Do antipsychotics increase diabetes risk in children and adolescents?

Abstract

Introduction: 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.

Areas covered: 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).

Expert opinion: 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.

Keywords:

• adolescents
• antipsychotics
• children
• diabetes
• glucose
• hemoglobin A1c
• healthy controls
• incidence
• insulin
• psychiatric controls

Declaration of interest

The work was partially supported by the National Institute of Mental Health Advanced Center for Services and Intervention Research, the Zucker Hillside Hospital (P30MH090590). CU Correll has been a consultant and/or advisor to or has received honoraria from Bristol-Myers Sqibb, Eli Lilly, Genetech, Gerson Lehman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Supernus and Takeda. He has received grant support from the American Academy of Child and Adolescent Psychiatry BMS, Janssen/J&J, National Institute of Mental Health, Novo Nirdisk A/S, Ostuka, Takeda and the Thrasher Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.