Psychosis beginning during childhood or adolescence can disrupt education, relationships and the development of independence. Clinical decisions must consider both the consequences of untreated illness and the potential burden of treatment. Accurate diagnosis, careful interpretation of comparative drug evidence and attention to functioning are therefore inseparable. A review co-authored by Marinos Kyriakopoulos brings these priorities together, synthesising evidence on early-onset psychosis across diagnostic, prognostic and therapeutic domains (Salazar de Pablo et al., 2024). Its findings support active treatment while emphasising the limitations of a predominantly adolescent and methodologically heterogeneous evidence base.
Understanding the evidence base
Salazar de Pablo et al. (2024) included 30 meta-analyses, representing 373 individual studies and 25,983 participants, with a reported mean age of 15.1 years. The review examined epidemiology, biomarkers, cognition, prognosis, treatment response and adverse effects. This approach is valuable for clinical formulation: medication outcomes can be considered alongside the developmental and functional difficulties associated with illness. Early-onset psychosis refers to psychosis developing before age 18 and includes both affective and non-affective disorders. Early-onset schizophrenia is a more specific subgroup. Findings from schizophrenia trials cannot automatically be extended to every young person with psychotic symptoms, and evidence drawn mainly from adolescents provides less certainty for younger children. The review’s message is therefore best understood as support for specialised, developmentally informed care, with treatment decisions anchored to the clinical disorder being assessed (Salazar de Pablo et al., 2024).
Diagnostic precision before treatment selection
Psychotic experiences, established psychosis and schizophrenia should be distinguished. The review found that psychotic experiences were associated with subsequent psychotic disorders but also with non-psychotic mental disorders. Such experiences are clinically relevant without being diagnostically specific. Their presence should prompt careful assessment rather than an automatic schizophrenia diagnosis or an assumption that antipsychotic treatment is indicated. Clinical interpretation requires attention to the wider symptom pattern, duration, impairment and course (Salazar de Pablo et al., 2024). Diagnostic uncertainty is particularly consequential when mood symptoms coexist with psychosis. A clinically useful implication is to retain a longitudinal formulation: early labels may require revision as the relationship between mood episodes, psychotic symptoms and functioning becomes clearer. Reassessment should refine treatment rather than be interpreted as evidence that the initial presentation was unimportant. Cognitive and neurodevelopmental findings add context but do not provide an individual diagnostic marker. Young people with early-onset psychosis had difficulties in domains such as processing speed, attention and working memory. Neuroimaging differences were also identified at group level. The authors emphasise that validated approaches translating these findings into personalised clinical decisions remain underdeveloped. Accordingly, cognitive assessment may inform support needs, while biomarker findings should not be presented as tools that confirm psychosis in an individual child (Salazar de Pablo et al., 2024).
Antipsychotic efficacy and the limits of rankings
The pharmacological evidence supports antipsychotic efficacy for established early-onset psychotic disorders. The review reports improvements in total and positive symptoms, with smaller pooled effects on negative symptoms (Salazar de Pablo et al., 2024; Pagsberg et al., 2017). These results support considering several effective options, while recognising that short-term symptom outcomes cannot settle questions about long-term functioning, adherence or cumulative adverse effects. This distinction is especially important when discussing negative symptoms and cognition. Improvement on a total symptom scale does not demonstrate recovery of motivation, learning or social participation. The review identifies substantial cognitive difficulties and limited evidence addressing outcomes beyond psychotic symptoms. Clinically, treatment goals should therefore include meaningful functioning alongside symptom change, with explicit recognition that a favourable medication response may leave significant support needs unresolved (Salazar de Pablo et al., 2024).
Tolerability as a central treatment consideration
Adverse-effect profiles differ more clearly than efficacy for several commonly studied agents. Pagsberg et al. (2017) associated olanzapine particularly with weight gain, molindone with extrapyramidal symptoms and akathisia, and risperidone, paliperidone and olanzapine with increased prolactin. These findings make tolerability relevant at the point of treatment selection, rather than only after difficulties emerge. A medication’s clinical value depends on the benefits achieved and the burden experienced by the young person. The review similarly highlights metabolic effects, sedation, prolactin changes and movement-related adverse effects as important dimensions of treatment. Its clinical implication is that symptom improvement and physical health need to be reviewed together. A falling symptom score should not obscure weight gain or adverse effects that interfere with daily participation (Salazar de Pablo et al., 2024).
