03. Cardiac and Metabolic Safety Profile of Antipsychotics in Youth

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Hi! David Rosenberg is here for the Psychopharmacology Institute. In this CAP—or Child and Adolescent Psychiatry—Smart Take, we will closely examine the cardiac and metabolic safety profile of antipsychotics in youth via a World Health Organization Safety Database analysis. This is especially timely as youth treated with antipsychotics are believed to be more vulnerable and at higher risk of developing cardiometabolic side effects compared with their adult counterparts. The focus of this study was to identify age-dependent reporting of cardiac and metabolic disorders in youth treated with antipsychotics using the World Health Organization database.

Specifically, they looked at all reports of cardiac, glucose, lipid, and nutritional disorders associated with antipsychotic treatment in patients less than 18 years of age. All told, this approach yielded over 4,600 pediatric reports. Nutritional disorders were found to be highest in youth, with significantly stronger signals detected in youth than adults when relying on healthcare professional reports. These signals were significantly stronger in children compared with both adolescents and adults.

In adolescents, aripiprazole was associated with nonalcoholic steatohepatitis. The real advantage of this study is that the findings are based on real-world data and showed a greater risk for nutritional disorders in youth. The authors recommended specific safety profiles, particularly for aripiprazole and nonalcoholic steatohepatitis in adolescents, with cautious monitoring warranted in all youth treated with antipsychotic medications. This is very important given how the rate of prescription of antipsychotics, particularly second-generation antipsychotics, which have the highest risk for metabolic abnormalities, has so dramatically increased in youth. The high prevalence of cardiac and nutritional disorders in young people, particularly in the youngest population, is of great concern. In this analysis, the association between risperidone and obesity was also especially noteworthy, as was the aripiprazole in nonalcoholic steatohepatitis.

The above being said, it is very important to note that no causal association can be drawn from this study or any of the aforementioned findings. The study was not designed to identify causality. There is a huge difference between a possible association and cause and effect. Moreover, a reasonableness perspective is needed. The majority of children and adolescents can be treated safely and effectively with antipsychotics when they are used at the appropriate dose and duration and for the proper diagnosis. When prescribed correctly, these medicines do enormous good. However, they are not without side effects, which can be significant and require close monitoring, vigilance, and being proactive and prepared to intervene promptly—that is, having an action plan in the event of side effects and properly informing the patients, their parents, and caregivers before starting the medicine.

So, what is the bottom line? This is an important study in a very understudied area and underscores the vigilance, caution, and close monitoring we need to exercise when prescribing antipsychotics to youth. This does not mean we should not prescribe these medicines. Still, it does mean they must be closely monitored in youth who may be especially susceptible to possible cardiac, metabolic, and nutritional effects.

Some people will be concerned that antipsychotics are dangerous to prescribe in youth and that the risk–benefit ratio is not in their favor. From my clinical experience, I must reiterate that the conditions that antipsychotics are prescribed for are highly debilitating, chronic, and severe. These illnesses cause significant impairment to patients’ quality of life. In my opinion, when these medications are prescribed appropriately for the correct diagnosis, they can be more beneficial than harmful. However, we always need to keep an eye out for possible side effects that may arise.

Abstract

Cardiac and Metabolic Safety Profile of Antipsychotics in Youths: A WHO Safety Database Analysis

Diane Merino, Alexandre O Gérard, Alexandre Destere, Haitam Saidessalam, Florence Askenazy, François Montastruc, Milou-Daniel Drici, Susanne Thümmler

A significant heterogeneity prevails in antipsychotics (APs) safety monitoring recommendations. Youths are deemed more vulnerable to cardiometabolic side effects. We aimed to assess age-dependent reporting of cardiac and metabolic disorders in youths, relying on the WHO safety database (VigiBase®). VigiBase® was queried for all reports of cardiac, glucose, lipid and nutritional disorders involving APs. Patients <18 years were classified as pediatric population. Disproportionality analyses relied on the Information Component (IC): the positivity of the lower end of its 95 % confidence interval was required to suspect a signal. We yielded 4,672 pediatric reports. In disproportionality analysis, nutritional disorders were leading in youths (IC 3.9 [3.9-4.0]). Among healthcare professionals' reports, stronger signals were detected in youths than in adults. Children had the greatest signal with nutritional disorders (IC 4.7 [4.6-4.8]). In adolescents, aripiprazole was ascribed to non-alcoholic steatohepatitis (NASH). Our findings, based on real-world data, support the hypothesis of a greater propensity for nutritional disorders in youths, despite limitations of pharmacovigilance studies. We suggest specific safety profiles, such as aripiprazole and NASH. Pending more answers from population-based studies, a careful anamnesis should seek for risk factors before AP initiation. A cautious monitoring is warranted to allow earlier identification of side effects.

Reference

Merino, D., Gérard, A. O., Destere, A., Saidessalam, H., Askenazy, F., Montastruc, F., Drici, M., & Thümmler, S. (2024).

Cardiac and metabolic safety profile of antipsychotics in youths: A WHO safety database analysis.

Psychiatry Research, 334

, 115786