Sex differences in schizophrenia outcomes have been reported, with women often showing better long-term outcomes than men. However, the impact of Early Intervention Services (EIS) on these sex differences remains under-researched. Prior studies exploring short- and long-term sex differences in FEP patients have yielded mixed results, potentially due to design biases or shorter follow-up periods. Some studies indicate better functional outcomes for women in the initial years of EIS, while others highlight the influence of premorbid factors and age of onset. The current study aimed to comprehensively explore long-term sex differences in multiple outcome measures (clinical, functional, cognitive, treatment) among FEP patients after discharge from an EIS, hypothesizing that outcomes would be similar for men and women after approximately 10 years.

Existing research on sex differences in schizophrenia outcomes is inconsistent. While some studies suggest women experience better disease courses and outcomes, others indicate that these advantages diminish over time, converging with male outcomes. Factors such as age at illness onset, premorbid adjustment, and social support have been proposed to explain these discrepancies. Studies examining the long-term impact of EIS on sex differences in FEP patients are limited, hindering a complete understanding of the issue. The heterogeneity in functional outcomes among FEP patients and the potential for selection bias in studies focusing on patients with poor outcomes further complicate the interpretation of findings.

This study employed a 10-year follow-up design using data from the PAFIP (Programa de Atención a la Fase Inicial de la Psicosis) cohort and its 10-year extension, PAFIP-10. The study initially enrolled 307 FEP patients between 2001 and 2008, providing 3 years of EIS. At the 10-year follow-up (2014-2018), 209 patients (95 women, 114 men) were reassessed. Data collected included sociodemographic variables, clinical symptoms (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Scale for Schizophrenia [CDSS]), functioning (Disability Assessment Schedule [DAS]), cognition (Global Cognitive Function [GCF]), antipsychotic medication dosage (converted to chlorpromazine equivalents), and extrapyramidal symptoms (Simpson-Angus Scale). Statistical analyses included t-tests, chi-squares, repeated measures ANCOVAs, and Kaplan-Meier survival analysis.

At baseline, women were older at illness onset and admission, had higher premorbid functioning, IQ, and education levels, and were more often employed, living independently, and in partnerships. Men were more likely to have a schizophrenia diagnosis and to use cannabis and alcohol. During the first 3 years of EIS, women demonstrated better response to lower antipsychotic dosages and higher recovery rates (50% vs. 30.8%). At the 10-year follow-up, women continued to live independently and had more partners, while men still showed higher rates of schizophrenia, cannabis use, and tobacco use. Women exhibited less severe negative symptoms, but functional recovery differences were not statistically significant (46.7% vs. 34.4%). Both men and women experienced an increase in antipsychotic dosage after EIS discharge. Relapse rates were similar between sexes, with most relapses occurring in the first 3 years. Positive symptoms improved similarly in both groups; however, negative symptoms improved more significantly in women.

The findings suggest that the initial better outcomes for women during the first 3 years of EIS were associated with more favorable premorbid characteristics and baseline factors. The convergence of outcomes at the 10-year mark, except for negative symptoms, highlights the importance of factors beyond the initial EIS intervention. The increase in antipsychotic medication after discharge from the EIS program for both sexes raises concerns about long-term treatment strategies. The persistence of differences in negative symptoms between sexes warrants further investigation into potential biological, psychosocial, and environmental factors. The study's limitations include the use of the DAS (an outdated measure of functioning) and potential information bias.

This study provides valuable long-term data on sex differences in FEP outcomes after EIS. While women initially exhibited better outcomes, these advantages largely disappeared after 10 years. Increased antipsychotic medication after discharge from EIS suggests the need for sex-specific treatment strategies and potentially extended EIS interventions. Future research should investigate the interplay of biological, psychosocial, and environmental factors in shaping these long-term outcomes and explore more robust functional outcome measures.

The study's limitations include the use of an outdated measure of functioning (DAS), the potential for information bias due to reliance on retrospective data and incomplete follow-up, and the lack of exploration of the relative contributions of biological, psychosocial, and environmental factors. The relatively small sample size also reduces statistical power, especially in subgroup analyses. Further, the study was conducted in a specific geographic region and may not be fully generalizable to other populations.