Off-label treatment of a 17-year-old female patient with anorexia nervosa (AN), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and non-suicidal self-injury (NSSI) with human recombinant leptin (metreleptin) for two dosing periods of 15 and seven days was associated with self- and clinician-rated improvements of eating disorder related psychopathology, OCD, depression, and NSSI. These intermittent improvements occurred despite the patient having high endogenous serum leptin levels ranging up to the 99th centile adjusted for sex, Tanner stage and body mass index (BMI; kg/m²) upon initiation of dosing. The results further extend the hypothesized effects of metreleptin on AN and comorbid psychopathology to patients with adjusted leptin levels in the normal to high range. We hypothesize that for unknown reasons the clinical symptomatology of a subgroup of patients with AN persists despite attainment of endogenous leptin levels well above those characteristic of the state of starvation, potentially entailing a prolonged entrapment in the eating disorder. An insight into the mechanisms underlying this distinct type of leptin resistance may help to promote recovery of such affected patients. Placebo controlled randomized clinical trials are required to assess if and to what extent short and medium term metreleptin treatment indeed improves recovery.
Keywords: Anorexia nervosa; Antidepressant; Hyperleptinemia; Hypoleptinemia; Leptin; Starvation.
© 2025. The Author(s).