Long-Acting Injectable Antipsychotics vs. Oral Antipsychotics for Schizophrenia Relapse Prevention in Young Adults

Abstract

Introduction: Schizophrenia onset often occurs in late adolescence or early adulthood, a period associated with poor medication adherence. Long-acting injectable antipsychotics (LAIs) may reduce relapse risk compared to oral antipsychotics (OAs), but evidence specifically in young adults (18–30 years) is limited.

Methods: Systematic review and meta-analysis of RCTs and high-quality cohort studies comparing LAIs to OAs in young adults with schizophrenia or schizoaffective disorder. Primary outcome: relapse (psychiatric hospitalization, symptom exacerbation requiring treatment escalation). Secondary: all-cause discontinuation, extrapyramidal symptoms (EPS). Databases: MEDLINE, Embase, PsycINFO. Random-effects meta-analysis.

Results: Nine studies (n=2,431 young adults) met inclusion: 5 RCTs, 4 prospective cohorts. LAIs significantly reduced relapse risk compared to OAs (risk ratio [RR] 0.62, 95% CI 0.49–0.78, p<0.001). Number needed to treat to prevent one relapse was 8. All-cause discontinuation did not differ (RR 0.94, 0.81–1.09). EPS were more frequent with LAIs (RR 1.32, 95% CI 1.05–1.66). Second-generation LAIs (paliperidone, aripiprazole) had lower EPS rates than first-generation (haloperidol decanoate). Mortality and metabolic syndrome did not differ.

Discussion: LAIs reduce relapse in young adults with schizophrenia, likely due to assured adherence rather than superior efficacy. The EPS signal is concerning but mitigated by second-generation agents. Limitations include short follow-up (median 12 months) and exclusion of first-episode psychosis in most trials.

Conclusions: Long-acting injectable antipsychotics should be considered for young adults with schizophrenia and prior adherence difficulties. Second-generation LAIs are preferred due to better tolerability. Shared decision-making should address injection acceptance.