精神障碍药物治疗2018——精神分裂症谱系

,曹 江丽水第二人民医院六病区,精神障碍药物治疗（2018）精神分裂症谱系（Drug Treatment of Mental Disorder：Schizophrenia Spectrum),Resourses available to reference,Stahl精神药理学精要：神经科学基础与临床应用,Stahl精神药理学精要：处方指南（第二版）,Stahls Essential Psychopharmacology :Prescribers Guide (Fifth Edition),中华精神科杂志,最新的药物说明书,D3,D2,D4,D1,2,1,H1,M3,M1,X,PA,5-HT1A,5-HT2A,5-HT2C,5-HT3,5-HT6,5-HT7,CLOZAPINE,各种药物的结合特性由于不同实验室技术和样本的原因都有很大的不同，这将不断修订并更新。,Amisulpride（阿米舒必利，又名氨磺必利）,How the Drug Works,D3,D2,Theoretically blocks presynaptic dopamine 2 receptors at low doses Theoreticallly blocks postsynaptic dopamine 2 receptors at higher doses May be a partial agonist at dopamine 2 receptors ,which would theoretically reduce dopamine output when dopamine concentrations are high and increase dopamine output when dopamine concentrations are low,1,2,Blocks dopamine 3 recepors ,which may contribute to its clinical actions Unlike other atypical antipsychotics at serotonin 2A or serotonin 1A receptors Dose have antagonist actions at serotonin 7 receptors and serotonin 2B receptors ,which may contribute to antidepressant effects,3,Commonly Prescribed for(bold for FDA apprved),Schizophrenia,acute and chronic (outside of U.S.,especially Europe),Dysthymia,CFDA:INDICATIONS,用来治疗精神疾患，尤其是伴有阳性症状（例如：谵妄、幻觉、认知障碍）和/或阴性症状（例如：反应迟缓、情感淡漠及社会能力退缩）的急性或慢性精神分裂症，也包括以阴性症状为主的精神病患。,U.S. FDA Vs CFDA:DOSING AND USE,U.S. FDA: Schizophrenia:400800mg/day in 2 doses Negative sympotoms only：50300mg/day Dysthymia:50mg/day,CFDA : 通常情况下，若每天剂量小于或等于400mg，应一次服完；若每天超过400mg，应分为两次服用。 阴性症状占优势阶段，推荐剂量为50300mg/d。剂量应根据个人情况进行调整。最佳剂量约为100mg/d。 阳性及阴性症状混合阶段，治疗初期，应主要控制阳性症状，剂量可为：400800mg/d。然后根据病人的反应调整剂量至最小有效剂量。,U.S. FDA Vs CFDA:CONTRAINDICATIONS,1.嗜铬细胞瘤2.泌乳素相关肿瘤3.怀孕或哺乳4、使用能显著延长QTc间期的药物，如：哌迷清、硫利达嗪；某些抗心律失常药物，如：奎尼丁、丙吡胺、胺碘酮、索他洛尔；某些抗微生物药物，如：莫西沙星、司帕沙星（禁忌 Vs 不建议）5.有QTc间期延长或心律失常、近期心肌梗死、失代偿性心力衰竭病史（禁忌 Vs 不建议）6.西沙比利、静脉注射红霉素或喷他脒（禁忌 Vs 不建议）7.儿童（18岁 Vs 15岁）8.对氨磺必利过敏9.严重肾功能不全（无 Vs 禁忌）10.联合用于舒托必利、多巴胺激动剂如金刚烷胺、无水吗啡、溴隐亭、普拉克索等），除了用于治疗帕金森病患者（无 Vs 禁忌）,Aripiprazole（阿立哌唑）,How the Drug Works,D3,D2,PA,5-HT1A,5-HT2A,PA,5-HT2c？,5-HT7？,Partial agonism at dopamine 2 receptors Theoretically reduce dopamine output when dopamine concentrations are high,thus improving positive symptoms and mediating antipsychotic actions,1,Theoretically increase dopamine output when dopamine concentrations are low,thus improving cognitive ,negative and mood symptoms,2,Actions at dopamine 3 receptors could theoreticallyContribute to aripiprazoles efficacy Partial agonist at 5-HT1A receptors may be relevant at clinical doses,3,4,Blockade of serotonin type 2A recepors may contribute to at clinical doses to cause enhancement of dopamine release in certain brain regions , thus reducing motor side effects and possibly improving cognitive and affective symptoms,5,Blockade of serotonin type 2C and 7 receptors as well as 5-HT1A receptors may contribute to antidepression actions,6,Commonly Prescribed for(bold for FDA apprved),Schizophrenia（ages 13 and older）(Abilify,Abilify