Background

Anorexia nervosa is a serious illness leading to substantial morbidity and mortality. The Anorexia Nervosa Treatment of Outpatients (ANTOP) study is the largest randomised controlled trial (RCT) globally that uses psychotherapy in outpatients with anorexia nervosa. In this Article, we report the results of the 5-year follow-up.

Methods

The ANTOP study is an open-label, multicentre RCT involving 242 adult female outpatients with anorexia nervosa. Participants were recruited from ten university hospitals in Germany, had to be aged at least 18 years and female, and have a diagnosis of anorexia nervosa with a body-mass index (BMI) of 15·0–18·5 kg/m². Participants were randomly allocated (1:1:1) to 10 months of treatment with focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual; complete masking of the participants was not possible. The mean duration of the follow-up was 5·96 years (SD 0·2) after randomisation. The primary outcome was change in BMI from baseline at the end of treatment; here, we present the change in BMI from baseline to the 5-year follow-up, using an intention-to-treat approach with a mixed model for repeated measurements. Groups were also compared according to global outcome (based on the combination of BMI and measures of anorexia severity), eating pathology (based on the Eating Disorder Inventory 2), and other secondary mental health outcomes. We did a linear regression analysis to identify the predictors of BMI at follow-up.

Findings

Between May, 2007, and June, 2009, we screened 727 patients for eligibility; at baseline, 242 patients with a mean BMI of 16·7 kg/m² (SD 1·0) were included and randomly allocated to 10 months of treatment with focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual. 154 (64%) of 242 patients completed the 5-year follow-up assessment (53 [66%] of 80 in the focal psychodynamic therapy group, 55 [69%] of 80 in the enhanced cognitive behaviour therapy group, and 46 [56%] of 82 in the optimised treatment-as-usual group), with a mean age of 32·4 years; all reported their ethnicity as White. At the 5-year follow-up, there was an improvement in mean BMI, eating pathology, and global outcome in all treatment groups with no significant differences between treatment groups. Estimated mean BMI was: 18·64 kg/m² (95% CI 18·07–19·21) in the focal psychodynamic therapy group (with an estimated mean BMI gain from baseline to 5-year follow-up of 1·91 kg/m² [1·34–2·48]); 18·70 kg/m² (18·15–19·25) in the enhanced cognitive behaviour therapy group (with an estimated mean BMI gain of 1·98 kg/m² [1·43–2·53]); and 18·99 kg/m² (18·39–19·59) in the optimised treatment-as-usual group (with an estimated mean BMI gain of 2·26 kg/m² [1·67–2·86]). There were no significant differences between treatment groups regarding BMI at the 5-year follow-up; the estimated difference was –0·06 (−0·85 to 0·73) between the focal psychodynamic therapy and enhanced cognitive behaviour therapy groups; –0·35 (−1·18 to 0·47) between the focal psychodynamic therapy and optimised treatment-as-usual groups; and –0·29 (−1·10 to 0·52) between the enhanced cognitive behaviour therapy and optimised treatment-as-usual groups. On the basis of observed data, global outcome at the 5-year follow-up showed 41% (33–49) full recoveries, 41% (33–49) partial recoveries, and 18% (12–24) with full-syndrome anorexia nervosa. One patient initially treated in the enhanced cognitive behaviour therapy group died by suicide between the 1-year and 5-year follow-up. BMI at the 5-year follow-up was predicted by BMI at baseline (p=0·0021), illness duration (p=0·0004), and depression at baseline (p=0·012).

Interpretation

The long-term results of the ANTOP trial confirm the improvement in BMI of patients with anorexia nervosa in all groups; however, a substantial proportion of patients had a poor global outcome. The predictors for the long-term course of anorexia nervosa in our ANTOP study show that we need to treat patients with anorexia nervosa at an earlier stage of the disease, with a clear focus on weight gain and considering other comorbidities (especially depression).

Funding

German Federal Ministry of Education and Research.

