精神分裂症

患者主诉烦躁不安。例如劳拉西泮或普萘洛尔等是治疗期间的常规处方药物；但是支持这一临床实践的证据较少。[222]Barnes TR, Soares-Weiser K, Bacaltchuk J, et al. Central action beta-blockers versus placebo for neuroleptic-induced acute akathisia. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001946.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001946.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15495022?tool=bestpractice.com 在某些情况下，需要减少抗精神病药物的剂量。

由于抗精神病药物的 α-肾上腺素活性导致体位性低血压，通常在起始或加量时出现。[224]Glassman AH. Schizophrenia, antipsychotic drugs, and cardiovascular disease. J Clin Psychiatry. 2005;66 suppl 6:5-10.http://www.ncbi.nlm.nih.gov/pubmed/16107178?tool=bestpractice.com

该并发症通常在药物治疗的前几个小时或前几天短暂出现。任何患者都可能出现低血压，但是老年患者更为敏感。预防措施包括教育患者采用慢动作起身。

Orthostatic hypotension

肌张力障碍指任何横纹肌上不自主的肌肉收缩。静脉或肌内注射苯海拉明或苯甲托品能够在数分钟内逆转肌张力障碍。[225]Gray R, Gournay K. What can we do about acute extrapyramidal symptoms? J Psychiatr Ment Health Nurs. 2000 Jun;7(3):205-11.http://www.ncbi.nlm.nih.gov/pubmed/11249313?tool=bestpractice.com

Dystonias

开始用药后的最初几个月随时可能出现。特异性症状群包括：自主神经功能障碍、肌肉强直、高热及意识障碍。由于能够威胁生命，必须尽早诊断出神经阻滞剂恶性综合征 (NMS)。除了立即停药并静脉输液，患者需要支持性干预，最好送入重症监护病房。[226]Velamoor VR, Swamy GN, Parmar RS, et al. Management of suspected neuroleptic malignant syndrome. Can J Psychiatry. 1995 Nov;40(9):545-50.http://www.ncbi.nlm.nih.gov/pubmed/8574990?tool=bestpractice.com

Neuroleptic malignant syndrome

帕金森样临床现象，包括姿势僵硬、运动流畅性减弱、步子小及面部表情较少。在药物治疗开始时每日给予苯海拉明或苯扎托品，尤其是在使用第一代抗精神病药物时，以期减小帕金森症的风险。[227]Klemp M, Tvete IF, Skomedal T, et al. A review and Bayesian meta-analysis of clinical efficacy and adverse effects of 4 atypical neuroleptic drugs compared with haloperidol and placebo. J Clin Psychopharmacol. 2011 Dec;31(6):698-704.http://www.ncbi.nlm.nih.gov/pubmed/22020356?tool=bestpractice.com

自杀的终生风险约为 5%。[69]Hawton K, Sutton L, Haw C, et al. Schizophrenia and suicide: systematic review of risk factors. Br J Psychiatry. 2005 Jul;187:9-20.http://www.ncbi.nlm.nih.gov/pubmed/15994566?tool=bestpractice.com[68]Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005 Mar;62(3):247-53.http://archpsyc.jamanetwork.com/article.aspx?articleid=208392http://www.ncbi.nlm.nih.gov/pubmed/15753237?tool=bestpractice.com[70]Hor K, Taylor M. Suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol. 2010 Nov;24(4 suppl):81-90.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951591/http://www.ncbi.nlm.nih.gov/pubmed/20923923?tool=bestpractice.com 在初步诊断时及诊断后立刻自杀的风险更高，且也会出现在每次精神病急性发作之后。

Suicide risk management

多达三分之一的精神分裂症患者随时使用毒品。[220]Coyle JT. Substance use disorders and schizophrenia: a question of shared glutamatergic mechanisms. Neurotox Res. 2006 Dec;10(3-4):221-33.http://www.ncbi.nlm.nih.gov/pubmed/17197372?tool=bestpractice.com 物质使用可能在疾病初次发作之前，或者在疾病过程中产生。

