkinsonismParkinsonism 类帕金森症类帕金森症最为常见最为常见 ,1,1 ～～ 22月发生，发生率可高达月发生，发生率可高达 56%,56%, 女性更常见女性更常见老年患者常见并因淡漠、抑郁或痴呆而误诊老年患者常见并因淡漠、抑郁或痴呆而误诊表现可归纳为：运动不能、肌张力高、震颤和自主神经功表现可归纳为：运动不能、肌张力高、震颤和自主神经功

能紊乱。最初始的形式是运动过缓，体征上主要为手足震能紊乱。最初始的形式是运动过缓，体征上主要为手足震颤和肌张力增高，严重者有协调运动的丧失、僵硬、佝偻颤和肌张力增高，严重者有协调运动的丧失、僵硬、佝偻姿势、慌张步态、面具脸、粗大震颤、流涎和皮脂溢出。姿势、慌张步态、面具脸、粗大震颤、流涎和皮脂溢出。

处理：服用抗胆碱能药物盐酸苯海索，抗精神病药物的使处理：服用抗胆碱能药物盐酸苯海索，抗精神病药物的使用应缓慢加药或使用最低有效剂量。用应缓慢加药或使用最低有效剂量。

tardive dyskinesia, TDtardive dyskinesia, TD 迟发性运动障迟发性运动障碍碍

多见于持续用药几年后，极少数可能在几个月后发生。用药多见于持续用药几年后，极少数可能在几个月后发生。用药时间越长，发生率越高。女性稍高于男性，老年和脑器质性时间越长，发生率越高。女性稍高于男性，老年和脑器质性患者中多见。患者中多见。

不自主的、有节律的刻板式运动不自主的、有节律的刻板式运动 ,, 严重程度波动不定，睡眠严重程度波动不定，睡眠时消失、情绪激动时加重。时消失、情绪激动时加重。 TDTD最早体征常是舌或口唇周围最早体征常是舌或口唇周围的轻微震颤。的轻微震颤。

处理：尚无有效治疗药物，关键在于预防、使用最低有效剂处理：尚无有效治疗药物，关键在于预防、使用最低有效剂量或换用锥体外系反应低的药物。抗胆碱能药物会促进和加量或换用锥体外系反应低的药物。抗胆碱能药物会促进和加重重 TDTD ，应避免使用。早期发现、早期处理有可能逆转，应避免使用。早期发现、早期处理有可能逆转 TDTD 。。

Neuroleptic Malignant Syndrome, NMS Neuroleptic Malignant Syndrome, NMS 恶性综合征恶性综合征

少见、严重少见、严重意识波动、肌肉强直、高热和自主神经功能不稳定意识波动、肌肉强直、高热和自主神经功能不稳定最常见于氟哌啶醇、氯丙嗪和氟奋乃静等药物治疗时。药物加最常见于氟哌啶醇、氯丙嗪和氟奋乃静等药物治疗时。药物加

量过快、用量过高、脱水、营养不足、合并躯体疾病以及气候量过快、用量过高、脱水、营养不足、合并躯体疾病以及气候炎热等因素，可能与恶性综合征的发生、发展有关。可以发现炎热等因素，可能与恶性综合征的发生、发展有关。可以发现肌酸磷酸激酶肌酸磷酸激酶 (CPK)(CPK) 浓度升高，但不是确诊的指征。浓度升高，但不是确诊的指征。

处理是停用抗精神病药物，给予支持性治疗。可以使用肌肉松处理是停用抗精神病药物，给予支持性治疗。可以使用肌肉松弛剂硝苯呋海因和促进中枢多巴胺功能的溴隐亭治疗。弛剂硝苯呋海因和促进中枢多巴胺功能的溴隐亭治疗。

Other Neurological Adverse Effects Other Neurological Adverse Effects

Sedation Sedation DizzinessDizziness clumsyclumsy Seizures Seizures activationactivation anxietyanxiety agitationagitation

