Do antipsychotics increase diabetes risk in children and adolescents?

Glucose dysregulation and type 2 diabetes mellitus (T2DM) are feared antipsychotic drug adverse effects. Despite increasing utilization, data about antipsychotic risk of T2DM in youth are scarce.

We conducted a systematic PubMed/MEDLINE search until 15 May 2014 focusing on studies with ≥ 20 youths aged ≤ 24 years, reporting quantitative data on: i) change in fasting glucose, hemoglobin A1c, insulin or insulin resistance after antipsychotic initiation (studies = 19, n = 2123,age = 13.3 years, follow up = 28.8 weeks); or ii) prevalence (studies = 4) or incidence (studies = 8, follow up = 1.57 years) of T2DM in antipsychotic-exposed youth (studies = 10, n = 65,486, age = 14.2 years) versus healthy controls (studies = 4, n = 246,828), psychiatric controls (studies = 5, n = 61,784) or without control groups (studies = 2).

Antipsychotics are associated with early adverse changes in glucose metabolism that are greater with all analyzable antipsychotics compared to controls, being highest with olanzapine, followed by quetiapine, aripiprazole and risperidone; but data were scarce. Although T2DM is fortunately rare in antipsychotic-treated youth, its prevalence (odds ratio [OR] = 8.176, 95% CI = 7.139 - 9.362) and incidence (OR = 1.450, 95% CI = 1.101 - 1.911, p = 0.006) were higher than in healthy controls. Similarly, T2DM prevalence (OR = 3.475, 95% CI = 3.019 - 4.001, p < 0.0001) and incidence (OR = 5.376, 95% CI = 4.004 - 7.233, p < 0.0001, excluding one outlying study) were higher than in psychiatric controls. Antipsychotics should only be used after lower-risk interventions failed, and inappropriately low clinical metabolic monitoring must be remedied.