Abstract
To examine the hypothesis that normalization of low circulating leptin levels in patients with anorexia nervosa ameliorates hyperactivity, three seriously ill females with hyperactivity were treated off-label with metreleptin (recombinant human leptin) for up to 14 days. Drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased in two patients. Surprisingly, depression improved rapidly in all patients. No serious adverse events occurred. Due to obvious limitations of uncontrolled case series, placebo-controlled clinical trials are mandatory to confirm the observed rapid onset of beneficial effects. Our findings suggest an important role of hypoleptinemia in the mental and behavioral phenotype of anorexia nervosa.