Overview of substance abuse and overdose

精神分裂症患者比普通人群吸烟更为严重，且表现出更高的由吸烟相关疾病造成的发病率和死亡率。[221]Tsoi DT, Porwal M, Webster AC. Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD007253.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007253.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450574?tool=bestpractice.com 对于患有精神分裂症吸烟者，安非他酮可能能够减少其烟草使用量并提高禁戒率，并不影响患者症状的稳定性。[221]Tsoi DT, Porwal M, Webster AC. Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD007253.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007253.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450574?tool=bestpractice.com证据 B烟草使用减少及戒烟：有中等质量证据表明对于患有精神分裂症吸烟者，安非他酮可能能够减少其烟草使用量并提高禁戒率，并不影响患者症状的稳定性。[221]Tsoi DT, Porwal M, Webster AC. Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD007253.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007253.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450574?tool=bestpractice.com受试者＜200名的随机对照临床试验（RCT）、受试者＞200名且方法学存在缺陷的随机对照临床试验（RCT）、方法学存在缺陷的系统评价或者高质量的观察性（队列）研究。

Smoking cessation

特征为重复、不自主、无目的的动作。不自主运动量表 (Abnormal Involuntary Movement Scale)[188]Munetz MR, Benjamin S. How to examine patients using the Abnormal Involuntary Movement Scale. Hosp Community Psychiatry. 1988 Nov;39(11):1172-7.http://www.ncbi.nlm.nih.gov/pubmed/2906320?tool=bestpractice.com 是一种很有帮助的工具，可用于持续监测和早期识别迟发性运动障碍。使用高效的抗精神病药存在更大的风险。[223]Cubo E, Gracies JM, Benabou R, et al. Early morning off-medication dyskinesias, dystonia, and choreic subtypes. Arch Neurol. 2001 Sep;58(9):1379-82.http://archneur.jamanetwork.com/article.aspx?articleid=780272http://www.ncbi.nlm.nih.gov/pubmed/11559308?tool=bestpractice.com

与精神分裂症和自杀倾向密切相关。抗抑郁剂治疗的同时可能还需密切评估自杀风险。

Depression

一些药物更易引起体重增加。奥氮平、[128]Buchanan RW, Panagides J, Zhao J, et al. Asenapine versus olanzapine in people with persistent negative symptoms of schizophrenia. J Clin Psychopharmacol. 2012 Feb;32(1):36-45.http://www.ncbi.nlm.nih.gov/pubmed/22198451?tool=bestpractice.com 氯氮平、喹硫平、帕利哌酮和利培酮都能够导致体重增加，并可能导致其他代谢方面的不良反应。[129]Stephenson CM, Pilowsky LS. Psychopharmacology of olanzapine: a review. Br J Psychiatry Suppl. 1999;(38):52-8.http://www.ncbi.nlm.nih.gov/pubmed/10884900?tool=bestpractice.com[130]Leucht S, Kissling W, Davis JM. Second-generation antipsychotics for schizophrenia: can we resolve the conflict? Psychol Med. 2009 Oct;39(10):1591-602.http://www.ncbi.nlm.nih.gov/pubmed/19335931?tool=bestpractice.com[131]Naber D, Lambert M. The CATIE and CUtLASS studies in schizophrenia: results and implications for clinicians. CNS Drugs. 2009 Aug;23(8):649-59.http://www.ncbi.nlm.nih.gov/pubmed/19594194?tool=bestpractice.com 如果出现体重增加 5% 的情况，需考虑换药。[228]Nasrallah H. A review of the effect of atypical antipsychotics on weight. Psychoneuroendocrinology. 2003 Jan;28 suppl 1:83-96.http://www.ncbi.nlm.nih.gov/pubmed/12504074?tool=bestpractice.com