Cardiovascular side EffectsCardiovascular side Effects

ECG Changes ECG Changes Orthostatic (Postural) HypotensionOrthostatic (Postural) Hypotension 直立性低血压直立性低血压 TachycardiaTachycardia 心动过速心动过速 Myocarditis/cardiomyopathyMyocarditis/cardiomyopathy 心肌炎和心肌病 Sudden Unexplained Death Sudden Unexplained Death 猝死猝死

Anticholinergic side effects Anticholinergic side effects

10%–50% 10%–50% impaired learning and memory and slowed cognition. impaired learning and memory and slowed cognition. confusion, delirium, somnolence, and hallucinations. confusion, delirium, somnolence, and hallucinations. Dry mouth ， blurred vision ，， dysuria ， constipation

Weight gain and metabolic abnormalitiesWeight gain and metabolic abnormalities

Weight gain Weight gain Hyperprolactin Hyperprolactin hyperglycemiahyperglycemia 高血糖症高血糖症 diabetes mellitus diabetes mellitus

Liver effects Liver effects

reversible elevations of liver enzyme levels reversible elevations of liver enzyme levels cholestatic jaundice 阻塞性黄疸 0.1 to 0.5% hepatotoxicity hepatotoxicity nausea nausea FeverFever abdominal painabdominal pain rash rash

Hematological EffectsHematological Effects 血液学副反应

Agranulocytosis 粒性白血球缺乏症 neutropenianeutropenia 嗜中性白血球减少症 LeukopeniaLeukopenia 白血球减少症 LeukocytosisLeukocytosis 白细胞增多 ThrombopeniaThrombopenia 血小板减少症

Skin and Eye Effects Skin and Eye Effects

retinal pigmentationretinal pigmentation 视网膜色素沉着

Effects on Sexual FunctionEffects on Sexual Function

Pregnancy and Lactation Pregnancy and Lactation Overdosage Overdosage Tolerance, Dependence, and Withdrawal Tolerance, Dependence, and Withdrawal

Symptoms Symptoms

OverdoseOverdose

1. Death is uncommon with antipsychotic overdose. Risk of1. Death is uncommon with antipsychotic overdose. Risk of fatality is increased with concurrent use of alcohol or otherfatality is increased with concurrent use of alcohol or other CNS depressants.CNS depressants. 2. Mesoridazine, pimozide and thioridazine are associated2. Mesoridazine, pimozide and thioridazine are associated with a greatest risk of fatality because of heart block andwith a greatest risk of fatality because of heart block and ventricular tachycardia.ventricular tachycardia. 3. CNS depression, hypotension, seizures, fever, ECG3. CNS depression, hypotension, seizures, fever, ECG changes, hypothermia, and hyperthermia are possible.changes, hypothermia, and hyperthermia are possible. 4. Treatment may include gastric lavage, catharsis, IV4. Treatment may include gastric lavage, catharsis, IV diazepam for treatment of seizure, and medical treatmentdiazepam for treatment of seizure, and medical treatment of hypotension.of hypotension.

Adverse Reactions of antipsychotic agentsAdverse Reactions of antipsychotic agents

11 受体阻断作用受体阻断作用

镇静、体位性低血压、心动过速、性功能减退镇静、体位性低血压、心动过速、性功能减退胆碱能受体胆碱能受体 MM11 阻断作用阻断作用

口干、便秘、排尿困难、视物模糊、记忆障碍口干、便秘、排尿困难、视物模糊、记忆障碍组胺受体组胺受体 HH11 阻断作用阻断作用

镇静作用、体重增加镇静作用、体重增加

课后思考题课后思考题

什么是抗精神病药？什么是抗精神病药？抗精神病药按药理作用分类有那些？抗精神病药按药理作用分类有那些？试举出六种常用的抗精神病药？试举出六种常用的抗精神病药？抗精神病药的临床适应症有哪些？抗精神病药的临床适应症有哪些？抗精神病药常见的副作用有哪些？如何处理？抗精神病药常见的副作用有哪些？如何处理？

chapter 6 antipsychotic drugs

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