Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China.
National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.
Psychiatry Clin Neurosci. 2023 Sep;77(9):486-496. doi: 10.1111/pcn.13567. Epub 2023 Jun 14.
This study identified discrepant therapeutic outcomes of antipsychotics.
A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables.
In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (β = -2.17); ziprasidone related to higher risk of increased QT interval (β range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort.
Future precision medicine should focus on personalized side-effects.
本研究旨在确定抗精神病药物治疗效果的差异。
共纳入 5191 例精神分裂症患者，其中 3030 例为发现队列，1395 例为验证队列，766 例为多祖验证队列。进行抗精神病药物治疗效果广泛关联扫描。抗精神病药物的类型（一种抗精神病药物与其他抗精神病药物）为因变量，疗效和安全性等治疗效果为自变量。
在发现队列中，奥氮平与体重增加（AIWG）、肝功能障碍、镇静、血脂升高的风险增加（OR：2.21-2.86）和锥体外系综合征（EPS）的风险降低（OR：0.14-0.46）相关；利培酮与高催乳素血症的风险增加（OR：12.45-20.53）相关；喹硫平与镇静（OR：1.73）、心悸（OR：2.87）、血脂升高（OR：1.69）的风险增加、低催乳素血症的风险增加（OR：0.09-0.11）和 EPS 的风险降低（OR：0.15-0.44）相关；阿立哌唑与催乳素血症（OR：0.09-0.14）、AIWG（OR：0.44）、镇静（OR：0.33-0.47）和 QTc 延长（β：-2.17）的风险降低相关；齐拉西酮与 QT 间期延长（β范围：3.11-3.22）、恶心（OR：3.22-3.91）、AIWG 风险增加（OR：0.27-0.46）、肝功能障碍（OR：0.41-0.38）和血脂升高（OR：0.41-0.55）相关；氟哌啶醇与 EPS（OR：2.64-6.29）、高催乳素血症（OR：5.45-9.44）和流涎（OR：3.50-3.68）的风险增加相关；奋乃静与 EPS（OR：1.89-2.54）的风险增加相关。在验证队列中，奥氮平和阿立哌唑治疗的肝功能障碍风险增加得到了证实，阿立哌唑治疗的催乳素血症风险降低也得到了证实，而在多祖验证队列中，奥氮平和利培酮治疗的 AIWG 风险增加和利培酮治疗的催乳素血症风险增加也得到了证实。
未来的精准医学应侧重于个性化的副作用。
