Improvements in sleep, weight, and eating-disorder symptoms following off-label leptin treatment in an adolescent with chronic anorexia nervosa and insomnia: a case report

Abstract

We report off-label administration of human recombinant leptin (metreleptin) over a 12-day period in a 17-year-old female adolescent with chronic anorexia nervosa (AN) and clinically significant insomnia. Two observation windows are distinguished throughout: a short-term window between day 1 (pre) and day 12 (post) of dosing, and a longer-term window between day 12 and the two-month follow-up (d + 60), capturing both changes temporally associated with leptin administration and the course of continued weight gain after the end of dosing. Over the short-term window the clinical course comprised a modest weight gain (BMI 15.4 → 16.2 kg/m²), a marked reduction in eating-disorder cognitions and compulsive exercise, attenuation of starvation-associated motor hyperactivity, and changes in objective sleep architecture (more N3 sleep, less wake after sleep onset). In this window, broader cognitive-affective and depressive symptom dimensions remained largely unchanged, and subjective insomnia did not yet improve. Over the longer-term window the course comprised continued substantial weight gain (BMI 18.3 kg/m² at d + 60), a marked drop in subjective insomnia, partial normalisation of circadian rhythm parameters in nonparametric analysis, and a transient increase in broader cognitive-affective symptoms. As a single retrospective case observation, the findings are hypothesis-generating and cannot be disentangled from concurrent weight gain and inpatient treatment. Anorexia nervosa is a serious illness in which a person eats too little and loses a dangerous amount of weight. It is often very hard to treat, and many people with the illness also have problems with sleep. Scientists think that the hormone leptin, which the body makes in fat tissue, may play a part. People who have lost a lot of weight have very little leptin, and low leptin levels may be linked both to the restless, driven behaviour seen in the illness and to poor sleep. In this report we describe the treatment of one 17-year-old girl who had been seriously ill with anorexia nervosa for a long time and also had difficulty sleeping. As an experimental treatment, and with the agreement of the patient and her parents, she was treated with metreleptin (a manufactured form of leptin) as a daily injection for 12 days, alongside her usual hospital care. We followed her closely during the 12 days and again about two months later, measuring her weight, her eating-disorder symptoms, her physical restlessness and her sleep, including with overnight sleep recordings and a movement sensor worn on the wrist. During the 12 days of treatment she gained some weight, her eating-disorder thoughts and her urge to exercise lessened, she became less physically restless, and the deep, restful stage of her sleep increased. Her own sense of having insomnia did not improve straight away, but by the two-month follow-up it had clearly improved, and she had continued to gain weight. Some other symptoms, such as low mood, briefly became more noticeable again as she gained weight. The treatment was generally well tolerated, with no side effects reported. Because this is a single case and the patient was also receiving normal treatment and gaining weight at the same time, we cannot prove that leptin caused these improvements. The findings should be seen as a starting point for further research rather than as proof that the treatment works. Carefully designed studies in larger groups are needed to find out whether leptin can genuinely help sleep and other symptoms in people with anorexia nervosa.