Transition rates to schizophrenia and early intervention effectiveness in substance-induced and brief psychotic disorders: a randomized controlled trial.

This multisite, prospective randomized controlled trial examined transition rates to schizophrenia in individuals with recent-onset substance-induced psychotic disorder (SIPD) or brief psychotic disorder (BPD), and evaluated the efficacy of a specialized early intervention (SEI) designed to reduce this transition. We enrolled 1,000 participants (aged 16-40 years) across five Egyptian centers, randomly allocating them to SEI (n = 502) or treatment-as-usual (TAU; n = 498). TAU included standard antipsychotic treatment (primarily risperidone or haloperidol), monthly psychiatric follow-ups, and case management without structured psychosocial components. SEI combined monthly family psychoeducation, weekly cognitive-behavioral therapy, and low-dose risperidone (2 mg/day) with therapeutic drug monitoring. At 2-year follow-up, 26.3% of participants transitioned to schizophrenia. Transition rates were significantly higher in SIPD (29.1%) than in BPD (20.4%; HR = 1.48, p = 0.008), particularly among those with cannabis-associated SIPD (38.1%). SEI was associated with a 39% reduction in transition risk compared to TAU (HR = 0.61, p = 0.008). Key predictors included neurocognitive deficits (verbal learning OR = 0.79; working memory OR = 0.83), severe positive symptoms (OR = 1.15), and elevated inflammatory markers (CRP OR = 1.39). These findings suggest that SEI may reduce conversion, although causality cannot be definitively established. The study highlights the substantial risk of schizophrenia following a first psychotic episode, especially in the context of substance use. A comprehensive, multi-component early intervention appears effective in reducing transition rates, underscoring the importance of targeted preventive strategies.