What Role for Long-Acting Injectable Antipsychotics in Managing Schizophrenia Spectrum Disorders in Children and Adolescents? A Systematic Review

Abstract

Background Long-acting injectable antipsychotics (LAIAs) are an efficacious and well-tolerated treatment in adults with schizophrenia spectrum disorders (SSD). However, there is less evidence for their use in children and adolescents. Objectives The aim of this systematic review was to summarize findings regarding the effectiveness and side effects of LAIA in children and adolescents with SSD. Methods Four databases (Web of Science, PubMed, MEDES, and Dialnet) were systematically searched for articles published between inception and 12 March, 2022, with the following inclusion criteria: (1) original articles or case reports; (2) providing data on efficacy/effectiveness or safety/tolerability of LAIA treatment in children and adolescents diagnosed with SSD (schizophrenia, schizoaffective disorder, schizophreniform disorder, non-affective psychotic disorder); (3) mean age of samples ≤ 18 years; and (4) written in English or Spanish. Exclusion criteria were review articles, clinical guides, expert consensus as well as posters or oral communication in conferences. The risk of bias was assessed using the ROBIS tool. Results From 847 articles found, 13 met the inclusion criteria. These included seven single case reports or case series, four retrospective chart reviews, a 24-week open-label trial, and one observational prospective study, covering a total of 119 adolescents (aged 12–17 years) with SSD. Almost all the articles described data on second-generation LAIA (53 patients on risperidone [once every other week], 33 on paliperidone palmitate [once monthly], 10 on aripiprazole [once monthly], and two on olanzapine pamoate [once monthly]). Twenty-one patients were reported to be only on first-generation LAIAs. Non-adherence was the main reason for starting an LAIA. In all of the studies, the use of LAIAs was associated with improvement in the patients’ symptoms. Conclusions There are few studies assessing the use of LAIAs in adolescents with SSD. Overall, these treatments have suggested good effectiveness and acceptable safety and tolerability. However, we found no studies examining their use in children aged < 12 years. The problems and benefits linked to this type of antipsychotic formulation in the child and adolescent population require further study, ideally with prospective, controlled designs. Supplementary Information The online version contains supplementary material available at 10.1007/s40272-023-00558-x.

Comparison of long-acting injectable antipsychotics with oral antipsychotics and hospital readmission rates in pediatric patients

“…Only when the data was pooled for the entire 12 months of follow-up was there a significant difference with fewer readmissions in the LAIA group when compared with the oral comparator group. 6 …”

“… 2 When comparing schizophrenia spectrum disorders (SSD) in pediatric and adult patients, pediatric patients are reported to have worse outcomes linked to severe cognitive deficits, social impairment, relapses, and hospitalizations. 6 Whereas limited studies conclude that there may be improved clinical outcomes and adherence with using LAIAs when compared with oral counterparts, the lack of data supporting LAIA use in this population may lead to lower use of these formulations. 1 A meta-analysis of studies involving pediatric patients with SSD found clinical improvement of patients using LAIA formulations in up to 12 months of follow-up.…”

“… 1 A meta-analysis of studies involving pediatric patients with SSD found clinical improvement of patients using LAIA formulations in up to 12 months of follow-up. 6 A retrospective database analysis concluded that, although there is limited clinical data supporting the safety and efficacy of LAIAs in adolescents, their use in patients with documented nonadherence would be appropriate. 7 …”

“…However, there may be more benefit in using LAIA therapy earlier in pediatric patients to prevent poor prognoses in regard to relapse rates and hospitalizations. 6 Studies of LAIA formulations in adult populations often evaluate hospital readmission rates, but there are fewer studies in pediatric populations. 2 , 6 The objective of this study was to determine if the use of LAIA therapy in pediatric patients leads to a lower readmission rate when compared with oral AP therapy.…”

“… 6 Studies of LAIA formulations in adult populations often evaluate hospital readmission rates, but there are fewer studies in pediatric populations. 2 , 6 The objective of this study was to determine if the use of LAIA therapy in pediatric patients leads to a lower readmission rate when compared with oral AP therapy. This study may provide additional insight as there is limited evidence published on the beneficial use of LAIA therapy in pediatric patients.…”