Second-Generation Antipsychotics and Real-World Outcomes in Youth With On- and Off-Label Indications

Area of Science:

• Child and Adolescent Psychiatry
• Pharmacovigilance
• Real-world Evidence Studies

Background:

• Global increase in second-generation antipsychotic (SGA) prescriptions for youth.
• Limited understanding of SGA effects on real-world outcomes, particularly for non-approved indications.

Purpose of the Study:

• To evaluate the real-world outcomes of SGA treatment in a national cohort of youth.
• To examine changes in psychiatric hospitalization, self-harm, accidental injury, and violent crime risks before and after SGA initiation.

Main Methods:

• National cohort study of 21,306 youth (aged 7-17) in Sweden (2007-2020).
• Within-individual comparisons of risks one year before and after SGA initiation.
• Analysis of recurrent treatment up to 13 years, examining various indications including psychosis, ASD, and ADHD.

Main Results:

• Risks for psychiatric hospitalization, self-harm, and violent crime were elevated before SGA initiation and decreased during treatment, though not returning fully to baseline.
• Youth with psychosis-related disorders showed higher pre-initiation risks and subsequent decreases for hospitalization and self-harm.
• Neurodevelopmental disorders (e.g., ADHD) showed greater decreases in violent crime risk; accidental injury risk showed no significant association.

Conclusions:

• SGA treatment in youth is associated with a reduction in psychiatric hospitalization, self-harm, and violent crime risks after an initial escalation.
• Observed risk reductions during SGA treatment did not fully revert to pre-initiation levels.
• Accidental injury risk was not significantly associated with SGA treatment in this cohort.