TORPEDO Will Test Whether Olanzapine Exposure Differs in Anorexia Nervosa
Anorexia nervosa carries a severe mortality burden and remains one of the most difficult psychiatric disorders to treat. In clinical practice, olanzapine is often used to ease severe anxiety, agitation, and obsessive compulsions, yet prescribing in this population has long been shaped by caution rather than pharmacokinetic evidence. Low body mass, altered body composition, and concerns about side effects push clinicians toward conservative dosing. The consequence is clinically important: doses that are too low may fail to deliver adequate exposure, leaving symptoms insufficiently controlled and prolonging an already difficult recovery trajectory.
TORPEDO, a multicentre cross-sectional observational study, is designed to address that gap directly. The study will characterize the pharmacokinetics of olanzapine in patients with anorexia nervosa and compare them with those in patients taking the drug for other psychiatric indications. By doing so, investigators aim to build population pharmacokinetic models that can support more precise dosing in a group where standard prescribing assumptions may not hold.
A Vulnerable Population With Limited Dosing Data
The rationale for the study is anchored in the clinical burden of anorexia nervosa itself. Lifetime prevalence may reach 4% among females and 0.3% among males, and pooled incidence in females has been estimated at 8.8 per 100,000 person-years. Recovery is often prolonged, and complete recovery after 10 years occurs in only about half of patients. Those figures matter because pharmacotherapy in anorexia nervosa is rarely straightforward: nutritional depletion, low weight, and shifts in body composition can alter how drugs distribute and behave in the body.
Olanzapine sits at the center of that uncertainty. Clinicians already use it in anorexia nervosa, but the evidence base for dosing in this setting remains thin. In day-to-day care, the instinct to start low is understandable. In pharmacology terms, though, lower dosing can reduce the chance of achieving exposures needed to influence anxiety, agitation, or rigid obsessive thinking. When the effective concentration is unknown, cautious prescribing can drift into underdosing without any clear warning sign until treatment response stalls.
One sentence captures the clinical problem: subtherapeutic exposure can quietly become the default.
Cross-Sectional Design, Two Clinical Groups, One Drug
TORPEDO is set up as a multicentre observational study involving patients aged 12 to 30 years who are already receiving olanzapine. The protocol includes 30 patients with anorexia nervosa and 30 patients without anorexia nervosa who are taking olanzapine for other psychiatric indications. This parallel structure is important because it allows investigators to compare how the disorder itself may alter drug handling, rather than simply observing olanzapine exposure in a single mixed cohort.
The planned analysis centers on population pharmacokinetic modeling. In practical terms, the study will not rely on a single blood draw or a crude comparison of dose alone. Instead, it will reconstruct drug exposure patterns and estimate how pharmacokinetic parameters differ between the two groups. That design is well suited to a question like this, where body composition and clinical state may affect absorption, distribution, metabolism, or clearance in ways that are not visible from routine prescribing data.
Olanzapine plasma day-curve sampling will be collected using capillary micro sampling. This approach is especially relevant in younger patients and in a population where repeated venous sampling can be burdensome. Sparse, minimally invasive sampling can still support robust pharmacokinetic modeling when it is paired with the right analytic framework. For anorexia nervosa, where distress around procedures can be significant, reducing sampling burden is more than a convenience; it is a feasibility measure that aligns with the realities of care.
Clinical Outcomes Beyond Concentration Alone
The protocol also includes a secondary analysis linking pharmacokinetic parameters with clinically meaningful outcomes. Investigators will examine treatment effectiveness, extrapyramidal side effects, cardiac abnormalities, and metabolic laboratory markers. That broader lens matters because olanzapine is not used in a vacuum. Exposure that is too low may fail to improve symptoms, while exposure that is too high may worsen adverse effects, particularly in patients whose physiology may already be fragile.
Cardiac abnormalities and metabolic markers deserve particular attention in anorexia nervosa. Even before adding antipsychotic therapy, many patients have physiologic vulnerability related to malnutrition. If olanzapine exposure differs substantially in this group, the balance between benefit and harm could shift in ways that standard dosing does not anticipate. Extrapyramidal side effects are also clinically relevant because they can undermine adherence and compound distress in patients already struggling with a difficult psychiatric illness.
The protocol does not claim these relationships are already established. It is designed to measure them.
Ethics, Oversight, and Why the Protocol Matters Now
The study received approval from the Medical Ethics Committee of the Erasmus Medical Center in Rotterdam, with coverage extending to all study sites. Written informed consent will be obtained from patients and/or their legal representatives before enrollment. Any significant protocol amendment will require further ethics approval, and local feasibility has already been assessed by the ethics committee and boards of directors at the participating sites.
That administrative structure is not a minor detail. Research in adolescents and young adults with anorexia nervosa requires careful oversight because the clinical population is medically and psychologically complex, and the study procedures must be proportional to the question being asked. TORPEDO appears built around that balance: enough sampling to answer an important pharmacokinetic question, but with a minimally invasive approach and multicentre coordination to make the work feasible.
The practical endpoint is not abstract. If olanzapine exposure proves to differ meaningfully in anorexia nervosa, clinicians may need dosing strategies tailored to altered physiology rather than relying on cautious low-dose habits that are common but untested. If exposure is not materially different, that result would also be useful, because it would support more confident prescribing and reduce uncertainty around dose escalation.
Results will be disseminated through peer-reviewed publication and presentation at national and international conferences. Until then, the main value of TORPEDO lies in its premise: in a disorder where recovery is slow and treatment options are limited, dosing based on assumption is a poor substitute for measured pharmacokinetic data.