Treatment resistance and clozapine
Clozapine occupies a distinct position in the evidence. Salazar de Pablo et al. (2024) recommend considering it when early-onset psychosis is resistant to two other antipsychotics, with the strongest supporting evidence concerning treatment-resistant schizophrenia. Its superior efficacy in this context should not be translated into routine first-line use across the broader psychosis spectrum. The clinical question is whether the young person has persistent illness despite appropriate previous treatment, within a specialist assessment of treatment resistance. Adnan et al. (2022) found evidence supporting clozapine in childhood- and adolescent-onset schizophrenia, but also described important adverse effects, including sedation, hypersalivation, constipation, weight gain and haematological abnormalities. Their evidence base combined several study designs and remained limited. Thus, the case for access to clozapine is also a case for specialist expertise and structured safety monitoring. Potential benefit and monitoring requirements must be considered together, rather than allowing either to obscure the other.
Recovery and critical appraisal
Pharmacological treatment belongs within a broader recovery framework. A systematic review co-authored by Kyriakopoulos identified eight trials of psychological interventions, with some evidence of cognitive or psychosocial benefits but no significant effect on symptom reduction across the interventions examined (Anagnostopoulou et al., 2019). The limited evidence does not justify treating medication as sufficient for every outcome. Instead, it highlights the need to evaluate psychological, family and educational support using outcomes appropriate to their intended functions. The review’s limitations reinforce this caution. Primary studies overlapped across meta-analyses; outcomes were heterogeneous; some estimates lacked confidence intervals; and race and ethnicity were not adequately reported. Prognostic findings also require context: the reported 60.1% poor-outcome figure concerned early-onset schizophrenia, compared with 46.8% in samples with mixed early-onset psychoses, using functioning-based definitions over variable follow-up periods. These are group-level observations, not individual predictions or evidence that recovery is unattainable (Salazar de Pablo et al., 2024).
Conclusion
Evidence-informed management of psychosis in children and young people begins with diagnostic precision and continues through repeated evaluation of symptoms, functioning and treatment burden. The review by Salazar de Pablo et al. (2024) supports antipsychotic treatment for established illness and timely consideration of clozapine in treatment-resistant schizophrenia, while highlighting substantial uncertainty beyond short-term symptom outcomes. The clinical task is to integrate these findings into individual care: selecting treatment thoughtfully, addressing adverse effects, and maintaining developmental and functional goals. Better paediatric trials and longer-term follow-up are needed to establish which approaches most effectively support sustained recovery.
Where next?
Join us on 4 December 2026 for an expert half day conference on ‘Severe Mental Illness: Diagnosis, Pharmacological Management, and Monitoring’, with Dr. Marinos Kyriakopoulos and Professor Dr. Aditya Sharma.
Psychosis and bipolar disorder in children and young people can present significant challenges for clinicians, from reaching an accurate diagnosis to making informed decisions about pharmacological management and monitoring their ongoing impact.
This event brings together expert perspectives on the diagnosis and pharmacological management of these severe mental illnesses, with practical consideration of treatment monitoring, including the use of rating scales, physical health monitoring and the management of side effects.
References
- Adnan, M., Motiwala, F., Trivedi, C., Sultana, T., Mansuri, Z., & Jain, S. (2022). Clozapine for management of childhood and adolescent-onset schizophrenia: A systematic review and meta-analysis. Journal of Child and Adolescent Psychopharmacology, 32(1), 2–11. https://doi.org/10.1089/cap.2021.0092
- Anagnostopoulou, N., Kyriakopoulos, M., & Alba, A. (2019). Psychological interventions in psychosis in children and adolescents: A systematic review. European Child & Adolescent Psychiatry, 28(6), 735–746. https://doi.org/10.1007/s00787-018-1159-3
- Pagsberg, A. K., Tarp, S., Glintborg, D., Stenstrøm, A. D., Fink-Jensen, A., Correll, C. U., & Christensen, R. (2017). Acute antipsychotic treatment of children and adolescents with schizophrenia-spectrum disorders: A systematic review and network meta-analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 56(3), 191–202. https://doi.org/10.1016/j.jaac.2016.12.013
- Salazar de Pablo, G., Rodriguez, V., Besana, F., Civardi, S. C., Arienti, V., Maraña Garceo, L., Andrés-Camazón, P., Catalan, A., Rogdaki, M., Abbott, C., Kyriakopoulos, M., Fusar-Poli, P., Correll, C. U., & Arango, C. (2024). Umbrella review: Atlas of the meta-analytical evidence of early-onset psychosis. Journal of the American Academy of Child & Adolescent Psychiatry, 63(7), 684–697. https://doi.org/10.1016/j.jaac.2023.10.016