Antipsychotics are used for many psychiatric conditions in youth. Although developmentally inappropriate
weight gain and metabolic abnormalities, which are risk factors for premature cardiovascular mortality, are especially frequent in youth, optimal strategies to reduce pediatric antipsychotic-induced
overweight/
obesity are unclear. The Improving Metabolic Parameters in
Antipsychotic Child Treatment (IMPACT) was a randomized, parallel group, 24-week clinical trial which enrolled
overweight/obese, psychiatrically stable youth, aged 8-19 years, with a DSM-IV diagnosis of severe
mental illness (
schizophrenia spectrum
disorder, bipolar spectrum disorder or psychotic depression), at four US universities. All of them had developed substantial
weight gain following treatment with a second-generation
antipsychotic. The centralized, computer-based randomization system assigned participants to unmasked treatment groups:
metformin (MET);
antipsychotic switch (
aripiprazole or, if already exposed to that drug,
perphenazine or
molindone; SWITCH); or continued baseline
antipsychotic (CONTROL). All participants received healthy lifestyle education. The primary outcome was body mass index (BMI) z-score change from baseline, analyzed using estimated least squares means. Altogether, 127 participants were randomized: 49 to MET, 31 to SWITCH, and 47 to CONTROL. BMI z-score decreased significantly with MET (week 24: -0.09±0.03, p=0.002) and SWITCH (week 24: -0.11±0.04, p=0.003), while it increased non-significantly with CONTROL (week 24: +0.04±0.03). On 3-way comparison, BMI z-score changes differed significantly (p=0.001). MET and SWITCH were each superior to CONTROL (p=0.002), with effect sizes of 0.68 and 0.81 respectively, while MET and SWITCH did not differ. More gastrointestinal problems occurred in MET than in SWITCH or CONTROL. The data safety monitoring board closed the
perphenazine-SWITCH arm because 35.2% of subjects discontinued treatment due to psychiatric worsening. These data suggest that pediatric
antipsychotic-related
overweight/
obesity can be reduced by adding
metformin or switching to a lower risk
antipsychotic. Healthy lifestyle education is not sufficient to prevent ongoing BMI z-score increase.