Maintena),Bipolar depression,Maintaining stability in schizophrenia,Acute mania/mixed mania(age 10 and older;monotherapy and adjunct),Bipolar maintenance (monotherapy and adjunct),Depression (adjunct),Autusm-related irritability in children ages 6 to 17,Acute agitation associated with schizophrenia or bipolar disorder(IM),Other psychotic disorders,Behavioral disturbances in dementias,Behavioral disturbances in children and adolescents.,Disorders associated with problems with impulse control,Commonly Prescribed for(bold for FDA apprved),CFDA:INDICATIONS,用于治疗精神分裂症。 在精神分裂症的短期（4周和6周）对照实验中确立了阿立哌唑治疗精神分裂症的疗效。选择阿立哌唑用于长期治疗的医生应定期重新评估该药对个别患者的长期疗效。,U.S. FDA Vs CFDA:DOSING AND USE,U.S. FDA: 15-30mg/day for schizophrenia and bipolar 2-10mg/day for augmenting SSRIs/SNRIs in depression 300-400mg/4 weeks (depot) 441mg/662mg/882mg,once monthly(IM)；882mg，once/6 weeks(IM);1064mg，once/2 weeks (IM),CFDA : 成人：口服，每日一次。起始剂量为10mg，用药两周后，可根据个体的疗效和耐受性情况逐渐增加剂量，最大可增至30mg。此后，可维持此剂量不变。每日最大剂量不应超过30mg。,U.S. FDA Vs CFDA:CONTRAINDICATIONS,有证据表明对阿立哌唑过敏,Clozapine（氯氮平）,How the Drug Works,D3,D2,D4,D1,2,1,H1,M3,M1,X,PA,5-HT1A,5-HT2A,5-HT2C,5-HT3,5-HT6,5-HT7,Blocks dopamine 2 receptors,reducing positive symptoms of psychosis and stabilizing affective symptoms Blocks serotonin 2A recepors,causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms Interactions at a myriad of other neurotransmitter receptors may contribute to clozapines efficacy,1,2,3,Specifically,interactions at 5-HT2c and 5-HT1A receptors may contribute to efficacy for cognitive and affective symptoms in some patients Mechanism of efficacy for psychotic patients who do not respond to conventional antipsychotics is unkown,4,Commonly Prescribed for(bold for FDA apprved),Treatment-resistant schizophrenia,Treatmentresistant bipolar disorder,Reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffectiv disorder,Violent aggressive patients with psychosis and other brain disorders not responsive to other treatments,CFDA:INDICATIONS,本品不仅对精神病阳性症状有效，对阴性症状也有一定效果。适用于急性与慢性精神分裂症的各个亚型，对幻觉妄想型、青春型效果好。也可以减轻与精神分裂症有关的情感症状（如：抑郁、负罪感、焦虑）。对一些传统抗精神病药治疗无效或疗效不好的病人，改用本品可能有效。也用于治疗躁狂症或其他精神病性障碍的兴奋躁动和幻觉妄想。因导致粒细胞减少症，一般不宜作为首选药。,U.S. FDA Vs CFDA:DOSING AND USE,U.S. FDA: 300450mg/day Maximum dose generally 900mg/day,CFDA : 口服从小剂量开始，首次剂量为一次25mg，一日23次，逐渐缓慢增加至常用治疗量一日200400mg，高量可达一日600mg。维持量为一日100200mg。,U.S. FDA Vs CFDA:CONTRAINDICATIONS,1.骨髓组织增值障碍2.尚未被控制的癫痫发作3.粒细胞减少4.麻痹性肠梗阻5.中枢神经系统抑制（禁忌VS慎用）6.对氯氮平过敏7.严重心、肝、肾疾患（无 VS 禁忌）8.昏迷（无 VS 禁忌）9.谵妄（无 VS 禁忌）10.低血压（无 VS 禁忌）11.青光眼（无 VS 禁忌）,Olanzapine（奥氮平）,How the Drug Works,D3,D2,D4,D1,1,H1,M3,M1,X,5-HT2A,5-HT2C,5-HT3,5-HT6,Blocks dopamine 2 receptors,reducing positive symptoms of psychosis and stabilizing affective symptoms Blocks serotonin 2A recepors,causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms Interactions at a myriad of other neurotransmitter receptors may contribute to olanzapines efficacy,1,2,3,Specifically,interactions at 5-HT2c and 5-HT1A receptors