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Original Investigation |

Antipsychotics and the Risk of Type 2 Diabetes Mellitus in Children and Youth

William V. Bobo, MD, MPH1; William O. Cooper, MD, MPH2; C. Michael Stein, MB, ChB3; Mark Olfson, MD, MPH4; David Graham, MD, MPH5; James Daugherty, MS6; D. Catherine Fuchs, MD1; Wayne A. Ray, PhD6
[+] Author Affiliations
1Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee
2Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
3Division of Clinical Pharmacology, Department of Internal Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
4Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York
5US Food and Drug Administration, Silver Spring, Maryland
6Division of Pharmacoepidemiology, Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
JAMA Psychiatry. 2013;70(10):1067-1075. doi:10.1001/jamapsychiatry.2013.2053.
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Importance  The increased prescribing of antipsychotics for children and youth has heightened concerns that this practice increases the risk of type 2 diabetes mellitus.

Objective  To compare the risk of type 2 diabetes in children and youth 6 to 24 years of age for recent initiators of antipsychotic drugs vs propensity score–matched controls who had recently initiated another psychotropic medication.

Design, Setting, and Participants  Retrospective cohort study of the Tennessee Medicaid program with 28 858 recent initiators of antipsychotic drugs and 14 429 matched controls. The cohort excluded patients who previously received a diagnosis of diabetes, schizophrenia, or some other condition for which antipsychotics are the only generally recognized therapy.

Main Outcomes and Measures  Newly diagnosed diabetes during follow-up, as identified from diagnoses and diabetes medication prescriptions.

Results  Users of antipsychotics had a 3-fold increased risk for type 2 diabetes (HR = 3.03 [95% CI = 1.73-5.32]), which was apparent within the first year of follow-up (HR = 2.49 [95% CI = 1.27-4.88]). The risk increased with cumulative dose during follow-up, with HRs of 2.13 (95% CI = 1.06-4.27), 3.42 (95% CI = 1.88-6.24), and 5.43 (95% CI = 2.34-12.61) for respective cumulative doses (gram equivalents of chlorpromazine) of more than 5 g, 5 to 99 g, and 100 g or more (P < .04). The risk remained elevated for up to 1 year following discontinuation of antipsychotic use (HR = 2.57 [95% CI = 1.34-4.91]). When the cohort was restricted to children 6 to 17 years of age, antipsychotic users had more than a 3-fold increased risk of type 2 diabetes (HR = 3.14 [95% CI = 1.50-6.56]), and the risk increased significantly with increasing cumulative dose (P < .03). The risk was increased for use restricted to atypical antipsychotics (HR = 2.89 [95% CI = 1.64-5.10]) or to risperidone (HR = 2.20 [95% CI = 1.14-4.26]).

Conclusions and Relevance  Children and youth prescribed antipsychotics had an increased risk of type 2 diabetes that increased with cumulative dose.

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Figure 1.
Cumulative Incidence of Type 2 Diabetes Mellitus, According to Baseline Antipsychotic Use and Using the Kaplan-Meier Method

HR, hazard ratio (adjusted).

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Figure 2.
Adjusted Annual Incidence of Type 2 Diabetes Mellitus Among Children and Youth 6 to 17 Years of Age, According to Cumulative Antipsychotic Dose

The vertical bars represent 95% CIs. The P value is for the test for the dose-response relationship. Adjusted incidence was calculated by multiplying the incidence in the control group by the hazard ratio, with an analogous calculation for the 95% CIs.

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Figure 3.
Risk of Type 2 Diabetes Mellitus for Antipsychotic Users Within Subgroups Defined by Baseline Cohort Characteristics

No., number of cases of type 2 diabetes; P-y, person-years of follow-up.

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