Meltzer Herbert Y, Gadaleta Erick
Focus (Am Psychiatr Publ). 2021 Jan;19(1):3-13. doi: 10.1176/appi.focus.20200051. Epub 2021 Jan 25.
The beliefs that antipsychotic drugs (APDs) are 1) effective to treat delusions and hallucinations (positive symptoms), 2) that typical and atypical APDs differ in ability to cause extrapyramidal side effects, and 3) that their efficacy as antipsychotics is due to their dopamine D receptor blockade are outmoded concepts that prevent clinicians from achieving optimal clinical results when prescribing an APD. Atypical APDs are often more effective than typical APDs in treating negative symptoms, cognitive impairment, and mood symptoms as well as reducing the risk for suicide and decreasing aggression. This applies not only to those diagnosed with schizophrenia or schizoaffective disorder but also to bipolar disorder, major depression, and other psychiatric diagnoses. The greater advantage of an atypical APD is not evident in all patients for every atypical APD due, in part, to individual differences in genetic and epigenetic endowment and differences in the pharmacology of the atypical APDs, their mode of action being far more complex than that of the typical APDs. A common misconception is that among the atypical APDs, only clozapine is effective for reducing psychosis in treatment-resistant schizophrenia. Aripiprazole, lurasidone, olanzapine, and risperidone also can be more effective than typical APDs for treatment-resistant schizophrenia; clozapine is uniquely indicated for reducing the risk for suicide. The ability of the atypical APDs to improve cognition and negative symptoms in some patients together with lower propensity to cause tardive dyskinesia (an underappreciated advantage) leads to better overall outcomes. These advantages of the atypical APDs in efficacy and safety are due, in part, to initiation of synaptic plasticity via direct and indirect effects of the atypical APDs on a variety of proteins, especially G proteins, and release of neurotrophins (e.g., brain-derived neurotrophic factor). The typical APDs beneficial effects on psychosis are mainly the result of D receptor blockade, which can be associated with serious side effects and lack of tolerability.
抗精神病药物（APDs）具有以下作用的观念：1）有效治疗妄想和幻觉（阳性症状）；2）典型和非典型抗精神病药物在引起锥体外系副作用的能力上存在差异；3）其作为抗精神病药物的疗效归因于多巴胺D受体阻断，这些都是过时的概念，会妨碍临床医生在开具抗精神病药物处方时获得最佳临床效果。非典型抗精神病药物在治疗阴性症状、认知障碍和情绪症状以及降低自杀风险和减少攻击行为方面通常比典型抗精神病药物更有效。这不仅适用于被诊断为精神分裂症或分裂情感性障碍的患者，也适用于双相情感障碍、重度抑郁症和其他精神疾病诊断。非典型抗精神病药物的更大优势并非在所有患者中对每种非典型抗精神病药物都明显，部分原因是遗传和表观遗传禀赋的个体差异以及非典型抗精神病药物药理学的差异，其作用方式远比典型抗精神病药物复杂。一个常见的误解是，在非典型抗精神病药物中，只有氯氮平对难治性精神分裂症的精神病性症状有疗效。阿立哌唑、鲁拉西酮、奥氮平和利培酮对难治性精神分裂症也可能比典型抗精神病药物更有效；氯氮平在降低自杀风险方面具有独特的指征。非典型抗精神病药物在一些患者中改善认知和阴性症状的能力以及导致迟发性运动障碍的倾向较低（这是一个未被充分认识的优势）会带来更好的总体结果。非典型抗精神病药物在疗效和安全性方面的这些优势部分归因于非典型抗精神病药物通过对多种蛋白质（尤其是G蛋白）的直接和间接作用引发突触可塑性以及神经营养因子（如脑源性神经营养因子）的释放。典型抗精神病药物对精神病的有益作用主要是D受体阻断的结果，这可能与严重的副作用和耐受性差有关。
