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

Abstract

Background: Iron deficiency disrupts dopaminergic signaling in rodents, resulting in cognitive deficits that may be reversed with psychostimulants. In humans, iron deficiency with or without anemia has similarly been found to cause neuropsychological and behavioral impairments. However, the clinical effects of low body iron stores in antipsychotic-treated children have not been examined. Methods: Medically healthy, 5-to 17-year-old boys treated with risperidone for at least 1 year were enrolled between February 2009 and November 2013 in a multiphase study, examining the skeletal effects of calcium and vitamin D supplementation in risperidone-induced hyperprolactinemia. Anthropometric measures were collected and medical and pharmacy records were reviewed to obtain treatment history. Psychiatric diagnoses were based on clinical interviews, structured interviews, rating scales, and a review of their medical records. Extrapyramidal symptoms were assessed, and a food frequency questionnaire was completed in a subsample. Laboratory tests, including ferritin concentration (a marker of body iron status), were obtained upon study entry. Results: A total of 114 participants (mean age: 11.0 -2.6 years) were included, the vast majority (>90%) having attentiondeficit/hyperactivity disorder and/or disruptive behavior disorder. They had taken risperidone for an average 3.1 -2.0 years. Their serum ferritin concentration was 37.3 -25.6 lg/L with 21% of the sample having a level <20 lg/L, despite appropriate daily dietary iron intake. Ferritin concentration was inversely associated with weight gain following risperidone treatment onset but was not significantly associated with prolactin. After adjusting for the weight-adjusted dose of psychostimulants and risperidone and the daily dose of selective serotonin reuptake inhibitors, ferritin was inversely associated with the severity of disruptive behavior and positively associated (albeit marginally) with prosocial behavior. No association was found between ferritin concentration and extrapyramidal symptoms. Conclusions: Body iron stores are inversely related to risperidone-induced weight gain, even after extended treatment and despite adequate iron intake. Low iron stores are associated with poorer treatment response. Future research should examine iron absorption during antipsychotic treatment and whether repleting iron stores would facilitate clinical response.

The Other Obesity Epidemic—Of Drugs and Bugs

“…In addition, impaired iron absorption may activate nutritional immunity in IECs and macrophages to sequestrate this biometal and deny it to pathogens, exacerbating hypoferremia and metabolic syndrome ( 133 , 134 ). On this point, a novel study in children and adolescents chronically treated with RSP found that iron status was inversely corelated with weight gain, contributing to dysmetabolic iron overload syndrome (DIOS) ( 135 ). This is significant as intracellular iron increases the risk of ROS generation that cannot be counteracted as Bacteroidetes depletion lowered IPA, a key gut antioxidant ( 98 , 136 , 137 ).…”

Integrative Management of Metabolic Syndrome in Youth Prescribed Second-Generation Antipsychotics

“…Another factor that may be implicated in SGA-induced weight gain is the body’s intracellular storage of iron, as measured by ferritin [ 35 , 36 , 37 ]. Low ferritin, indicating low bodily iron stores, is possible independent of anemia as measured by low hemoglobin and hematocrit [ 37 ]. This could be particularly relevant in youth whose bodies are growing and require sufficient intracellular iron stores [ 37 ].…”

“…Low ferritin, indicating low bodily iron stores, is possible independent of anemia as measured by low hemoglobin and hematocrit [ 37 ]. This could be particularly relevant in youth whose bodies are growing and require sufficient intracellular iron stores [ 37 ]. Combining vertical growth with weight gain can deplete bodily iron stores more rapidly [ 37 ].…”

Pharmacotherapy in Psychiatric Disorders of Children: Current Evidence and Trends

“…Both FGAs and SGAs can cause debilitating adverse drug reactions (ADR), which require the clinician weighing the need for treatment against the potential costs like ADRs as weight gain, metabolic syndrome, extrapyramidal symptoms (EPS), etc. [31,[36][37][38]. Among the SGAs, risperidone is the most extensively studied medication for the treatment of aggression and CD in children and adolescents.…”

“…A meta-analysis of the effect of risperidone in reducing symptoms of aggression including 875 subjects (mostly boys with a mean age of about 9 years) reported a large ES of 0.9 [33]. Other SGAs may be preferred if they cause less weight gain, which is the most relevant ADR of risperidone [38]. In the literature, there are indications that mood stabilizers can also reduce aggression associated with CD.…”