TY - JOUR
T1 - Metformin add-on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness
T2 - results from the IMPACT trial
AU - Correll, Christoph U.
AU - Sikich, Linmarie
AU - Reeves, Gloria
AU - Johnson, Jacqueline
AU - Keeton, Courtney
AU - Spanos, Marina
AU - Kapoor, Sandeep
AU - Bussell, Kristin
AU - Miller, Leslie
AU - Chandrasekhar, Tara
AU - Sheridan, Eva M.
AU - Pirmohamed, Sara
AU - Reinblatt, Shauna P.
AU - Alderman, Cheryl
AU - Scheer, Abigail
AU - Borner, Irmgard
AU - Bethea, Terrence C.
AU - Edwards, Sarah
AU - Hamer, Robert M.
AU - Riddle, Mark A.
N1 - Publisher Copyright:
© 2020 World Psychiatric Association
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - Antipsychotics
KW - IMPACT
KW - antipsychotic switch
KW - healthy lifestyle education
KW - metformin
KW - obesity
KW - weight gain
KW - youth
UR - http://www.scopus.com/inward/record.url?scp=85077534527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077534527&partnerID=8YFLogxK
U2 - 10.1002/wps.20714
DO - 10.1002/wps.20714
M3 - Article
C2 - 31922663
AN - SCOPUS:85077534527
SN - 1723-8617
VL - 19
SP - 69
EP - 80
JO - World Psychiatry
JF - World Psychiatry
IS - 1
ER -