中文翻译：

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神经性厌食症女性门诊患者的局部心理动力学治疗、认知行为治疗和优化治疗（ANTOP 研究）：德国一项随机对照试验的 5 年随访

背景

神经性厌食症是一种导致大量发病率和死亡率的严重疾病。门诊神经性厌食症治疗 (ANTOP) 研究是全球最大的随机对照试验 (RCT)，该试验在神经性厌食症门诊患者中使用心理治疗。在本文中，我们报告了 5 年随访的结果。

方法

ANTOP 研究是一项开放标签、多中心 RCT，涉及 242 名患有神经性厌食症的成年女性门诊患者。参与者来自德国的十所大学医院，年龄至少为 18 岁，女性，诊断为神经性厌食症，体重指数 (BMI) 为 15·0–18·5 kg/m ². 参与者被随机分配 (1:1:1) 到 10 个月的局部心理动力学治疗、增强认知行为治疗或像往常一样的优化治疗；不可能完全掩盖参与者。随机分组后的平均随访时间为 5·96 年 (SD 0·2)。主要结果是治疗结束时 BMI 相对于基线的变化；在这里，我们使用意向治疗方法和混合模型进行重复测量，展示了 BMI 从基线到 5 年随访的变化。还根据总体结果（基于 BMI 和厌食严重程度测量的组合）、饮食病理学（基于饮食失调量表 2）和其他次要心理健康结果对各组进行了比较。我们进行了线性回归分析以确定随访时 BMI 的预测因子。

发现

从 2007 年 5 月到 2009 年 6 月，我们筛选了 727 名患者的资格；基线时，242 名患者的平均 BMI 为 16·7 kg/m ²(SD 1·0) 被纳入并随机分配至 10 个月的局部心理动力学治疗、增强认知行为治疗或常规优化治疗。242 名患者中的 154 名（64%）完成了 5 年的随访评估（焦点心理动力学治疗组 80 名患者中的 53 名 [66%]，增强认知行为治疗组 80 名患者中的 55 名 [69%]，以及 46 [ 56%] 优化常规治疗组 82 人），平均年龄 32·4 岁；所有人都将他们的种族报告为白人。在 5 年的随访中，所有治疗组的平均 BMI、饮食病理学和整体结果都有所改善，治疗组之间没有显着差异。估计的平均 BMI 为：18·64 kg/m ²(95% CI 18·07–19·21) 焦点心理动力学治疗组（估计从基线到 5 年随访的平均 BMI 增益为 1·91 kg/m ² [1·34–2·48 ]); 增强认知行为治疗组18·70 kg/m ² (18·15–19·25)（估计平均 BMI 增加 1·98 kg/m ² [1·43–2·53]）；和 18·99 kg/m ² (18·39–19·59) 在优化的常规治疗组（估计平均 BMI 增加 2·26 kg/m ²[1·67–2·86]）。在 5 年的随访中，治疗组之间的 BMI 没有显着差异；局部心理动力学治疗组和增强认知行为治疗组之间的估计差异为 –0·06（-0·85 至 0·73）；–0·35（-1·18 到 0·47）在焦点心理动力学治疗和优化治疗照常组之间；和–0·29（-1·10 到 0·52）在增强的认知行为疗法和优化的常规治疗组之间。根据观察到的数据，5 年随访的全球结果显示 41% (33-49) 完全康复，41% (33-49) 部分康复，18% (12-24) 完全康复神经性厌食症。最初在增强认知行为治疗组接受治疗的一名患者在 1 年和 5 年的随访期间死于自杀。

解释

ANTOP 试验的长期结果证实了所有组中神经性厌食症患者 BMI 的改善；然而，很大一部分患者的全球预后不佳。在我们的 ANTOP 研究中，神经性厌食症长期病程的预测因子表明，我们需要在疾病的早期阶段治疗神经性厌食症患者，明确关注体重增加并考虑其他合并症（尤其是抑郁症）。

资金

德国联邦教育和研究部。