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.

中文翻译：

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抗抑郁药、抗精神病药及其组合在精神病性抑郁症维持治疗中的现实有效性。来自两个全国队列的受试者内分析的证据


精神病性抑郁症（PD）是一种严重的精神障碍，会导致功能障碍和高自杀风险，但对其维持治疗中使用的药物的相对有效性知之甚少。本研究的目的是调查特定抗精神病药和抗抑郁药及其组合对常规护理中的帕金森病患者住院精神科住院风险的比较效果。从芬兰（2000-2018 年）和瑞典（2006-2021 年）全国住院护理、专科门诊护理、因病缺勤和残疾养老金登记册中确定了首次诊断为 PD 的 16-65 岁患者。主要暴露是特定的抗精神病药物和抗抑郁药物，主要结果指标是精神病住院治疗，作为严重复发的标志。通过个体内设计评估与使用药物与不使用药物期间相关的住院风险（表示为调整后的风险比，aHR），使用每个个体作为他/她自己的对照，并使用分层 Cox 模型进行分析。首先分别对两个国家队列进行分析，然后使用固定效应荟萃分析进行合并。芬兰队列包括 19,330 人（平均年龄：39.8±14.7 岁；57.9% 女性），瑞典队列包括 13,684 人（平均年龄：41.3±14.0 岁；53.5% 女性）。与不使用抗抑郁药相比，与复发风险降低相关的个体抗抑郁药包括安非他酮（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=0.73，95% CI：0.63-0.96）。 =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）与不使用抗精神病药物相比，复发风险降低相关。在单一疗法中，与不使用两种抗抑郁药相比，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相关和抗精神病药。在抗抑郁药-抗精神病药联合用药的探索性分析中，发现阿米替林-奥氮平（aHR=0.45，95% CI：0.28-0.71）、舍曲林-喹硫平（aHR=0.79，95% CI：0.67-0.93）可降低复发风险。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的比较。苯二氮卓类药物及相关药物（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 维持治疗中，安非他酮、沃替西汀、文拉法辛、任何 LAI、氯氮平以及只有少数特定的抗抑郁抗精神病药物组合与复发风险降低相关。这些发现对目前治疗指南建议将抗精神病药与抗抑郁药（没有进一步说明）联合作为 PD 标准治疗的建议提出了挑战。