Iron Deficiency in Pediatric Patients in Long-Term Risperidone Treatment

Abstract

Objective: Atypical antipsychotics, increasingly used in children and adolescents, modulate brain dopamine. Iron plays a critical role in dopaminergic signaling. Therefore, we explored whether body iron status is related to psychiatric symptom severity, treatment response, and tolerability following extended antipsychotic therapy. Methods: Between November 2005 and August 2009, medically healthy 7-17-year-old risperidone-treated participants enrolled in a cross-sectional study examining the long-term safety of this antipsychotic. Anthropometric measurements were obtained. Psychiatric symptom severity and dietary intake were assessed. Serum ferritin, transferrin receptor, and prolactin concentrations were measured. Linear multivariable regression analysis tested the association among body iron, symptom severity, the dose of risperidone and psychostimulants, and serum prolactin concentration. Results: The sample consisted of 115 patients (87% males) with a mean (-SD) age of 11.6 (-2.8) years. The majority had externalizing disorders, and they had taken risperidone for 2.4 (-1.7) years. Body iron was low, with 45% having iron depletion and 14% having iron deficiency. Iron status was inversely associated with weight gain during risperidone treatment and with interleukin-6. Body iron was neither associated with psychiatric symptom severity nor with the daily dose of risperidone and psychostimulants. It was, however, inversely associated with prolactin concentration, which was nearly 50% higher in the iron-deficient group. Conclusions: Iron depletion and deficiency are prevalent in children and adolescents chronically treated with risperidone. Iron deficiency accentuates the antipsychotic-induced elevation in prolactin. Future studies should confirm this finding and investigate the potential benefit of iron supplementation in antipsychotic-treated patients.

Serum Ferritin, Weight Gain, Disruptive Behavior, and Extrapyramidal Symptoms in Risperidone-Treated Youth

“…Finally, in contrast to our earlier finding (Calarge and Ziegler 2013), after adjusting for age ( p > 0.80), weight Z-score ( p > 0.10), the weight-adjusted dose of psychostimulants ( p > 0.80), SSRI dose ( p > 0.60), and the combined risperidone and 9-hydroxyrisperidone concentration ( p < 0.0001), ferritin concentration (natural log transformed) was not significantly associated with prolactin concentration ( p > 0.30).…”

“…Previously, we found risperidone-induced weight gain to be inversely associated with ferritin concentration following acute and chronic treatment (Calarge and Ziegler 2013;Calarge et al 2015b). In this study, we replicate this finding in a new group of participants and extend it by reporting an inverse association between ferritin concentration and externalizing symptom severity.…”

“…Depletion of body iron stores in association with risperidone-induced weight gain was also found in a longer term study, where we also reported that weight loss following the discontinuation of risperidone was associated with an improvement in serum ferritin (Calarge and Ziegler 2013;Calarge et al 2015b). Finally, preliminary evidence suggested that risperidone treatment might inhibit iron repletion because ferritin concentration remained low despite normal dietary iron intake and because ferritin concentration failed to increase in those who lost weight but continued on risperidone (Calarge and Ziegler 2013;Calarge et al 2015b). Of interest, the typical antipsychotic chlorpromazine has the potential to chelate iron and chronic chlorpromazine or haloperidol treatment has been associated with reduced hepatic nonheme iron in rats (Rajan et al 1974;Weiner et al 1977;Ben-Shachar and Youdim 1990;Ben-Shachar et al 1991).…”

“…In prior work, we have found that up to 59% of children and adolescents chronically treated with risperidone exhibited iron depletion/deficiency (Calarge and Ziegler 2013). Findings reported here reveal that the ALPCO kit we had used before suffers from low sensitivity, thus underestimating serum ferritin concentration.…”

“…The latter was available on 72% of the participants as we added it only after finding an elevated rate of low ferritin concentration in risperidone-treated children (Calarge and Ziegler 2013). In prior work (Calarge et al 2010(Calarge et al , 2015bCalarge and Ziegler 2013), we had measured ferritin through the core laboratory at the University of Iowa Hospitals and Clinics, using an Enzyme-linked Immunosorbent Assay Kit manufactured by ALPCO Diagnostics (Salem, NH). However, for the present study, a coauthor (E.E.Z.)…”