Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland (Taipale, Tanskanen, Tiihonen); Department of Clinical Neuroscience, Karolinska Institutet, and Center for Psychiatry Research, Stockholm City Council, Stockholm (Taipale, Tanskanen, Tiihonen); School of Pharmacy, University of Eastern Finland, Kuopio, Finland (Taipale); Population Health Unit, Finnish Institute for Health and Welfare, Helsinki (Tanskanen); Neuroscience Center, University of Helsinki, Helsinki (Tiihonen).
Am J Psychiatry. 2023 May 1;180(5):377-385. doi: 10.1176/appi.ajp.20220446. Epub 2023 Mar 22.
The authors sought to study the safety of antipsychotic polypharmacy compared with monotherapy in specific dosage categories.
Patients with schizophrenia (N=61,889; median follow-up, 14.8 years [IQR=7.4-22.0]) were identified from the Finnish nationwide inpatient care register and followed up over the period 1996-2017. Antipsychotic polypharmacy was compared with monotherapy in seven dosage categories (<0.4, 0.4-<0.6, 0.6-<0.9, 0.9-<1.1, 1.1-<1.4, 1.4-<1.6, and ≥1.6 defined daily doses [DDDs] per day) in terms of risk of severe physical morbidity, indicated by nonpsychiatric and cardiovascular hospitalizations (adjusted hazard ratio). Within-individual analysis was used in an effort to eliminate selection bias.
The mean age of the cohort was 46.7 years (SD=16.0), and 50.3% (N=31,104) were men. Among patients who had used both monotherapy and polypharmacy, the risk of nonpsychiatric hospitalization was significantly lower during polypharmacy use at all total dosage categories above 1.1 DDDs/day with differences up to -13% than during monotherapy use of the same dosage category (for 1.1-<1.4 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.87-0.95; for 1.4-<1.6 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.86-0.96; and for ≥1.6 DDDs/day, adjusted hazard ratio=0.87, 95% CI=0.84-0.89). The risk of cardiovascular hospitalization was significantly lower for polypharmacy at the highest total dosage category (-18%, adjusted hazard ratio=0.82, 95% CI=0.72-0.94). The results from the comparisons between monotherapy and no use and between polypharmacy and no use were in line with the primary comparison of polypharmacy and monotherapy within the same individual. Comparison of any polypharmacy use with any monotherapy use showed no significant difference for nonpsychiatric or cardiovascular hospitalization.
The results show that antipsychotic monotherapy is not associated with a lower risk of hospitalization for severe physical health problems when compared with antipsychotic polypharmacy. Treatment guidelines should not encourage use of monotherapy instead of antipsychotic polypharmacy without any existing evidence on the safety issues.
作者旨在研究特定剂量类别下的抗精神病药联合用药与单药治疗的安全性。
从芬兰全国住院患者登记处中确定了（N=61889；中位随访时间，14.8 年[IQR=7.4-22.0]）患有精神分裂症的患者，并在 1996-2017 年期间对其进行了随访。在七个剂量类别（<0.4、0.4-<0.6、0.6-<0.9、0.9-<1.1、1.1-<1.4、1.4-<1.6 和≥1.6 定义日剂量[DDD]）中，将联合用药与单药治疗进行比较，根据非精神科和心血管住院情况（调整后的危害比）评估严重躯体发病率的风险。采用个体内分析以消除选择偏倚。
队列的平均年龄为 46.7 岁（SD=16.0），50.3%（N=31104）为男性。在使用过单药和联合用药的患者中，在所有总剂量类别中，联合用药的非精神科住院风险明显低于单药治疗相同剂量类别，差异最高可达-13%（1.1-<1.4 DDD/天，调整后的危害比=0.91，95%CI=0.87-0.95；1.4-<1.6 DDD/天，调整后的危害比=0.91，95%CI=0.86-0.96；≥1.6 DDD/天，调整后的危害比=0.87，95%CI=0.84-0.89）。在最高总剂量类别中，联合用药的心血管住院风险显著降低（-18%，调整后的危害比=0.82，95%CI=0.72-0.94）。与单药治疗和未使用药物的比较结果以及与未使用药物的联合用药比较结果均与同一个体中单药治疗与联合用药的主要比较结果一致。与任何单药治疗相比，任何联合用药治疗的非精神科或心血管住院风险均无显著差异。
结果表明，与抗精神病药联合用药相比，抗精神病药单药治疗并不会降低严重躯体健康问题的住院风险。在没有关于安全性问题的现有证据的情况下，治疗指南不应鼓励在没有任何证据的情况下使用单药治疗代替抗精神病药联合用药。
