Elsevier

The Lancet Psychiatry

Volume 9, Issue 4, April 2022, Pages 280-290
The Lancet Psychiatry

Articles
Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in female outpatients with anorexia nervosa (ANTOP study): 5-year follow-up of a randomised controlled trial in Germany

https://doi.org/10.1016/S2215-0366(22)00028-1Get rights and content

Summary

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.

Introduction

Anorexia nervosa is a serious illness leading to substantial morbidity and mortality as a result of both malnutrition and suicide.1 Given the enduring course of anorexia nervosa and the suffering of patients and families, several groups did long-term, naturalistic, course-of-illness studies,2, 3, 4 which reported a high standardised mortality ratio5 (of more than 5·8) and severe somatic and mental comorbidities.6 A review of 119 patient series published in 2002 established the 4–10-year global outcome for 2132 adult patients with anorexia nervosa; they found 47% full recoveries, 34% intermediate recoveries, and 20% enduring courses.7 Unfortunately, most of the studies included in this review had methodological limitations, such as retrospective study design, no reporting of study protocols, small sample sizes, selection bias, no control groups, varying follow-up periods, and no standardised interviews or questionnaires. Since then, at least 35 randomised controlled trials (RCTs) for the treatment of patients with anorexia nervosa have increased the evidence base,8 of which at least 20 investigated psychotherapeutic treatments.9 Nevertheless, a Cochrane review of these trials could not draw firm conclusions about the effects of specific individual psychological outpatient therapies for adults with anorexia nervosa and called for larger RCTs with longer treatment duration and follow-up.10

A high-quality systematic review and network meta-analysis11 of psychological interventions for adult outpatients with anorexia nervosa, published in 2021,12 could identify only 13 RCTs suitable for inclusion (1047 patients in total), and only two of them with treatment groups of more than 50 patients.13, 14 The analysis showed that available outpatient treatments for anorexia nervosa were associated with modest improvements and that “no clear evidence currently supports the superiority or inferiority of any specific manualised psychotherapeutic intervention that is indicated as first-line treatment in international clinical guidelines over treatment as usual after 1 year”.12 This statement indirectly highlights the importance of the control condition in RCTs of patients with anorexia nervosa. For ethical reasons, untreated control groups are not possible in anorexia treatment studies and, according to the respective health-care system, treatment-as-usual conditions differ widely. Therefore, treatment as usual has to be described accurately and put into context in each RCT.

The few RCTs in adult outpatients with anorexia nervosa report follow-up data for only small samples15 or include a follow-up period of only 1 year.13, 14, 16 This period seems comparatively short, as follow-up studies after inpatient treatment for anorexia nervosa have shown that changes in the course of the disease cover longer periods of time.4, 6, 7, 17 Schmidt and colleagues published a 1-year follow-up of the MOSAIC trial,14 which compared the Maudsley Model for Anorexia Nervosa Treatment for Adults (MANTRA) with specialist supportive clinical management (SSCM) in 142 outpatients with broadly defined anorexia nervosa. Based on a participation rate of 73·2%, results showed that both groups had improved in terms of mean body-mass index (BMI) and eating disorder symptoms, with no differences between groups. Similarly, Byrne and colleagues, in a 1-year follow-up of an RCT comparing MANTRA, SSCM, and cognitive behaviour therapy,16 reported no differences between treatment groups regarding weight gain and remission, on the basis of a retention rate of 52%. However, although anorexia nervosa frequently has a severe and enduring course, there has been a dearth of systematically conducted long-term follow-up reports from RCTs in people with anorexia nervosa.18

The multicentre Anorexia Nervosa Treatment of Outpatients (ANTOP) RCT13, 19, 20, 21, 22 is to date the largest psychotherapy RCT in adult outpatients with anorexia nervosa worldwide.12 The study compared two psychotherapeutic outpatient treatments for adults with anorexia nervosa—focal psychodynamic therapy or enhanced cognitive behaviour therapy—with an optimised treatment-as-usual approach. The optimised treatment-as-usual group received psychotherapy according to the German psychotherapy guidelines, enhanced by monitoring by the family doctor and the support of the study centre. Results of the RCT indicated that focal psychodynamic therapy was more advantageous in terms of recovery at 1-year follow-up and that enhanced cognitive behaviour therapy was more effective in regard to speed of weight gain and improvements in eating disorder psychopathology. A health-economic analysis showed that, although differences in costs at the 1-year follow-up were not significant, the absolute costs of inpatient treatment and the percentage of patients who required inpatient treatment were considerably lower in both intervention groups.21

The aim of the 5-year follow-up of the ANTOP study was, first, to evaluate the long-term outcomes of a well described and fairly homogeneous sample of adult patients with anorexia nervosa and, second, to examine whether the treatment advantages found at the 1-year follow-up would persist more than 4 years later.

Section snippets

Study design and participants

Detailed methods have been previously published.13 ANTOP was an open-label, multicentre RCT in adult outpatients with anorexia nervosa, recruited from ten university departments of psychosomatic medicine and psychotherapy in Germany. The 5-year follow-up was conducted between March, 2013, and May, 2015. For patients to be included at baseline, they had to be aged at least 18 years, be female, have a diagnosis of anorexia nervosa or subsyndromal anorexia nervosa, and have a BMI of 15·0–18·5 kg/m2

Results

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. The 5-year follow-up for this analysis was completed on May 31, 2015. The follow-up attrition rate did not differ between the three groups (27 [34%] of 80 participants in the focal

Discussion

To date, there have been few long-term follow-up data from RCTs, not only in people with anorexia nervosa but in people with any mental disorder. Results of this 5-year follow-up are meaningful because the highest probability of recovery in individuals with anorexia nervosa was observed during the first 6 years after initiation of treatment in a previous study.17 Compared with our 1-year follow-up, we observed further weight gain and an improvement in eating disorder-specific psychopathology in

Data sharing

The data that support the findings of this study are available on request from the corresponding author.

Declaration of interests

We declare no competing interests.

References (38)

  • MM Fichter et al.

    Twelve-year course and outcome predictors of anorexia nervosa

    Int J Eat Disord

    (2006)
  • J Arcelus et al.

    Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies

    Arch Gen Psychiatry

    (2011)
  • W Herzog et al.

    Medical findings and predictors of long-term physical outcome in anorexia nervosa: a prospective, 12-year follow-up study

    Psychol Med

    (1997)
  • HC Steinhausen

    The outcome of anorexia nervosa in the 20th century

    Am J Psychiatry

    (2002)
  • SB Murray et al.

    Treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of randomized controlled trials

    Psychol Med

    (2019)
  • A Zeeck et al.

    Psychotherapeutic treatment for anorexia nervosa: a systematic review and network meta-analysis

    Front Psychiatry

    (2018)
  • PJ Hay et al.

    Individual psychological therapy in the outpatient treatment of adults with anorexia nervosa

    Cochrane Database Syst Rev

    (2015)
  • B Hutton et al.

    The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations

    Ann Intern Med

    (2015)
  • U Schmidt et al.

    Two-year follow-up of the MOSAIC trial: a multicenter randomized controlled trial comparing two psychological treatments in adult outpatients with broadly defined anorexia nervosa

    Int J Eat Disord

    (2016)
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