Open AccessMetformin add‐on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness: results from the IMPACT trial
Author(s) -
Correll Christoph U.,
Sikich Linmarie,
Reeves Gloria,
Johnson Jacqueline,
Keeton Courtney,
Spanos Marina,
Kapoor Sandeep,
Bussell Kristin,
Miller Leslie,
Chandrasekhar Tara,
Sheridan Eva M.,
Pirmohamed Sara,
Reinblatt Shauna P.,
Alderman Cheryl,
Scheer Abigail,
Borner Irmgard,
Bethea Terrence C.,
Edwards Sarah,
Hamer Robert M.,
Riddle Mark A.
Publication year - 2020
Publication title -
world psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.51
H-Index - 93
eISSN - 2051-5545
pISSN - 1723-8617
DOI - 10.1002/wps.20714
Subject(s) - medicine , aripiprazole , antipsychotic , overweight , body mass index , bipolar disorder , bipolar i disorder , schizophrenia (object oriented programming) , randomized controlled trial , weight gain , psychiatry , obesity , pediatrics , lithium (medication) , mania , body weight
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.