精神病性抑郁症(PD)是一种严重的精神障碍,导致功能障碍和高自杀风险,但是对于维持治疗中使用的药物的相对有效性知之甚少。这项研究的目的是调查特定抗精神病药和抗抑郁药的比较有效性,以及它们的组合,关于常规护理中PD患者精神病住院的风险。从芬兰(2000-2018年)和瑞典(2006-2021年)全国住院护理登记册中确定了16-65岁首次诊断为PD的人。专科门诊护理,疾病缺席,残疾抚恤金。主要暴露于特定的抗精神病药和抗抑郁药,主要结局指标是精神病住院作为严重复发的标志.与使用时间相关的住院风险与不使用药物(表示为调整后的危险比,aHR)是由个人内部设计评估的,使用每个人作为他/她自己的控制,并采用分层Cox模型进行分析。首先分别分析了两个国家队列,然后使用固定效应荟萃分析进行组合。芬兰队列包括19,330人(平均年龄:39.8±14.7岁;57.9%的女性)和瑞典队列13,684人(平均年龄:41.3±14.0岁;53.5%的女性)。与复发风险降低相关的个体抗抑郁药与不使用抗抑郁药是安非他酮(aHR=0.73,95%CI:0.63-0.85),沃替西汀(aHR=0.78,95%CI:0.63-0.96)和文拉法辛(aHR=0.92,95%CI:0.86-0.98)。任何长效注射抗精神病药(LAI)(aHR=0.60,95%CI:0.45-0.80)和氯氮平(aHR=0.72,95%CI:0.57-0.91)与复发风险降低有关不使用抗精神病药。在单一疗法中,只有沃替西汀(aHR=0.67,95%CI:0.47-0.95)和安非他酮(aHR=0.71,95%CI:0.56-0.89)与复发风险显着降低有关。不使用抗抑郁药和抗精神病药。在对抗抑郁药-抗精神病药组合的探索性分析中,阿米替林-奥氮平的复发风险降低(aHR=0.45,95%CI:0.28-0.71),舍曲林-喹硫平(aHR=0.79,95%CI:0.67-0.93)和文拉法辛-喹硫平(aHR=0.82,95%CI:0.73-0.91)与不使用抗抑郁药和抗精神病药。苯二氮卓类药物和相关药物(aHR=1.29,95%CI:1.24-1.34)和米氮平(aHR=1.17,95%CI:1.07-1.29)与复发风险增加相关。这些数据表明,在PD的维持治疗中,安非他酮,沃替西汀,文拉法辛,任何LAI,氯氮平,只有少数特定的抗抑郁药-抗精神病药组合与复发风险降低相关。这些发现挑战了当前治疗指南的建议,即将抗精神病药与抗抑郁药(没有进一步说明)作为PD的标准治疗。
Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.