New York Medical College, Valhalla, NY, USA,
CNS Drugs. 2013 Nov;27(11):879-911. doi: 10.1007/s40263-013-0105-7.
Evidence-based medicine (EBM) is a broad concept, but the key elements include the incorporation of clinical judgment (which requires clinical experience) together with relevant scientific evidence while remaining mindful of the individual patient's values and preferences. Using the framework and philosophy of EBM, this systematic review summarizes the pharmacology, efficacy, and tolerability of newly approved oral antipsychotics, including iloperidone, asenapine, and lurasidone, and outlines what is known about agents that are in late-stage clinical development, such as cariprazine, brexpiprazole, zicronapine, bitopertin, and EVP-6124. Potential advantages and disadvantages of these agents over existing antipsychotics are outlined, centered on clinically relevant issues such as the potential for weight gain and metabolic abnormalities, potential association with somnolence/sedation, extra-pyramidal side effects, akathisia, and prolongation of the electrocardiogram (ECG) QT interval, as well as practical issues regarding dosing instructions, titration requirements, and drug-drug interactions. Lurasidone appears to be best in class in terms of minimizing untoward alterations in body weight and metabolic variables. However, iloperidone, asenapine, lurasidone, and cariprazine differ among themselves in terms of on-label dosing frequency (once daily for lurasidone and, presumably, cariprazine versus twice daily for iloperidone and asenapine), the need for initial titration to a therapeutic dose for iloperidone and possibly cariprazine, requirement to be taken sublingually for asenapine, requirement for administration with food for lurasidone, lengthening of the ECG QT interval (greater for iloperidone than for asenapine and no effect observed with lurasidone), and adverse effects such as akathisia (seen with cariprazine, lurasidone, and asenapine but not with iloperidone) and sedation (most notable with asenapine).
循证医学（EBM）是一个广泛的概念，但关键要素包括将临床判断（需要临床经验）与相关科学证据相结合，同时牢记个体患者的价值观和偏好。本系统评价采用循证医学的框架和理念，总结了新近批准的口服抗精神病药物的药理学、疗效和耐受性，包括伊洛哌酮、阿塞那平、鲁拉西酮，并概述了处于临床后期开发阶段的药物的相关信息，如卡利培嗪、布瑞哌唑、齐克隆嗪、比托特嗪和 EVP-6124。围绕可能引起体重增加和代谢异常、与嗜睡/镇静相关的潜在风险、锥体外系副作用、静坐不能和心电图（ECG）QT 间期延长等临床相关问题，以及关于剂量说明、滴定要求和药物相互作用等实际问题，概述了这些药物与现有抗精神病药物相比的潜在优势和劣势。鲁拉西酮在最小化体重和代谢变量不良改变方面似乎是同类最佳。然而，伊洛哌酮、阿塞那平、鲁拉西酮和卡利培嗪在标签剂量频率（鲁拉西酮为每日一次，可能还有卡利培嗪为每日一次，而伊洛哌酮和阿塞那平为每日两次）、伊洛哌酮和可能还有卡利培嗪初始滴定至治疗剂量的需求、阿塞那平需舌下给药、鲁拉西酮需随餐服用、心电图 QT 间期延长（伊洛哌酮大于阿塞那平，鲁拉西酮无影响）以及静坐不能（卡利培嗪、鲁拉西酮和阿塞那平可见，而伊洛哌酮不可见）和镇静（以阿塞那平最为明显）等方面存在差异。