添加托吡酯或二甲双胍，[229]Das C, Mendez G, Jagasia S, et al. Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments. Ann Clin Psychiatry. 2012 Aug;24(3):225-39.http://www.ncbi.nlm.nih.gov/pubmed/22860242?tool=bestpractice.com[230]Mahmood S, Booker I, Huang J, et al. Effect of topiramate on weight gain in patients receiving atypical antipsychotic agents. J Clin Psychopharmacol. 2013 Feb;33(1):90-4.http://www.ncbi.nlm.nih.gov/pubmed/23277264?tool=bestpractice.com 或从一种具有较高体重增加可能性的药物更换为一种具有较低体重增加风险的药物（例如齐呱西酮 [zipraszidone][133]Zhang Y, Dai G. Efficacy and metabolic influence of paliperidone ER, aripiprazole and ziprasidone to patients with first-episode schizophrenia through 52 weeks follow-up in China. Hum Psychopharmacol. 2012 Nov;27(6):605-14.http://www.ncbi.nlm.nih.gov/pubmed/24446539?tool=bestpractice.com）可能是一种有效的体重控制措施，同时还能稳定精神分裂症的症状。[231]Mukundan A, Faulkner G, Cohn T, et al. Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD006629.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006629.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21154372?tool=bestpractice.com

此外，运动结合营养建议能够使患者获益。[229]Das C, Mendez G, Jagasia S, et al. Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments. Ann Clin Psychiatry. 2012 Aug;24(3):225-39.http://www.ncbi.nlm.nih.gov/pubmed/22860242?tool=bestpractice.com

Obesity in adults

需要监测空腹血糖水平和血脂水平。[232]Jin H, Meyer JM, Jeste DV. Atypical antipsychotics and glucose dysregulation: a systematic review. Schizophr Res. 2004 Dec 1;71(2-3):195-212.http://www.ncbi.nlm.nih.gov/pubmed/15474892?tool=bestpractice.com 只有在完成风险效益评估且代谢不良反应被控制后，患者才能继续使用引起代谢异常的药物。[233]Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68 suppl 1:20-27.http://www.ncbi.nlm.nih.gov/pubmed/17286524?tool=bestpractice.com将代谢综合征风险较高的药物（例如奥氮平）替换成风险较低的药物（例如喹硫平或阿立哌唑）可能是一项有效的代谢干预，同时能够稳定精神分裂症的症状。[231]Mukundan A, Faulkner G, Cohn T, et al. Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD006629.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006629.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21154372?tool=bestpractice.com

Metabolic syndrome

症状可分为外周症状（比如：口干、便秘、视力模糊和尿潴留）和中枢症状（比如：谵妄）。

患者通常会对口干之类的副作用产生耐受性。可通过用水漱口或咀嚼无糖口香糖来缓解。对于视力模糊，需暂时减少药物剂量。如果出现急性尿潴留或者谵妄，需停药。

具有较高多巴胺阻断作用的抗精神病药物，例如氟哌啶醇、氟奋乃静和利培酮，能够引起泌乳素升高，出现溢乳、男性乳腺发育症、闭经和性功能障碍。[193]Halbreich U, Kahn LS. Hyperprolactinemia and schizophrenia: mechanisms and clinical aspects. J Psychiatr Pract. 2003 Sep;9(5):344-53.http://www.ncbi.nlm.nih.gov/pubmed/15985953?tool=bestpractice.com 临床医生需降低药物剂量或换药。

西地那非和阿立哌唑的辅助治疗能够改善性功能障碍和（或）降低泌乳素水平。[234]Nunes LV, Moreira HC, Razzouk D, et al. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. J Sex Marital Ther. 2012;38(3):281-301.http://www.ncbi.nlm.nih.gov/pubmed/22533871?tool=bestpractice.com

Assessment of hyperprolactinaemia

已有报道指出，服用抗精神病药物的患者会出现 QT 间期延长、T 波扁平及尖端扭转型室速。[235]Glassman AH, Bigger JT, Jr. Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001 Nov;158(11):1774-82.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.158.11.1774http://www.ncbi.nlm.nih.gov/pubmed/11691681?tool=bestpractice.com 可能需要进行基线 ECG 检查，尤其当存在心血管危险因素（例如存在心血管疾病 [传导异常和/或心脏异常或者查体时发现的危险因素] 个人史）时或者患者为住院人员时。[194]Royal Pharmaceutical Society; British Medical Association. British national formulary. 2017 [internet publication].https://www.medicinescomplete.com/about/publications.htm

