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Iron homeostasis during risperidone treatment in children and adolescents
Chadi A Calarge1, Ekhard E Ziegler, Nicole Del Castillo
1Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Ave, Suite 790, Houston, TX 77030 chadi.calarge@bcm.edu.
Insights
Risperidone use in children with autism spectrum disorder is linked to weight gain and lower iron levels. Weight loss after stopping risperidone may improve iron reserves, suggesting a direct effect on iron absorption.
Area of Science:
- Pediatric Psychiatry
- Neurodevelopmental Disorders
- Nutritional Science
Background:
- Antipsychotic medications, such as risperidone, are used to manage disruptive behaviors in children with autism spectrum disorder.
- Previous studies suggest a link between antipsychotic-induced weight gain and reduced body iron concentration.
- Longitudinal data are needed to clarify the relationship between weight changes and iron status during risperidone treatment.
Purpose of the Study:
- To investigate the longitudinal association between changes in weight and ferritin concentration following risperidone initiation or discontinuation in children.
- To explore whether risperidone directly impacts iron absorption or reserves.
Main Methods:
- Two studies were conducted: a prospective randomized trial (Study 1) and an observational follow-up study (Study 2) in children with autism spectrum disorder.
- Study 1 involved children initiating risperidone, while Study 2 included children on long-term risperidone treatment.
- Ferritin concentration and body mass index (BMI) z-score changes were measured, and linear regression analysis was used to assess associations.
Main Results:
- In Study 1, risperidone initiation was associated with increased BMI z-scores and decreased ferritin concentration, with a significant inverse correlation between BMI change and ferritin change.
- In Study 2, while overall changes in BMI and ferritin did not differ between risperidone continuers and discontinuers, weight loss after discontinuation was linked to higher ferritin levels.
- These findings suggest that weight gain during risperidone treatment is associated with reduced iron reserves.
Conclusions:
- Risperidone-associated weight gain is linked to a decrease in body iron reserves.
- Weight loss following risperidone discontinuation appears to improve iron status.
- Preliminary evidence suggests risperidone might directly inhibit iron absorption.
Objective:
Previous cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration.
Method:
Study 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders.
Results:
Study 1 sample consisted of 73 participants (85% males, mean age: 7.7 ± 2.4 years). After 18.0 ± 2.0 weeks on risperidone, their BMI z score increased by 0.93 ± 0.70 points and ferritin concentration declined by 6.8 ± 13.3 μg/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (β = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 ± 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01).
Conclusions:
Risperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption.
Trial Registration:
ClinicalTrials.gov Identifier: NCT00080145.
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