Background Psychotherapy is the treatment of choice for patients with anorexia nervosa, although evidence of efficacy is weak. The Anorexia Nervosa Treatment of OutPatients (ANTOP) study aimed to assess the efficacy and safety of two manual-based outpatient treatments for anorexia nervosa—focal psychodynamic therapy and enhanced cognitive behaviour therapy—versus optimised treatment as usual. Methods The ANTOP study is a multicentre, randomised controlled efficacy trial in adults with anorexia nervosa. We recruited patients from ten university hospitals in Germany. Participants were randomly allocated to 10 months of treatment with either focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual (including outpatient psychotherapy and structured care from a family doctor). The primary outcome was weight gain, measured as increased body-mass index (BMI) at the end of treatment. A key secondary outcome was rate of recovery (based on a combination of weight gain and eating disorder-specific psychopathology). Analysis was by intention to treat. This trial is registered at http://isrctn.org, number ISRCTN72809357. Findings Of 727 adults screened for inclusion, 242 underwent randomisation: 80 to focal psychodynamic therapy, 80 to enhanced cognitive behaviour therapy, and 82 to optimised treatment as usual. At the end of treatment, 54 patients (22%) were lost to follow-up, and at 12-month follow-up a total of 73 (30%) had dropped out. At the end of treatment, BMI had increased in all study groups (focal psychodynamic therapy 0·73 kg/m2, enhanced cognitive behaviour therapy 0·93 kg/m2, optimised treatment as usual 0·69 kg/m2); no differences were noted between groups (mean difference between focal psychodynamic therapy and enhanced cognitive behaviour therapy −0·45, 95% CI −0·96 to 0·07; focal psychodynamic therapy vs optimised treatment as usual −0·14, −0·68 to 0·39; enhanced cognitive behaviour therapy vs optimised treatment as usual −0·30, −0·22 to 0·83). At 12-month follow-up, the mean gain in BMI had risen further (1·64 kg/m2, 1·30 kg/m2, and 1·22 kg/m2, respectively), but no differences between groups were recorded (0·10, −0·56 to 0·76; 0·25, −0·45 to 0·95; 0·15, −0·54 to 0·83, respectively). No serious adverse events attributable to weight loss or trial participation were recorded. Interpretation Optimised treatment as usual, combining psychotherapy and structured care from a family doctor, should be regarded as solid baseline treatment for adult outpatients with anorexia nervosa. Focal psychodynamic therapy proved advantageous in terms of recovery at 12-month follow-up, and enhanced cognitive behaviour therapy was more effective with respect to speed of weight gain and improvements in eating disorder psychopathology. Long-term outcome data will be helpful to further adapt and improve these novel manual-based treatment approaches. Funding German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), German Eating Disorders Diagnostic and Treatment Network (EDNET).

Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in outpatients with anorexia nervosa (ANTOP study): randomised controlled trial