Extrapyramidal symptoms as early clinical predictors in first-episode schizophrenia and schizophreniform disorder: findings from the OPTiMiSE trial

Extrapyramidal symptoms (EPS) may occur as a primary feature in patients with first-episode psychosis with no or brief exposure to antipsychotics (AP). We aimed to analyse the prevalence of EPS in naïve and quasi-naïve first episode schizophrenia spectrum disorders (FES), their demographic and clinical correlates at baseline, and their association with clinical outcomes during follow-up. We analysed data from the OPTiMiSE trial, Phase 1 (n = 481 participants with FES, aged 18-40). The presence of EPS was defined as a score on the neurological side effects subscale of the UKU ≥ 1. We compared groups with and without baseline EPS in demographic, clinical and functional measures, and performed logistic and linear regressions models to analyse the associations between baseline EPS and clinical outcomes at follow-up. The prevalence of EPS at baseline was 30 % and was higher in women. There were no differences between AP-naïve or quasi-naïve participants. Participants with EPS showed a higher rate of depressive symptoms and suicidality at baseline. The fully adjusted models showed an association between the presence of EPS at baseline and more severe depressive, positive, negative, general and total symptoms, increased suicidality, and poorer subjective wellbeing and functionality at follow-up. Our findings support EPS as a primary feature of schizophrenia and suggest that early onset EPS (after no or minimal AP exposure) may point to a FES subgroup with poorer clinical prognosis. This suggests the role of EPS as an early marker of poor outcome, with the potential to guide targeted interventions in FES.