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Background The role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown. Study Design PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both groups. Random effects meta-analysis to evaluate (1) differences in DUP in early detection/intervention services vs the control group, (2) the efficacy of early detection strategies regarding eight real-world outcomes at baseline (service entry), and (3) the efficacy of early intervention strategies on ten real-world outcomes at follow-up. We conducted quality assessment, heterogeneity, publication bias, and meta-regression analyses (PROSPERO: CRD42020163640). Study Results From 6229 citations, 33 intervention studies were retrieved. The intervention group achieved a small DUP reduction (Hedges' g  = 0.168, 95% CI = 0.055–0.283) vs the control group. The early detection group had better functioning levels (g  = 0.281, 95% CI = 0.073–0.488) at baseline. Both groups did not differ regarding total psychopathology, admission rates, quality of life, positive/negative/depressive symptoms, and employment rates (P  > .05). Early interventions improved quality of life (g  = 0.600, 95% CI = 0.408–0.791), employment rates (g  = 0.427, 95% CI = 0.135–0.718), negative symptoms (g  = 0.417, 95% CI = 0.153–0.682), relapse rates (g  = 0.364, 95% CI = 0.117–0.612), admissions rates (g  = 0.335, 95% CI = 0.198–0.468), total psychopathology (g  = 0.298, 95% CI = 0.014–0.582), depressive symptoms (g  = 0.268, 95% CI = 0.008–0.528), and functioning (g  = 0.180, 95% CI = 0.065–0.295) at follow-up but not positive symptoms or remission (P  > .05). Conclusions Comparing interventions targeting DUP and control groups, the impact of early detection strategies on DUP and other correlates is limited. However, the impact of early intervention was significant regarding relevant outcomes, underscoring the importance of supporting early intervention services worldwide. [ABSTRACT FROM AUTHOR]

Objective To quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment. Methods We re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of "relapse-free" individuals by the end of follow-up (median = 118 days, IQR = 52.0–208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for >5 half-lives of the stabilizing antipsychotic, and studied predictors of "rebound psychosis" in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal. Results 29.9% (95%CI = 23.2–38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65–21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4–46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19–2.00), female sex (aHR = 1.37, 95%CI = 1.08–1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68–4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5–7.1). "Rebound psychosis" did not show predictors. Conclusions and relevance Our results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk. [ABSTRACT FROM AUTHOR]