Polysubstance use linked to symptoms after psychosis remission

INTRODUCTION: Substance use is common among patients with a first episode of psychosis (FEP). While long-term studies link substance use to poorer outcomes, short-term associations, particularly involving polysubstance use, remain understudied. This study examined substance use patterns 3 to 6 months after remission and their associations with symptoms, cognition, and functioning. METHODS: Data were derived from the HAMLETT randomized controlled trial, which compared continuation versus early discontinuation of antipsychotic medication following remission, using assessments at baseline, 3, and 6 months. Substance use patterns were categorized as no substance use, tobacco use, tobacco plus cannabis use, or polysubstance use (i.e. tobacco, cannabis and other illicit drugs). Associations with psychotic symptoms (PANSS), cognition (BACS, Stroop), and functioning (WHODAS 2.0) were examined using linear mixed-effects models adjusted for age, sex, education, alcohol use, and randomization condition. RESULTS: Of 379 FEP patients, 283 were included in the analyses: 161 reported no substance use, 83 tobacco use, 26 tobacco plus cannabis use, and 13 polysubstance use. Substance use patterns remained stable over six months. Polysubstance use was associated with more severe positive symptoms compared to other substance use groups and poorer self-care, compared to patients who do not use substances. Differences in positive symptoms were primarily observed in patients continuing antipsychotic medication, suggesting that positive symptoms reflect substance use-related clinical differences. CONCLUSION: Polysubstance use represents a risk profile in the early post-remission phase of FEP, characterized by elevated positive symptoms and functional impairment in self-care, suggesting early disruption of daily functioning during the post-remission phase.