This systematic review and meta-analysis examined the trajectory of antipsychotic efficacy over time in children and adolescents (ages 8–19) with schizophrenia, using 14 double-masked RCTs (n=3,115) identified from searches through January 2025. It also tested whether lack of early improvement (<20% symptom reduction at 2 weeks) predicts non-response and non-remission at endpoint.
Antipsychotic effects accumulated rapidly from week 1 (SMD −0.15) to week 4 (SMD −0.46), with diminishing returns thereafter (week 6: −0.55; week 8: −0.57). Lack of early improvement at 2 weeks predicted non-response with 82% specificity and 91% PPV, and non-remission with 68% specificity and 76% PPV.
- The sample was 65% White, limiting generalizability to other ethnic groups. - Only 14 RCTs were included, and individual patient-level data were not used, which may limit the precision of predictive estimates. - The analysis pools across different antipsychotic agents, potentially masking drug-specific differences in response trajectories.
In pediatric schizophrenia, most antipsychotic benefit appears within the first 4 weeks — clinicians should assess meaningful symptom change by week 2, as failure to achieve ≥20% improvement at that point is a strong signal (91% PPV) that the patient is unlikely to respond. Consider re-evaluating the treatment plan early rather than waiting for a full trial to conclude.
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