We compared the changes in weight (kg) and body mass index (BMI) (kg/m2) in 52 hospitalized adolescents between baseline and after 12 weeks of monotherapy with either (i) olanzapine (OLZ) orally disintegrating tablets (ODT) (N = 16; 16.6 mg/day ± 4.4 [SD]), or (ii) OLZ standard oral tablets (SOT) (N = 10; 18.0 mg/day ± 4.2), or (iii) risperidone (N = 26; 2.8 mg/day ± 1.2). Significantly greater increases in mean weight and BMI were observed in the patients treated with OLZ SOT (8.9 ± 5.1 [SD] kg; 1.9 ± 0.6 kg/m2, respectively) than in those with ODT (3.0 ± 2.1 kg; 1.1 ± 0.8 kg/m2). Similarly, OLZ ODT treatment was associated with significantly greater increases in weight and BMI than risperidone (1.0 ± 1.8 kg; 0.4 ± 0.7 kg/m2). These findings suggest that adolescents gain less weight with OLZ ODT than OLZ SOT, possibly because the former formulation shortens the time of interaction with digestive serotonin receptors mediating satiety.