Influence of Age and Gender on Short-Term Efficacy, Acceptability and Safety of Antipsychotic Drug Treatment of Adolescents With Schizophrenia

OBJECTIVE: To investigate whether age or gender moderates short-term antipsychotic efficacy, acceptability, or safety in adolescents with early-onset schizophrenia (EOS).

METHOD: We analyzed data from four placebo-controlled randomized registration trials of antipsychotics in EOS (2003-2015). An individual patient data meta-analysis (IPDMA) evaluated how age and gender affected efficacy (PANSS total change, response), acceptability (all-cause discontinuations), and safety (adverse event incidence). Covariates included age at onset, body mass index, baseline negative symptoms, and study year.

PROSPERO ID: CRD42024572863.

RESULTS: We included 949 adolescents (61% boys, 39% girls; mean age=15.4 years). Neither age (β=0,251, 95% CI -1,561 to 2,064) nor gender (β=3,057, 95% CI -0,206 to 8,175) significantly altered overall antipsychotic efficacy on mean PANSS improvement or response rate. All-cause discontinuation was likewise unaffected. Younger adolescents on active medication showed a higher incidence of adverse events than those on placebo, whereas older adolescents exhibited similarly low rates across arms (correlation coefficient=-0,272, p<0,001). Gender did not significantly influence adverse-event incidence (aggregate β=0,037, p=0,832). The overall correlation coefficient -0,131 (p=0,342) between age and five major side-effect classes (weight gain, extrapyramidal side effects, QTc prolongation, prolactin increase, sedation) suggested no meaningful age impact, with ORs ranging from 0,858 (p=0,691) for weight gain to 1,244 (p=0,225) for sedation.

CONCLUSION: Younger adolescents demonstrated greater vulnerability to antipsychotic-related adverse events despite exhibiting comparable efficacy and acceptability to older adolescents. These findings suggest that age-based dosing and monitoring may be warranted when treating adolescents with EOS.