may contribute to efficacy for cognitive and affective symptoms in some patients 5-HT2c antagonist actions plus serotonin reuptake blockade of fluoxetine add to the actions of olanzapine when given as Symbyax(olanzapine-fluoxetine combination),Commonly Prescribed for(bold for FDA apprved),Schizophrenia (ages 13 and older),Maintaining response in schizophrenia,Bipolar maintenance,Acute agitation associated with schizophrenia(intramuscular),Acute mania/mixed mania(monotherapy and adjunct to lithium or valproate)(ages 13 and older),Acute agitation associated with bipolar mania(intramuscular),Bipolar depression in combination with fluoxetine (Symbyax),Commonly Prescribed for(bold for FDA apprved),Other psychotic disorders,Behavioral disturbances in dementias,Disorders associated with problems with impulse control,Treatment-resistant depression in combination with fluoxetine (Symbyax),Behavioral disturbances in children and adolescents,Borderline personality disorder,CFDA:INDICATIONS,用于治疗精神分裂症初始化治疗有效的患者，奥氮平在维持治疗期间能够保持其临床治疗效果。用于治疗中、重度躁狂发作。对奥氮平治疗有效的躁狂发作患者，可用于预防双相情感障碍的复发。,U.S. FDA Vs CFDA:DOSING AND USE,U.S. FDA: 1020mg/day（oral or intramuscular） 612mg olanzapine/2550mg fluoxetine (olanzapine-fluoxetine combination) 210300mg/2 weeks (depot),CFDA : 精神分裂症：建议起始剂量为10mg/d，每日一次，与进食无关。 躁狂发作：单独用药时起始剂量为每日15mg，合并治疗时每日10mg。预防双相情感障碍复发：推荐起始剂量为10mg/d。 在精神分裂症、躁狂发作和双相情感障碍的预防治疗过程中，根据患者的临床状态调整日剂量为520mg/d。,U.S. FDA Vs CFDA:CONTRAINDICATIONS,1.如果有已知的闭角型青光眼的风险（禁止肌内注射剂型）CFDA:片剂禁止2.有不稳定的健康状况时如：急性心肌梗死、不稳定心绞痛、严重低血压和(或）心动过缓、病窦综合征、近期接受过心脏手术，禁用肌内注射剂型 CFDA:未提及3.有证据表明对奥氮平过敏,Quetiapine（喹硫平）,How the Drug Works,D2,2,1,H1,M3?,M1,X?,PA,5-HT1A,5-HT2A,5-HT2C,5-HT6,5-HT7,NRI,Blocks dopamine 2 receptors,reducing positive symptoms of psychosis and stabilizing affective symptoms Blocks serotonin 2A recepors,causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms Interactions at a myriad of other neurotransmitter receptors may contribute to quetiapines efficacy in,1,2,treatment-resistant depression or bipolar depression especially 5-HT1A partial agonist action,norepinephrine reuptake blockade and 5-HT2C antagonist and 5-HT7 antagonist properties Specifically,actions at 5-HT1A receptors may contribute to efficacy for cognitive and affective symptoms in some patients,especially at moderate to high doses,Commonly Prescribed for(bold for FDA apprved),Acute schizophrenia in adults (quetiapine,quetiapine XR) and ages 1317(quetepine),Acute mania in adults(quetiapine and quetiapine XR,monotherapy and adjunct to lithium or valproate) and ages 1017(quetiapine,monotherapy and adjunct to lithium or valproate),Schizophrenia maintenance(quetiapine XR）,Bipolar maintenance(quetiapine,quetiapine XR),Bipolar depression,(quetiapine,quetiapine XR),Depression(quetiapine,quetiapine XR),Other psychotic disorders,Mixed mania,Behavioral disturbances in dementias,Commonly Prescribed for(bold for FDA apprved),Behavioral disturbances in Parkinsons disease and Lewy body