大多数抗精神病药物已被报道可能导致粒细胞缺乏症。累积证据显示氯氮平的风险是 0.8%，远远高于其他抗精神病药物。[236]Collaborative Working Group on Clinical Trial Evaluations. Adverse effects of the atypical antipsychotics. J Clin Psychiatry. 1998;59 suppl 12:17-22.http://www.ncbi.nlm.nih.gov/pubmed/9766615?tool=bestpractice.com

只有接受氯氮平治疗的患者才需要常规监测中性粒细胞绝对计数。监测频率为：第一个 6 个月内每周一次，第二个 6 个月内每 2 周一次，并在此后每月一次，无限期监测。

如果患者对至少 2 次足量试用 2 种不同的抗精神病药物治疗无反应，则推荐使用氯氮平。氯氮平治疗需持续至少8周，处方剂量为每日 300~800 mg。[84]Kreyenbuhl J, Buchanan RW, Dickerson FB, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010 Jan;36(1):94-103.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800150/http://www.ncbi.nlm.nih.gov/pubmed/19955388?tool=bestpractice.com 如果到第 6 个月时仍无反应，之后应考虑使用不良反应风险较低的药物。[84]Kreyenbuhl J, Buchanan RW, Dickerson FB, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010 Jan;36(1):94-103.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800150/http://www.ncbi.nlm.nih.gov/pubmed/19955388?tool=bestpractice.com[93]Siskind D, McCartney L, Goldschlager R, et al. Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. Br J Psychiatry. 2016 Nov;209(5):385-92.http://www.ncbi.nlm.nih.gov/pubmed/27388573?tool=bestpractice.com[199]Tandon R, Fleischhacker WW. Comparative efficacy of antipsychotics in the treatment of schizophrenia: a critical assessment. Schizophr Res. 2005 Nov 15;79(2-3):145-55.http://www.ncbi.nlm.nih.gov/pubmed/16139989?tool=bestpractice.com 对药物耐受性精神分裂症，舒必利辅助氯氮平联合用药比氯氮平单药治疗更为有效，[197]Wang J, Omori IM, Fenton M, et al. Sulpiride augmentation for schizophrenia. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD008125.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008125.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20091661?tool=bestpractice.com证据 C药物治疗耐受患者的临床症状改善：有低质量证据表明在对其他抗精神病药物（包括氯氮平）耐受的患者中，舒必利加氯氮平联合用药比氯氮平单药治疗更为有效的改善临床症状。[197]Wang J, Omori IM, Fenton M, et al. Sulpiride augmentation for schizophrenia. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD008125.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008125.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20091661?tool=bestpractice.com低质量的观察性（队列）研究或者受试者＜200名且方法学存在缺陷的随机对照临床试验（RCT）。尽管这一方法的证据是混杂的。[237]Barnes TR, Leeson VC, Paton C, et al. Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness. Health Technol Assess. 2017 Sep;21(49):1-56.https://www.ncbi.nlm.nih.gov/books/NBK453009/http://www.ncbi.nlm.nih.gov/pubmed/28869006?tool=bestpractice.com 一项小型随机对照临床试验中，氯氮平联合氨磺必利治疗发生不良反应的风险，相比氯氮平加安慰剂治疗要更高。[237]Barnes TR, Leeson VC, Paton C, et al. Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness. Health Technol Assess. 2017 Sep;21(49):1-56.https://www.ncbi.nlm.nih.gov/books/NBK453009/http://www.ncbi.nlm.nih.gov/pubmed/28869006?tool=bestpractice.com 虽然大多数不良反应都很轻微，但这些结果提示在临床上若共用氯氮平和氨磺必利，应严密监测联合治疗的安全性和耐受性。