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Side effects of widely prescribed antipsychotic drugs the focus of $1.2M NIH grant awarded to UNE researcher Karen Houseknecht

Karen Houseknecht

June 28, 2013

The U.S. National Institutes of Health (NIH) reports that as diagnoses of mental health disorders have risen among children over the past two decades, more children have been prescribed antipsychotic medications, often "off label."

Second-generation antipsychotics (SGAs) are widely prescribed to adults and children for the treatment of schizophrenia, bipolar disorder, attention deficit disorder and other conditions.

These drugs are also increasingly being prescribed off-label to treat a number of other ailments, including attention-deficit/hyperactivity disorder (ADHD), especially among poor children1 , both nationally and in Maine2 , as an alternative to stimulants such as Ritalin, which are FDA-approved for the treatment of ADHD.

Karen L. Houseknecht, Ph.D., professor of pharmacology at the University of New England (UNE) Department of Pharmaceutical Sciences, studies the potentially serious and lasting side effects of SGAs, such as type 2 diabetes, obesity, and bone loss.  

She has just received a four-year, $1.2 million grant from the National Institutes of Health to further study the effects of SGA medications on bone biology, and to identify the underlying mechanisms by which these drugs cause bone loss, with the ultimate goals of informing the discovery and development of safer antipsychotic medications and identifying co-therapies that will minimize side effects in patients currently taking SGA medications.

Houseknecht's research focuses on the underlying pharmacological mechanisms of SGA drugs, including the mostly widely prescribed drug, risperidone. In her previous work, Houseknecht has published that SGA drugs such as olanzapine and clozapine can induce severe insulin resistance following a single clinically relevant dose, consistent with the clinical findings that SGA drugs cause significant weight gain and diabetes in many patients. 

More recently, clinical reports indicate increased risk of fractures in patients taking SGA drugs, including risperidone. Last year Houseknecht and her collaborators at Maine Medical Research Institute published work showing that risperidone treatment of adolescent mice results in significant bone loss, indicating significant risk for adolescent patients being administered this medication.

She states, "Though effective for the treatment of serious mental illness such as schizophrenia and bipolar disorder, SGAs are very powerful drugs with serious side effects that can have lasting health consequences for millions of adults and children. Our research may better inform physicians and parents about the possible side effects related to these drugs, and perhaps lead to identification of co-therapies to counteract these deleterious effects."

Houseknecht's research, "Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain," is published in the journal Bone and co-authored with Maine researchers Clifford Rosen, M.D., and Katherine Motyl, Ph.D., from the Maine Medical Center Research Institute. Rosen is director of the Center for Clinical and Translational Research at Maine Medical Center, and an expert on bone osteoporosis.

1Health Serv Res. 2012 Oct;47(5):1836-60. doi: 10.1111/j.1475-6773.2012.01461.x. Epub 2012 Sep 4:The relationship between mental health diagnosis and treatment with second-generation antipsychotics over time: a national study of U.S. Medicaid-enrolled children.:Matone M, Localio R, Huang YS, dosReis S, Feudtner C, Rubin D.

2Antipsychotic Medication Use in medicaid Children and Adolescents: Report and resource guide from a 16-state study. MMDLN/Rutgers CERTs Publication #1. July 2010. Distributed by Rugers CERTs


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