From the Editor-in-Chief’s Desk: Long-Acting Injectable Antipsychotics

To Our Readers:

Since the development of the long-acting injectable (LAI) form of fluphenazine in 1966, LAIs have been refined to achieve more reliable outcomes, eventually becoming a mainstay in treatment guidelines for adults with schizophrenia and, more recently, bipolar disorder (Harlin et al., 2023; Meyer et al., 2024). Year after year, more evidence supports the efficacy, tolerability, and reliability of LAIs in maintenance therapy for adults with schizophrenia, schizoaffective disorder, and bipolar disorder (Correll et al., 2016; Pacchiarotti et al., 2019).

While LAIs have established their role in treating psychotic and severe mood disorders in adults, there is still much to understand about their use in children and adolescents. Contemporary research is limited, forcing clinicians to extrapolate from adult studies when considering side effects and pharmacodynamics.

The adage “children are not little adults” rings especially true for LAIs. Adolescents are in unique transitional periods developmentally, physically, and psychologically, and are at particular risk for developing chronic mental illness during this time. Despite the U.S. Food and Drug Administration approval of multiple oral atypical antipsychotic medications for youth, no long-acting injectable forms have been approved. This treatment gap is critical, as earlier onset of psychosis and bipolar disorder is associated with a steeper decline in clinical functioning. Structural changes in the brain may progress during untreated psychosis, with a similar decline seen in untreated bipolar disorder.

Introducing LAIs early in the course of schizophrenia may enhance adherence, reduce relapse rates, lower hospitalization rates, and improve overall prognosis. These potential benefits are further underscored by crucial developmental processes occurring during adolescence, such as frontal lobe development, increasing independence, formation of intimate relationships, and the development of abstract thought.

Despite the theoretical benefits of early LAI introduction, current evidence remains mixed. Much of the literature focuses on highly symptomatic, high-risk, often hospitalized, non-adherent populations. There are many unanswered questions related to the use of LAI antipsychotic treatment in youth. What diagnoses are most appropriate for LAI use, particularly among youth with autism and aggression where oral medications may have limitations relating to administration and adherence? What dosing guidelines are most suitable for youth? At what stage in treatment should LAIs be considered? These questions need urgent addressing, and future research is essential.

This special issue seeks to continue inquiry, dialogue, and efforts to establish an evidence base for LAI antipsychotic treatments in youth. Dr. Alexander M. Scharko and colleagues are pioneers in this topic through ongoing clinical experience and a systematic review in this issue. Their review identified 30 studies, and a survey of clinicians provided more information (Scharko et al., 2024a). This article identifies important opportunities to improve the rigor of research focused on LAI antipsychotic treatment for youth.

This review is followed by two contributions from Dr. Christina Sun and colleagues. One study examined 45 unique pediatric patients commencing treatment with an LAI antipsychotic. Notably, the majority of the patients were male, and Black or African American treated for schizophrenic spectrum illnesses or bipolar disorder (Sun et al., 2024a). The results were encouraging with respect to clinical outcome but highlighted the need for controlled studies. While a follow-up study did not demonstrate statistically significant benefits with pragmatic outcomes such as psychiatric hospitalizations and days hospitalized, there was numeric improvement in the outcomes after the initiation of LAI treatment (Sun et al., 2024b).

An intriguing Dr. Parinda Parikh and colleagues present real-world data from a sample (N = 116) of adolescents treated with LAI antipsychotics for bipolar disorder or schizoaffective disorder, bipolar type. Descriptive data suggested steady improvements in Young Mania Rating Scale assessments over 1 year. The majority (86.2%) of patients in the sample were able to transition back to school. The most common side effects included increased appetite, weight gain, restlessness, and extrapyramidal symptoms. This descriptive study supports the need for future randomized controlled trials and inferential approaches (Parikh et al., 2025).

We round out the special issue with a letter describing the use of the LAI aripiprazole lauroxil to treat an adolescent with autism spectrum disorder (Scharko and Mireski, 2024b) and another letter with one group’s experience developing a clinical pathway for the use of LAI antipsychotic medication to treat youth (Scharko et al., 2024c). This month, Garzon and colleagues present data from the largest maintenance study to date of transcranial magnetic stimulation for adolescents with treatment-resistant depression (Garzon et al., 2024). This study is another example of a long-term treatment approach with a different modality and patient population.

We hope you enjoy this issue of the Journal of Child and Adolescent Psychopharmacology.