ABSTRACT
Objective: This study aimed to assess the effectiveness of metformin for antipsychotic-induced weight gain (AIWG) and determine whether the timing of metformin initiation and premorbid obesity moderated metformin effectiveness in children and adolescents on treatment with second-generation antipsychotics (SGAs).
Methods: A cohort of individuals 6 to 17 years of age, from 2016 to 2021, initiating a new SGA treatment and receiving a subsequent metformin prescription during SGA treatment were identified from the IQVIA Ambulatory EMR-US database. The changes in body mass index (BMI) z score before and after metformin initiation were assessed using the piecewise linear mixed-effects regression model.
Results: The results showed that the initiation of metformin was associated with a flattening out of the prior-metformin BMI z score trend. Relative to those who did not use metformin, metformin users had an additional monthly decrease in BMI z score of –0.053 (P = .0008) during the 6-month period after metformin initiation. Specifically, users who were non-obese before the intervention experienced a greater reduction in the BMI z score slope compared to those who were mildly-to-moderately obese and severely obese (non-obese – mildly-to-moderately obese: −0.07631, P = .0001; non-obese – severely obese: −0.09613, P < .0001). A different effect was not observed between patients who initiated metformin within versus beyond 90 days of SGA initiation. Extending the observation period to 12 months yielded comparable findings.
Conclusions: Adjuvant metformin helps manage AIWG in children and adolescents by flattening the upward AIWG trend rather than reversing it. The effect was more prominent before the development of obesity, suggesting that the early introduction of metformin for AIWG management may be warranted.
J Clin Psychiatry 2024;85(1):23m14894
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References (21)
- Dayabandara M, Hanwella R, Ratnatunga S, et al. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat. 2017;13:2231–2241. PubMed CrossRef
- Lee A, Morley JE. Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res. 1998;6(1):47–53. PubMed CrossRef
- Klein DJ, Cottingham EM, Sorter M, et al. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry. 2006;163(12):2072–2079. PubMed CrossRef
- Arman S, Sadramely MR, Nadi M, et al. A randomized, double-blind, placebo-controlled trial of metformin treatment for weight gain associated with initiation of risperidone in children and adolescents. Saudi Med J. 2008;29(8):1130–1134. PubMed
- Anagnostou E, Aman MG, Handen BL, et al. Metformin for treatment of overweight induced by atypical antipsychotic medication in young people with autism spectrum disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73(9):928–937. PubMed CrossRef
- Correll CU, Sikich L, Reeves G, et al. Metformin 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. World Psychiatry. 2020;19(1):69–80. PubMed CrossRef
- de Silva VA, Suraweera C, Ratnatunga SS, et al. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16(1):341. PubMed CrossRef
- Doyle DL, Sood R. IQVIA. A Diagnostic Framework to Evaluate Real-World Data Sources for Real-World Evidence Generation. 2018. https://www.iqvia.com/-/media/iqvia/pdfs/isporbarcelona2018posters/november-12/a-diagnostic-framework-to-evaluate-real-world-data-sources-for-real-world-evidence-generation.pdf. Accessed July 5, 2023.
- Zhou Z, Rahme E, Abrahamowicz M, et al. Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol. 2005;162(10):1016–1023. PubMed CrossRef
- Desai RJ, Mahesri M, Abdia Y, et al. Association of osteoporosis medication use after hip fracture with prevention of subsequent nonvertebral fractures: an instrumental variable analysis. JAMA Netw Open. 2018;1(3):e180826. PubMed CrossRef
- About Child & Teen BMI | Healthy Weight, Nutrition, and Physical Activity | CDC. CDC. Accessed July 31, 2022. https://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html
- Growth Charts - Clinical Growth Charts. CDC. Accessed July 31, 2022. https://www.cdc.gov/growthcharts/clinical_charts.htm
- Mizuno Y, Suzuki T, Nakagawa A, et al. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2014;40(6):1385–1403. PubMed CrossRef
- Patel A, Chan W, Aparasu RR, et al. Effect of psychopharmacotherapy on body mass index among children and adolescents with bipolar disorders. J Child Adolesc Psychopharmacol. 2017;27(4):349–358. PubMed CrossRef
- Rummel-Kluge C, Komossa K, Schwarz S, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010;123(2-3):225–233. PubMed CrossRef
- Cleveland WS. LOWESS: A program for smoothing scatterplots by robust locally weighted regression. Am Stat. 1981;35(1):54. CrossRef
- NIST. LOESS (aka LOWESS). NIST/SEMATECH e-Handbook of Statistical Methods. Accessed July 31, 2022. https://www.itl.nist.gov/div898/handbook/pmd/section1/pmd144.htm
- Naumova EN, Must A, Laird NM. Tutorial in Biostatistics: Evaluating the impact of ‘critical periods’ in longitudinal studies of growth using piecewise mixed effects models. Int J Epidemiol. 2001;30(6):1332–1341. PubMed CrossRef
- Fitzmaurice GM, Laird NM, Ware JH. Applied Longitudinal Analysis. 2012. Accessed July 5, 2023. https://books.google.com/books?hl=en&lr=&id=0exUN1yFBHEC&oi=fnd&pg=PR17&ots=BeqVV_sK1I&sig=MuhoJklAsRxv0BOPg4ufPREUrA8
- Calarge CA, Nicol G, Xie D, et al. Correlates of weight gain during long-term risperidone treatment in children and adolescents. Child Adolesc Psychiatry Ment Health. 2012;6(1):21. PubMed CrossRef
- Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302(16):1765–1773. PubMed CrossRef
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