Safety and Tolerability of Antipsychotic Drugs in Pediatric Patients: Data From a 1-Year Naturalistic Study

Abstract

Background: Antipsychotic drugs (APs) are increasingly used to treat a variety of psychiatric disorders in children and adolescents. However, their safety and tolerability profiles, when used in a developmental age context, show different characteristics from the ones observed in adult patients. Treatment with APs in pediatric patients is often long-term. However, the tolerability data regarding these patients mostly derive from short-term studies.Methods: Starting from April 2017, for a 1-year period, patients between 4 and 18 years of age followed by five units of developmental age neuropsychiatry, who initiated a treatment with at least an AP (ATC class N05A) were included into the study. Patient-related data have been collected at baseline and regularly thereafter, as allowed by the clinical routine. Changes to continuous variables over time have been analyzed using a linear mixed model in subsamples of our population treated with risperidone or aripiprazole.Results: During the observation period, 158 patients were initially enrolled, but only 116 completed 12 months of therapy with an AP. Risperidone was the most used AP (n = 52) followed by aripiprazole (n = 44) and olanzapine (n = 7). For both the aripiprazole and risperidone groups, the mean body mass index (BMI) (P < 0.001 for both groups) and heart rate (P = 0.026 for aripiprazole group and P < 0.001 for the risperidone one) values significantly increased over time. The mean prolactin concentration value significantly increased over time only in the risperidone group (P = 0.04). Eighty-six patients experienced at least one adverse drug reaction (ADR), accounting for a total of 238 specific reactions, with the most frequent being weight gain (n = 34), increased serum prolactin levels (n = 21), hyperphagia (n = 20), and hypercholesterolemia (n = 14). Among these, only 24 ADRs were classifiable as serious.Cicala et al. Antipsychotic Drugs in Pediatric PatientsConclusions: The results of this study confirm that risperidone and aripiprazole are relatively well-tolerated therapeutic options for the treatment of a variety of psychiatric disorders in pediatric patients. However, in findings such as statistically significant increments of BMI and heart rate mean values, the variations over time in prolactin levels observed with risperidone and the differences between the two drugs remark the necessity of systematic monitoring.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice

“…A possible explanation for our findings could be that the standardized safety measuresincluding TDM with specialist diagnostic interpretation and recommendation -carried out as part of the study could have had a preventive effect on the development of serious ADRs under off-label conditions and could also have contributed to their most favorable course. In our study, a higher proportion of serious ADRs had a positive outcome than in the naturalistic studies cited above, in which (mostly non-serious) ADRs observed in youth during antipsychotic pharmacotherapy fully recovered in 27 % and improved in 24 % of cases [49], or fully recovered in 17.6 % and improved in 38.2 % of cases [50]. Unfortunately, no separate information about the outcome of serious ADRs was provided in either of these studies.…”

“…Another prospective study on the safety of antipsychotics in children and adolescents classified 10.1 % of the ADRs recorded under naturalistic conditions as serious, which were observed in 5.7 % of patients, and of which one third were psychiatric effects [75]. These authors point out, that concerning psychiatric ADRs, it is difficult to assign causality to psychotropic drugs with high reliability because of a potential worsening of the underlying condition and thus insufficient treatment effects [50]. The most common 'adverse event' in our study -'suicidality' -is at the same time a typical symptom of depression, which was the most frequent diagnosis in the sample and is known to be a strong risk factor for suicide [51].…”

Risperidone or Aripiprazole Can Resolve Autism Core Signs and Symptoms in Young Children: Case Study

“…Where possible, however, the use of methylphenidate or atomoxetine was avoided as these medications may add further to the potential burden of adverse effects and their use is off-label in very young children. The main side effects noted for risperidone and aripiprazole were weight gain (30%) and asymptomatic elevated prolactin (20%), which have been noted in previous studies [ 11 , 19 , 69 ].…”

Aripiprazole and Risperidone Present Comparable Long-Term Metabolic Profiles: Data From a Pragmatic Randomized Controlled Trial in Drug-Naïve First-Episode Psychosis

“…A recent large-scale systematic meta-review showed that both treatments presented an increased risk for weight gain in children and adolescents ( Solmi et al, 2020 ). In this regard, there has been an increase in evidence comparing the effects of these 2 antipsychotics on these populations in recent years ( Ishitobi et al, 2013 ; Wink et al, 2014 ; Nicol et al, 2018 ; Schoemakers et al, 2019 ; Cicala et al, 2020 ). Head-to-head comparison studies between aripiprazole and risperidone in these populations showed similar results on weight gain and lipid/glycemic parameters, in both the short term (6–12 weeks) ( Ishitobi et al, 2013 ; Nicol et al, 2018 ) and long-term (1 year) ( Wink et al, 2014 ; Schoemakers et al, 2019 ; Cicala et al, 2020 ).…”