Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Munich (Leucht, Priller); German Center for Mental Health, Munich (Leucht, Priller); Neuropsychiatry, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Disorders, Berlin (Priller); University of Edinburgh and UK Dementia Research Institute, Edinburgh (Priller); Department of Psychiatry, University of Illinois at Chicago (Davis).
Am J Psychiatry. 2024 Oct 1;181(10):865-878. doi: 10.1176/appi.ajp.20240738.
The introduction of the first antipsychotic drug, chlorpromazine, was a milestone for psychiatry. The authors review the history, classification, indications, mechanism, efficacy, side effects, dosing, drug initiation, switching, and other practical issues and questions related to antipsychotics. Classifications such as first-generation/typical versus second-generation/atypical antipsychotics are neither valid nor useful; these agents should be described according to the Neuroscience-based Nomenclature (NbN). Antipsychotic drugs are not specific for treating schizophrenia. They reduce psychosis regardless of the underlying diagnosis, and they go beyond nonspecific sedation. All currently available antipsychotic drugs are dopamine blockers or dopamine partial agonists. In schizophrenia, effect sizes for relapse prevention are larger than for acute treatment. A major unresolved problem is the implausible increase in placebo response in antipsychotic drug trials over the decades. Differences in side effects, which can be objectively measured, such as weight gain, are less equivocal than differences in rating-scale-measured (subjective) efficacy. The criteria for choosing among antipsychotics are mainly pragmatic and include factors such as available formulations, metabolism, half-life, efficacy, and side effects in previous illness episodes. Plasma levels help to detect nonadherence, and once-daily dosing at night (which is possible with many antipsychotics) and long-acting injectable formulations are useful when adherence is a problem. Dose-response curves for both acute treatment and relapse prevention follow a hyperbolic pattern, with maximally efficacious average dosages for schizophrenia of around 5 mg/day risperidone equivalents. Computer apps facilitating the choice between drugs are available. Future drug development should include pharmacogenetics and focus on drugs for specific aspects of psychosis.
第一代抗精神病药物氯丙嗪的问世，标志着精神病学的一个里程碑。本文作者回顾了抗精神病药物的历史、分类、适应证、作用机制、疗效、副作用、剂量、起始用药、换药和其他相关的实际问题和疑问。第一代/典型与第二代/非典型抗精神病药物的分类既不科学也没有意义；这些药物应根据基于神经科学的命名法（NbN）来描述。抗精神病药物并不仅仅是用于治疗精神分裂症的。它们可以减少各种精神疾病的精神病性症状，而不仅仅是起到非特异性镇静作用。目前所有的抗精神病药物都是多巴胺阻滞剂或多巴胺部分激动剂。在精神分裂症中，预防复发的效果比急性期治疗更大。一个尚未解决的主要问题是，几十年来抗精神病药物试验中安慰剂的反应率不可思议地增加。可以客观测量的副作用差异（如体重增加），比基于量表测量的（主观）疗效差异更明确。选择抗精神病药物的标准主要是实际情况，包括可用剂型、代谢、半衰期、既往疾病发作中的疗效和副作用等因素。血浆水平有助于发现不遵医嘱的情况，而每日一次晚间（许多抗精神病药物都可以）给药和长效注射剂型在依从性存在问题时很有用。急性治疗和预防复发的剂量-反应曲线均呈双曲线模式，精神分裂症的最大有效平均剂量约为 5 毫克/天利培酮等效剂量。有助于在药物之间做出选择的计算机应用程序已经问世。未来的药物研发应包括药物遗传学，并专注于针对精神疾病特定方面的药物。
