According to the results of a retrospective cohort study, the use of second-generation antipsychotics (SGAs) for the treatment of bipolar disorder, autism and other mental disorders in children may be associated with an increased risk of diabetes.

The authors note that use of SGAs among children and adolescents has increased substantially, despite lack of data on safety and efficacy for most indications (the majority of use is off-label).  Previous research has suggested a link between use of antipsychotics and diabetes mellitus, impaired glucose tolerance and insulin resistance in adults (although the evidence is inconsistent); data for children are more limited.  The objective of the current study was to evaluate the risk of incident diabetes associated with the use of SGAs in a large diverse cohort of children treated in typical clinical practice.

Researchers retrospectively analysed data from three US health plans, identifying children aged 5-18 years who initiated SGA treatment between Jan 2001 and Dec 2008, and comparing them to two other groups: a) non-users of psychotropic drugs during the observation period; and b) new users of antidepressants (selective serotonin reuptake inhibitors or tricyclic antidepressants).  The databases were used to identify potential cases of diagnosed and/or treated diabetes (either via inpatient or outpatient diagnosis code; dispensing of an anti-diabetic medication; or laboratory test results). 

A total of 9,636 children started on a SGA during the study period; these were compared to 38,544 using no psychotropic and 26,265 who were started on an antidepressant.  Of the entire study group, 57 children were diagnosed with diabetes during the study period.  The main findings were as follows:

• The crude incidence rate of diabetes for those treated with SGAs was 3.23 cases per 1000 person-years (95% CI 1.67–5.65), compared to 0.76 cases per 1000 person-years (95% CI 0.49–1.12) among non-users of psychotropic medications (unadjusted incidence rate ratio: 4.24 [95% CI 1.95–8.72])

• The crude incidence rate of diabetes for those who started treatment with antidepressants was 1.86 cases per 1000 person-years (95% CI: 1.12–2.90) – this was numerically lower than those treated with SGAs but not statistically significantly so (unadjusted incidence rate ratio: 1.74 [95% CI 0.77–3.78]).

The authors acknowledge the limitations of their study, including the low number of new diabetes cases, the possibility of cases of undiagnosed diabetes, and the possibility of residual confounding, as they did not evaluate potential confounders such as baseline BMI, diet, exercise race/ethnicity, severity of underlying mental health conditions, and long-term use.

They conclude that there was a potentially four-fold increase in the risk of diabetes in children taking SGAs compared to those not taking any psychotropic medications; however the findings were inconsistent and depended on the comparison group and the outcome definition.  Additional research is required to confirm these findings, and the nature and magnitude of any diabetes risk associated with SGA use among children.