Antipsychotic medications appear to triple the risk of type 2 diabetes in children and teens, with most of the risk occurring in the first year of administration.
A retrospective study of more than 43,000 youths found the same threefold increase, no matter how the data were analyzed, Dr. William V. Bobo and his colleagues reported in the Aug. 21 online edition of JAMA Psychiatry (JAMA Psych 2013 [doi:10.1001/jamapsychiatry.2013.2053]).
The risk translated into an additional 15.8 cases of type 2 diabetes per person-year of antipsychotic treatment, with a number needed to harm of 633, wrote Dr. Bobo of Vanderbilt University in Nashville, Tenn., and his associates.
The investigational cohort consisted largely of Medicaid enrollees, "which limits the generalizability of study findings, given that the incidence of type 2 diabetes in children covered by Medicaid may be elevated owing to economic and social factors, as well as to a greater prevalence of behavioral risk factors, disability, and chronic illness."
The study population included 43,287 children and young people aged 6-24 years, all of whom were enrolled in the Tennessee Medicaid system. Of these, 28,858 had recently initiated antipsychotic therapy. The remainder served as matched controls and had recently started taking other psychotropic – but not antipsychotic – medications.
No matter how the data were cut, the increased risk for type 2 diabetes hovered right around threefold. For children aged 6-17 years, antipsychotics conferred an increased risk of 3.14.
The cohort was a mean of 14 years old; 26% of those in each group were disabled enrollees. The most common diagnoses were mood disorders (including bipolar disorder), attention-deficit/hyperactivity disorder, and conduct disorder. About a quarter had undergone some form of glucose testing within the prior year, although the authors said that metabolic disorders were "relatively infrequent."
Most of the antipsychotic users (87%) were taking an atypical, the most commonly prescribed of which was risperidone (37% of that group). Quetiapine and olanzapine were the next most commonly used (20% each). The median starting dose for antipsychotic users was 67 mg of chlorpromazine equivalents.
There were nearly 56,000 person-years of follow-up in the study. During that time, 21 incident cases of type 1 diabetes developed – a rate of 3.8 per 10,000 person-years. Those cases consisted of patients who were a mean of 13 years old. Most (62%) were male. The rate of type 1 diabetes was not significantly different between those taking antipsychotics and those not taking them (hazard ratio, 1.13).
There were 106 incident cases of type 2 diabetes – a rate of 19 cases per 10,000 person-years. The mean age of these cases was 16.7 years; 37% were male. Young people who took antipsychotic medications were three times more likely to develop type 2 diabetes than those who did not take the drugs (HR, 3.03). The increased risk appeared within the first year of follow-up (HR, 2.49) and increased in a dose-dependent fashion. The risk for those taking a cumulative dose of 100 g or more of chlorpromazine equivalents was 5.43; however, the risk associated with a cumulative dose of less than 5 g was 2.13. The risk remained significantly increased for up to a year after antipsychotics were discontinued (HR, 2.57).
No matter how the data were cut, the increased risk for type 2 diabetes hovered right around threefold. For children aged 6-17 years, antipsychotics conferred an increased risk of 3.14. The risk was similar when subgroups were defined by age, gender, presence of bipolar disorder, psychostimulant use, or a diagnosis of either ADHD or conduct disorder.
Several sensitivity analyses came to the same conclusion, including several that controlled for clustering induced by the frequency matching (HR, 3.07), restricted the cohort to new users of antipsychotics and control medications (HR, 3.05), did not permit antipsychotic users who left the cohort to reenter (HR, 2.86), and used a prescription for an antidiabetic medication as the definition of diabetes (HR, 3.11).
The authors noted that this type of sudden-onset diabetes appears contradictory to the chronic pathophysiology normally associated with the disease development. "Cases of early-onset antipsychotic-associated diabetes have been reported for adults," they said. "In one series, the majority of cases occurred within 6 months of drug initiation. ... Further study of the pathophysiology of antipsychotic-associated diabetes is needed."
Dr. Bobo has received research support from Cephalon and served on speaker bureaus for Janssen Pharmaceuticals and Pfizer. The study was supported by the Agency for Healthcare Research and Quality/Centers for Education and Research on Therapeutics cooperative agreement.
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