Metabolic Side Effects and Pharmacogenetics of Second-Generation Antipsychotics in Children

Abstract

Second-generation antipsychotics (SGAs) are increasingly being used to treat children for a range of mental health conditions, for example, anxiety disorder, attention deficit hyperactivity disorder and bipolar disorder. SGA treatment is associated with weight gain and cardiometabolic side effects such as dyslipidemia, insulin resistance and elevated blood pressure, in some, but not all children. This review provides an overview of the potential role of pharmacogenomics in predisposing a child to unhealthy weight gain and cardiometabolic side effects with SGA treatment. Specifically, the review includes a synopsis of the evidence for cardiometabolic side effects in SGA-treated children, illustrating the extent and depth of the problem; summarizes the potential long-term consequences of developing cardiometabolic risk during childhood and highlights genetic variants that may be useful in predicting cardiometabolic side effects in SGA-treated children.

The effects of antipsychotic medications on microbiome and weight gain in children and adolescents

“…While some countries have approved SGAs only for certain clinical indications, off-label use is also quite common [8]. These medications are sometimes prescribed for children as young as 2 years of age [9]. However, importantly, approximately 20% of patients who are prescribed SGAs are resistant to treatment, and in many cases, SGAs have unwanted side effects, such as weight gain [10].…”

“…Several studies indicate that hereditary factors may be involved in SGA-induced weight gain [9]. The level of olanzapine-induced weight gain in mice was found to be strain-dependent when tested in eight different mouse strains: one strain (C57BL/6 J) was found to be specifically susceptible to olanzapine-induced weight gain [49].…”

AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis

“…SGAs have been increasingly prescribed for offlabel conditions such as anxiety, attention deficit hyperactivity disorder (ADHD), insomnia and chemotherapy-induced nausea (Maher et al, 2011;Pringsheim and Gardner, 2014;Devlin and Panagiotopoulos, 2015;Bun et al, 2017;Chelkeba et al, 2017). SGAs, such as olanzapine (OLZ), have numerous metabolic side effects (Newcomer, 2005).…”

Executive Function Deficits in Seriously Ill Children—Emerging Challenges and Possibilities for Clinical Care

“…This can lead to side effects concerning other cognitive functions and may interfere with pharmacological strategies addressing the somatic manifestations of the underlying disease. For example, pharmacological interventions targeting executive function deficits can induce cardio-metabolic changes and lowered arousal in the case of neuroleptics ( 49 ), and can lead to sleep problems, weight loss, and mood changes in the case of MPH ( 50 ). Therefore, medication may not always represent a practicable solution in clinical practice, also because it can, at least currently, hardly be tailored to the individual patients (see Table 1 ).…”