Ketamine has shown rapid antidepressant effects in treatment-resistant mood disorders; however, the durability of these benefits during maintenance treatment remains unclear. This systematic review evaluated outcomes associated with repeated ketamine and esketamine administration during the maintenance phase of treatment. A systematic search of PubMed, Ovid, and Scopus was conducted from database inception through March 2026. Studies involving more than 8 treatments or more than 1 month of treatment in individuals with mood disorders were included. Eligible designs consisted of randomized controlled trials, open-label studies, observational cohorts, and case series. A total of 43 studies met inclusion criteria, including randomized controlled trials and extension studies (n = 8), open-label studies (n = 4), observational studies (n = 24), and case series (n = 7). Overall, ketamine and esketamine were associated with sustained clinical improvement during ongoing treatment, although outcomes varied across study designs. Randomized trials demonstrated reduced relapse rates with continued treatment, while relapse was common following discontinuation of treatment. Observational studies showed heterogeneous outcomes, with evidence of both sustained improvement and attenuation of benefit over time. Case series reported mixed durability. These findings suggest that continued treatment may be important for preserving therapeutic benefit, although long-term outcomes are not uniform across individuals. Further research is needed to optimize maintenance strategies, identify predictors of sustained response, and clarify the long-term efficacy and safety of ketamine-based therapies for mood disorders.
Quality of life (QoL) in older adults with major psychiatric disorders is affected by various clinical and social factors, yet longitudinal evidence on QoL determinants remains limited. This study tests a comprehensive model of predictors of QoL using structural equation modelling (SEM).We analysed data from the Cohort of individuals with Schizophrenia Aged 55 years or more (CSA) study, a multicenter cohort of older adults diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, recruited from 63 French psychiatric centers. QoL was assessed using the Quality-of-Life Scale (QLS) at baseline and follow-up (median = 3.0 years, SD = 1.44). We examined the simultaneous effects on QLS at follow-up of six predictor groups assessed at baseline, including (1) severity of general psychopathology, (2) severity of depressive symptoms, (3) severity of cognitive impairment, (4) psychotropic medications, (5) general medical conditions, and (6) sociodemographic characteristics.Six predictors showed significant independent longitudinal associations with QoL. Lower QoL was associated with greater depressive symptoms (β=-0.225), greater cognitive impairment (β=-0.117), antipsychotic polypharmacy (β=-0.538) and longer follow-up (β=-0.330) (all p-values<0.05). In contrast, higher baseline QoL (β=0.401) and greater levels of general psychopathology (β=0.291) were positively associated with follow-up QoL.Depression, cognitive impairment and antipsychotic polypharmacy emerged as markers of poorer QoL, independently of baseline QoL and diagnosis, although the association with depression was not robust in sensitivity analyses. The unexpected positive association with psychopathology is compatible with statistical suppression, measurement overlap, survival bias and limited illness awareness rather than a true benefit of symptoms.
Verbal learning develops substantially during adolescence and is consistently impaired in schizophrenia. Despite the severity of cognitive deficits in early-onset schizophrenia (EOS), verbal learning has not been systematically examined in adolescent patients. Understanding these impairments is essential due to their impact on academic, social, and functional outcomes. Methods 106 adolescents (12–17 years) with schizophrenia or schizophreniform disorder (DSM-5) were recruited from inpatient and outpatient services in Mexico City. Assessments included the MINI-KID, Hopkins Verbal Learning Test–Revised (HVLT-R), and Positive and Negative Syndrome Scale (PANSS). Descriptive analyzes, repeated-measures ANOVA, Cochran’s Q test, and Pearson correlations were used to evaluate verbal learning performance and its associations with symptoms. Results Participants showed incremental learning across HVLT-R trials but low overall performance, recalling on average seven of 36 words. Intrusions and perseverations were infrequent yet related to poorer recall. Total correct words correlated negatively with negative symptoms, while semantic intrusions correlated positively with positive symptoms. Associations among HVLT-R variables indicated deficits in encoding, organization, and retrieval. Conclusions Adolescents with schizophrenia exhibit significant verbal learning deficits linked to both negative, positive and general psychopathology symptoms. Early identification of these impairments is crucial for guiding targeted cognitive interventions. Larger, controlled studies are needed to refine these findings and support culturally relevant assessment and rehabilitation strategies.
Background Adapted physical activity (APA) may benefit patients with schizophrenia (SZPs), but neurobiological effects remain underexplored. We investigated whether a 16-week web-based APA program (e-APA) induces brain plasticity in SZPs and whether brain changes relate to cardiorespiratory fitness and clinical symptoms. Methods In secondary analyses of a randomized controlled trial, 31 SZPs were assigned to e-APA (n = 16) or e-health education (e-HE, n = 15), matched to 23 healthy controls (HCs). Structural and resting-state functional MRI were acquired pre- and post-intervention to assess cortical surface area, thickness, and functional connectivity (FC). Relationships with VO2max and symptom changes were examined. Results Compared to SZPs-HE, SZPs-APA showed greater surface area changes in the left superior frontal, right precentral and right cuneus cortices. Separately, within SZPs-APA, VO2max improvement was associated with changes in the left precentral and inferior temporal cortices and right insula, while reductions in apathy and positive symptoms were associated with changes in the right fusiform, rostral middle frontal, inferior temporal cortices and left supramarginal cortex. Greater FC changes within the frontoparietal network (FPN) were observed in e-APA versus e-HE, and within the default-mode network in SZPs-APA versus SZPs-HE, at the uncorrected level (neither survived multiple-comparison correction). FPN changes were associated with VO2max gains. No significant structural and functional differences occurred between SZPs-APA and HCs-APA. Conclusions e-APA induced cortical plasticity in motor, visual, and associative regions in SZPs. Brain changes were associated with improvements in cardiorespiratory fitness and clinical symptoms, while uncorrected FC findings require cautious interpretation. e-APA may represent a promising adjunct to the treatment of schizophrenia.
