Esketamine has demonstrated efficacy in treatment-resistant depression (TRD), but medium-term real-world functional outcomes remain understudied. This study described 6-month depressive symptoms and functional trajectories during routine esketamine treatment, focusing on functional outcomes and remission correlates.

In this prospective multicenter study, 60 patients with TRD initiating intranasal esketamine augmentation were assessed at baseline, Month 1, Month 3, and Month 6 using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS). Mixed-effects models, Turnbull interval-censored time-to-remission analysis, logistic regression, and ROC analyses were performed.

MADRS and SDS improved significantly at all follow-up time points (p < 0.001). At Month 6, symptomatic response and remission rates were 78.3 and 46.7%, while functional response and remission rates were 78.3 and 33.3%, respectively. Turnbull estimates showed cumulative functional remission rates of 5.0, 15.0, and 33.3% at Months 1, 3, and 6, respectively. MADRS-SDS correlations decreased over time, supporting partial symptomatic-functional dissociation. Higher baseline SDS (OR = 0.73, 95% CI: 0.59–0.89) and more previous antidepressant trials (ADTs; OR = 0.53, 95% CI: 0.35–0.82) were associated with lower odds of Month 6 functional remission; bootstrap internal validation supported coefficient stability. ROC-derived thresholds were considered sample-dependent and not clinically validated. Cumulative esketamine dosage was associated with functional response but not remission.

Depressive symptoms and functioning improved progressively over 6 months during esketamine treatment in routine clinical care. Functional remission followed a slower trajectory than symptomatic remission and had partly distinct correlates, supporting functional monitoring as a distinct TRD outcome.

This real-world study aimed to characterize patients with schizophrenia who achieve sustained good functional outcomes after antipsychotic discontinuation and to develop the Functional Remission in Schizophrenia after Antipsychotic Discontinuation (FURSAD) predictive model.

We retrospectively identified individuals aged 18–65 years with schizophrenia (ICD-10) from the Shanghai Mental Health Center discharge database. Patients who discontinued antipsychotics for ≥1 year were classified as functional remission (FR) or functional non-remission (FNR) based on functioning assessments. Sociodemographic, clinical, and treatment-related data were extracted blindly from hospital records and structured interviews.

Among 4,166 discharged patients screened, 180 met the inclusion criteria (FR: 116; FNR: 64). Six independent predictors were identified: total disease course, Clinical Global Impression-Severity (CGI-S) score, Positive and Negative Syndrome Scale (PANSS) emotional distress subscale score, use of first-generation antipsychotics, discontinuation due to treatment benefits, and discontinuation due to lack of insight. The logistic regression model showed strong predictive performance (AUC = 0.867, 95% CI 0.813–0.921), with 82.8% sensitivity and 81.9% specificity. Internal validation was performed via 10-fold cross-validation.

Discontinuation motives and illness trajectory are relevant in predicting long-term functional outcomes. A limitation is that a substantial number of patients could not be recontacted or declined participation, which may introduce selection bias. The FURSAD nomogram may help clinicians estimate the probability of FR 4.5 years post-antipsychotic discontinuation in patients previously on antipsychotics for ≥3 years.