dementia,Psychosis associated with leodopa treatment in Parkinsons disease,Behavioral disturbances in children and aldolescents,Disorders associated with problems with impulse control,Severe treatment-resistant anxiety,CFDA:INDICATIONS,用于治疗精神分裂症,U.S. FDA Vs CFDA:DOSING AND USE,U.S. FDA: 400800mg/day in 1（quetiapine XR）or 2(quetiapine) doses for schizophrenia 400800mg/day in 1（quetiapine XR）or 2(quetiapine) doses for bipolar mania 300mg once daily for bipolar depression,CFDA : 口服。每日总剂量分为2次，饭前或饭后服用。 成人：治疗初期的日总剂量为：第一日50毫克，第二日100毫克，第三日200毫克，第四日300毫克。从第四日后，将剂量逐渐增加到有效剂量范围，一般为每日300450mg。可根据患者的临床反应和耐受性将剂量调整为每日150750毫克。,U.S. FDA Vs CFDA:CONTRAINDICATIONS,有证据表明对喹硫平过敏,Risperidone（利培酮）,How the Drug Works,D2,2,1,5-HT2A,5-HT7,X?,Blocks dopamine 2 receptors,reducing positive symptoms of psychosis and stabilizing affective symptoms Blocks serotonin 2A recepors,causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms Interactions at a myriad of other neurotransmitter receptors may contribute to quetiapines efficacy in,1,2,3,Specifically,5-HT7 antagonist properties may contribute to antidepressant actions,Commonly Prescribed for(bold for FDA apprved),Schizophrenia,ages 13 and older(oral,long-acting microspheres intramuscularly),Delaying relapse in schizophrenia( oral),Acute mania/mixed mania,ages 10 and older (oral,monotherapy and adjunct to lithium or valproate),Autism-related irritability in children ages 516,Other psychotic disorders( oral),Bipolar depression,Bipolar maintenances(long-acting microspheres intramuscularly,monotherapy and adjunct to lithium or valproate),Behavioral disturbances in dementias,Behavioral disturbances in children and adolescents.,Disorders associated with problems with impulse control,Commonly Prescribed for(bold for FDA apprved),CFDA:INDICATIONS,用于治疗急性和慢性精神分裂症以及其它各种精神病性状态的明显的阳性症状（如幻觉、妄想、思维紊乱、敌视、怀疑）和明显的阴性症状（如反应迟钝、情绪淡漠及社交淡漠、少语）。也可减轻与精神分裂症有关的情感症状（如抑郁、负罪感、焦虑）。对于急性期治疗有效的患者，在维持期治疗中，本品可以继续发挥其临床疗效。,U.S. FDA Vs CFDA:DOSING AND USE,U.S. FDA: 2-8mg/day orally for acute psychosis and bipolar disorder 0.5-2.0mg/day orally for children and elderly 25-50 mg depot intramuscularly every 2 weeks,CFDA : 片剂：每日一次或每日两次。推荐起始剂量为一日二次，一次1mg，第二天增加到一日二次，一次2mg；如能耐受，第三天可增加到一日二次，每次3mg。此后，可维持此剂量不变，或根据个人情况进一步调整。调整的时间间隔一般不少于一周。最大有效剂量范围为每日4-8mg。由于对剂量16mg/d的安全性尚未评价，因此每日用药剂量不应超过16mg。 微球:推荐剂量为25mg肌肉注射，每2周1次。某些患者需要更高的剂量，例如37.5mg或50mg。75mg 的剂量没有临床意义。不推荐剂量高于每周50mg,U.S. FDA Vs CFDA:CONTRAINDICATIONS,有证据表明对利培酮过敏,Ziprasidone（齐拉西酮）,How the Drug Works,D3,D2,1,PA,5-HT1A,5-HT2A,5-HT2C,5-HT7,5-HT1D,SRI,NRI,Blocks dopamine 2 receptors,reducing positive symptoms of psychosis and stabilizing affective symptoms Blocks serotonin 2A recepors,causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms Interactions at a myriad of other neurotransmitter receptors may contribute to ziprasidones efficacy in,1,2,3,Specifically,interactions at 5-HT2c and 5-HT1A receptors may contribute to efficacy for cognitive and affective symptoms in some patient