Wolfgang Herzog, Beate Wild, Katrin E Giel, Florian Junne, Hans-Christoph

Friederich, Gaby Resmark, Martin Teufel, Dieter Schellberg, Martina de Zwaan,

Andreas Dinkel, Stephan Herpertz, Markus Burgmer, Bernd Löwe, Almut Zeeck, Jörn von
Wietersheim, Sefik Tagay, Carmen Schade-Brittinger, Henning Schauenburg, Ulrike
Schmidt, Stephan Zipfel,
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,
The Lancet Psychiatry,
Volume 9, Issue 4,
2022,
Pages 280-290,
ISSN 2215-0366,
https://doi.org/10.1016/S2215-0366(22)00028-1.
(https://www.sciencedirect.com/science/article/pii/S2215036622000281)
Abstract: 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.