Characterising the pharmacokinetics of olanzapine in patients with anorexia nervosa (TORPEDO): protocol for a multicentre cross-sectional study.

Abstract

Anorexia nervosa (AN) is a debilitating eating disorder with one of the highest mortality rates of all psychiatric disorders. The lifetime prevalence rates of AN might be up to 4% among females and 0.3% among males. According to a systematic review, the pooled incidence rate of AN in females is 8.8 per 100 000 person-years; 95% CI 7.8 to 9.8. The path towards full recovery is often long and only half of the patients recover completely after 10 years. As part of the treatment of AN, olanzapine is frequently used to reduce severe anxiety, agitation and obsessive compulsions. Due to a dearth of pharmacokinetic studies on olanzapine in this population with altered body composition, and side effects, doctors often dose low out of precaution. These low doses are potentially subtherapeutic and elongate the progression and the treatment. In this study, we aim to research the pharmacokinetics of olanzapine in AN patients to facilitate more adequate dosing strategies in this vulnerable group. Towards precision dosing of olanzapine in anorexia nervosa patient<b>s</b> (TORPEDO) is a multicentre, cross-sectional observational study. It includes patients aged 12-30 years who are being treated with olanzapine for either AN (n=30) or other non-AN psychiatric indications (n=30). The aim is to develop population pharmacokinetic models of patients with AN and those without, in order to compare how AN affects the pharmacokinetics of olanzapine. Olanzapine plasma day-curve will be obtained using capillary micro sampling. In a secondary analysis, we will examine associations between olanzapine pharmacokinetic parameters and clinical outcomes, including treatment effectiveness, extrapyramidal side effects, cardiac abnormalities and metabolic laboratory markers. This study was approved by the Medical Ethics Committee of the Erasmus Medical Center in Rotterdam, the Netherlands (registration number MEC-2022-0687). This ethical approval covers all study sites. Every significant amendment to the protocol will have to be approved by the medical ethics committee. The local feasibility was tested by the medical ethics committee and board of directors of all study sites included in the study. Written informed consent will be obtained from the patients and/or the legal representative(s) before enrolment in the study. Findings will be disseminated through publication in peer-reviewed journals and presentation at national and international conferences. Results will contribute to the evidence base for optimising olanzapine dosing in patients with AN.