A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics

Benjamin U Nwosu, Bruce Meltzer, Louise Maranda, Carol Ciccarelli, Daniel Reynolds, Laura Curtis, Jean King, Jean A Frazier, Mary M Lee, Benjamin U Nwosu, Bruce Meltzer, Louise Maranda, Carol Ciccarelli, Daniel Reynolds, Laura Curtis, Jean King, Jean A Frazier, Mary M Lee

Abstract

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs.

Figures

Figure 1
Figure 1
(A) Comparison of changes in BMI percentiles in children who received molindone as compared with those who received olanzapine and risperidone. (B) Comparison of adverse metabolic effect of antipsychotic treatment experienced in subjects with early-onset schizophrenia and schizoaffective disorder (12). Reprinted with permission form the American Journal of Psychiatry (Copyright © 2008). American Psychiatric Association.
Figure 2
Figure 2
In vitamin D-deficient states, PTH accelerates the conversion of 25-OHD to 1,25(OH)2D3, which results in a compensatory increase in serum 1,25-dihydroxyvitamin D level, which drives the infl ux of calcium ions into the cell and consequent activation of FAS. Adapted from Zemel (81).

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