Short-, Medium-, and Long-Term Cardiometabolic Outcomes in First-Episode Psychosis: A Systematic Review and...

Individuals with first-episode psychosis (FEP) experience increased cardiometabolic risks, contributing to reduced life expectancy. While metabolic disturbances are well described in chronic schizophrenia, their trajectory from first presentation, before or with minimal antipsychotic exposure, through to long-term follow-up remains incompletely characterized.

To synthesize evidence on progression of cardiometabolic outcomes in FEP cohorts from before initiation of antipsychotic medication to up to 10 years of follow-up.

Following PRISMA and MOOSE guidelines (PROSPERO: CRD42023431072), Medline, Embase, PsycInfo, and CINAHL+ were searched to July 2025 for studies of FEP cohorts with ≤28 days of antipsychotic exposure at baseline. Outcomes included weight, glucose, lipids, blood pressure, metabolic syndrome (MetS), diabetes, and cardiovascular disease (CVD). Random-effects meta-analyses were stratified by follow-up duration. As post-baseline exposure was not quantified, follow-up estimates reflect outcomes under routine care.

From 2601 unique articles, 82 studies were included. Obesity and MetS prevalence increased from 5.4% and 8.5%, respectively at baseline, to 26.6% and 18.2% at 1-3 years, whereas type 2 diabetes increased from 0.5% to 5.0% by >5 years. Lipid abnormalities emerged early, while blood pressure changes were minimal, and CVD hospitalization prevalence was 1.4% at 5-10 years. Weight increased by +2.5 kg at 4-8 weeks and + 13.4 kg at >5 years, with parallel increases in BMI and waist circumference.

Cardiometabolic deterioration begins within weeks of FEP onset and accumulates over time, indicating the need for early prevention, sustained monitoring, integrated metabolic care, and patient education throughout the course of care.