Supplementary file 4_The antipsychotics functional index (AFI) in schizophrenia.docx

Schizophrenia can lead to significant and long-lasting deficits in patient functionality. The present study proposes a theoretical index that predicts the ability of an antipsychotic to improve the functionality of patients with schizophrenia. An advantage of this theoretical index is that it directly compares 29 first- and second-generation antipsychotics. This theoretical index, named the Antipsychotics Functional Index (AFI), was constructed considering factors such as pharmacodynamics, pharmacokinetics, pharmaceutical form, ease of administration, and safety aspects. A good antipsychotic ranking based on the proposed index results from combining the partial dopaminergic agonist mechanism and a lower frequency of administration. The top-ranked antipsychotic is aripiprazole long-acting injection (LAI) administered every 2 months, 6 weeks, or 1 month, which is the only antipsychotic D2 partial agonist with an LAI formulation. It is followed by paliperidone LAI administered every 6 months. This antipsychotic has the least frequent administration schedule. According to the AFI, the most favorable antipsychotics for functionality are generally second-generation LAI antipsychotics. The D2 partial agonist mechanism has a pharmacodynamic advantage. Based on this functionality index, psychiatrists could select the most suitable antipsychotic for each patient, with the ultimate goal of helping the patient achieve their maximum potential.

精神分裂症可导致患者出现显著且持久的功能缺损。本研究提出一项理论性指标，用于预测抗精神病药物改善精神分裂症患者功能的能力。该理论指标的优势在于可直接对比29种第一代与第二代抗精神病药物。本理论指标被命名为抗精神病药物功能指数（Antipsychotics Functional Index，AFI），其构建综合考量了药效动力学、药代动力学、剂型、给药便利性及安全性等多方面因素。基于该指标得到的优质抗精神病药物排序，需结合多巴胺D2受体部分激动机制与更低的给药频率共同确定。排名最高的抗精神病药物为每2个月、6周或1个月给药一次的阿立哌唑长效注射剂（long-acting injection，LAI），这是目前唯一一款采用长效注射剂剂型的多巴胺D2受体部分激动类抗精神病药物。紧随其后的是每6个月给药一次的帕利哌酮长效注射剂（LAI），该药物的给药间隔最长。根据AFI指标，对功能改善最具优势的抗精神病药物通常为第二代长效注射剂类抗精神病药物。多巴胺D2受体部分激动机制具备药效动力学层面的优势。借助这一功能评估指标，精神科医师可为每位患者遴选最适配的抗精神病药物，最终目标是帮助患者实现其最大潜能。