Olanzapine for young PEople with aNorexia nervosa (OPEN): results of a feasibility study.

Abstract

Background: Despite the availability of evidence-based treatments for anorexia nervosa (AN), remission rates are moderate, and mortality is high. Olanzapine is used as adjunct therapy for AN in case of insufficient response to first-line treatments, even though the evidence is limited. Its effect on eating disorder (ED) psychopathology, its efficacy and tolerability, and its acceptability and adherence rate are unclear.

Methods: We assessed the feasibility of a future definitive trial on olanzapine in young people with AN in an open-label, one-armed feasibility study that aimed to include 55 patients with AN or atypical AN aged 12-24 who gained < 2 kg within at least one month of treatment as usual (TAU) during outpatient, inpatient, or day-care treatment. Time points for assessments were at baseline, 8 weeks, 16 weeks, and 6 or 12 months. We estimated the following planning parameters: Recruitment rate (number of patients who agreed to take olanzapine/number eligible), adherence rate (number adhering to treatment/number recruited) and attrition rate (number completing study assessments/number recruited). In addition, two exploratory effect size parameters were estimated: Mean change in body mass index (BMI) and mean change in ED psychopathology.

Results: Fifty-two people were pre-screened (June 2022 to May 2023; 10 study sites in England). 13 were ineligible at pre-screening . Of the 39  approached, 4 were found ineligible at screening. Of the remaining 35 eligible, 10 declined and 5 did not take part for other reasons. Thus, 20 participants were recruited and started olanzapine (recruitment rate: 20/35 = 57%). 15 out of 20 (75%) continued olanzapine for ≥ 16 weeks, and 13 participants (65%) remained in the trial until follow-up (either 6 or 12 months). Participants experienced, on average, a decrease over time in their Eating Disorder Examination Questionnaire (EDE-Q) Global scores (0.07 per week, N = 20) and an increase in BMI (0.08 kg/m² per week, N = 20) during treatment with olanzapine plus TAU.

Conclusions: Possible reasons for the recruitment difficulties and low adherence rate include the high clinical workload of ED services during the COVID-19 pandemic and the reluctance of patients to agree to take olanzapine under the relatively restricted conditions of a clinical study.

Trial registration: International standard randomised controlled trial register number: ISRCTN80075010. Registration date: 27/04/2022.