Current strategies for predicting side effects from second generation antipsychotics in youth

ABSTRACT

Introduction: Antipsychotic medications are used to treat a number of conditions in children and adolescents. While side effect profiles from second generation antipsychotics (SGAs) may differ from older antipsychotics, they do not come without risk. Knowing which children may be at higher risk for specific outcomes is important clinical information for prescribers. Common side effects and toxicities of SGAs in children include movement disorders, weight gain, and hormonal changes. There are also rare, but potentially dangerous adverse events including neuroleptic malignant syndrome, hypersensitivity and suicidal ideation.

Areas covered: This review will summarize and comment on clinical, pharmacological, and genetic factors having evidence as predictors of SGA-associated side effects and toxicities in children.

Expert opinion: Observations across studies note that older children and those that do not respond early in treatment may be more at risk for movement disorders, while younger, antipsychotic naive children are at increased risk for weight gain. Relatively fewer studies have looked at pharmacogenetic relationships, although variations in pharmacokinetic and pharmacodynamic genes hold promise to advance drug dosing or selection strategies. Future efforts to assimilate multiple clinical, pharmacological, and genetic factors to facilitate predictive analytics and clinical decision support for prescribers will advance precision care to patients.

KEYWORDS:

• Antipsychotics
• children
• pediatrics
• adverse events
• side effects
• toxicity
• movement disorders
• weight gain
• prolactin
• pharmacogenetics

Declaration of interest

J Bishop has served as a consultant for OptumRx. 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.

Article highlights

• Prescribing of second-generation antipsychotics for youth increased after their intitial approvals for adults. Recent studies, however, suggest prescribing of these agents may now be decreasing in certain pediatric populations.

• Studies assessing associations of clinical characteristics with specific adverse events are more common than studies assessing predictive value.

• The most commonly reported side effects from second-generation antipsychotics in children are movement disorders, weight gain, and metabolic/hormonal changes.

• The most commonly reported associations between clinical characteristics of side effects were age, exposure, and specific genetic variants.

• Future studies designed to assess the predictive value of certain clinical characteristics would be useful knowledge for patients, parents, and prescribers.

This box summarizes key points contained in the article.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.