While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms.

To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs).

PubMed, PsycInfo, Cochrane Library, and Embase were systematically searched from database inception through November 7, 2025, with no language limits.

Randomized clinical trials (RCTs) with (1) diagnosis of an MDE; (2) intervention and comparator groups consisting of intravenous ketamine and controls (eg, saline or midazolam); and (3) suicidal and depressive symptoms as efficacy outcomes were included.

Hedges g standardized mean differences (SMDs) were used to analyze improvement in suicidal and depressive symptoms using random-effects models. Multiple subgroup analyses were also conducted.

The main outcomes included the following: (1) changes in suicidal and depressive symptoms; (2) response and remission rates of depressive symptoms; and (3) safety measures (eg, adverse events and serious adverse events).

A total of 26 RCTs comprising 1166 patients with an MDE (n = 626 receiving ketamine and n = 540 as control patients) were included. For suicidal symptoms, patients receiving a single ketamine infusion, compared with control patients, had significantly lower symptoms at 24 hours (SMD, -0.69 [95% CI, -0.98 to -0.40]) and at 1 month (SMD, -0.70 [95% CI, -1.17 to -0.24]). Those with repeated ketamine infusions showed a similar reduction of suicidal symptoms at the end of the treatment (SMD, -0.72 [95% CI, -1.00 to -0.43]). For depressive symptoms, significant reductions were shown at 4 hours (SMD, -1.74 [95% CI, -2.43 to -1.06]), 24 hours (SMD, -1.15 [95% CI, -1.58 to -0.72]), 3 days (SMD, -0.97 [95% CI, -1.73 to -0.20]), and 1 week (SMD, -0.89 [95% CI, -1.65 to -0.13]) after a single ketamine infusion and at the end of the treatment after repeated infusions (SMD, -0.81 [95% CI, -1.16 to -0.46]). Reported serious adverse events (eg, hospitalizations and deaths) were unrelated to the interventions, and other adverse events (eg, headache) were transient and resolved during the trials.

The findings of this systematic review and meta-analysis suggest that single and repeated intravenous ketamine infusions are efficacious in reducing suicidal and depressive symptoms in patients with an MDE in the acute phase, while longer-term outcomes are not well established.

The effectiveness of pharmacogenetics to guide prescribing of selective serotonin reuptake inhibitors (SSRIs) for depression remains unclear, despite the well-established association between SSRI pharmacokinetics and genetic variation.

To determine whether pharmacogenetic-guided prescribing of SSRIs improves treatment response in patients with depression.

The ADOPT PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) Depression pragmatic randomized clinical trial was conducted from August 10, 2021, through April 27, 2024, at primary care, psychiatry, or family medicine clinics at enrolling sites throughout the US. Patients were aged 8 years or older and had experienced depression for 3 months or longer.

Patients were randomized to genotype-guided SSRI prescribing (intervention group) or usual care (control group). Actionable drug metabolism phenotypes were defined as those for which pharmacogenetic clinical guidelines recommend alternative medication selection or dose adjustment.

The primary outcome was change in Patient-Reported Outcomes Measurement Information System (PROMIS) depression T scores at 3 months among patients with the actionable phenotype. Secondary end points included adverse effect severity of SSRIs at 3 months and depression remission (measured with PROMIS depression scores and Patient Health Questionnaire-8 [PHQ-8] scores) at 6 months.

This study of 1460 patients included 1239 adults (84.9%) (mean [SD] age, 40.6 [16.7] years) and 221 children (15.1%) (mean [SD] age, 14.6 [1.8] years). Most patients were female (1096 [75.1%]). A total of 692 patients (47.4%) had an actionable phenotype; 351 (50.7%) were assigned to the intervention, and 341 (49.3%) were assigned to usual care. At baseline, 463 of the 692 patients (66.9%) reported having depressive symptoms for more than 2 years, 603 (87.1%) were receiving pharmacologic treatment, and 354 (51.2%) were receiving nonpharmacologic treatment. At 3 months, no significant differences were observed between the intervention and usual care groups in change in PROMIS depression T scores (mean [SD] change, -4.3 [8.4] vs -4.0 [8.1]; P = .68), medication adverse effect burden (mean [SD] change, 8.2 [4.3] vs 7.8 [4.5]; P = .37), or Patient Health Questionnaire-8 score change (mean [SD] change, -3.3 [5.2] vs -2.7 [4.8]; P  = .13). However, at 6 months, the PROMIS depression T-score remission rate (score ≤16) was higher in the intervention group compared with the usual care group (153 of 317 patients [48.3%] vs 122 of 310 patients [39.4%]; P = .02).

In this randomized clinical trial, genotype-guided prescribing of SSRIs did not improve control of depression symptoms at 3 months compared with usual care but was associated with higher depression remission rates at 6 months. These findings suggest a possible longer-term clinical benefit and indicate that future studies should focus on the durability and long-term impact of genotype-guided prescribing in the management of depressive symptoms.

ClinicalTrials.gov Identifiers: NCT04445792 (Master Protocol Research Program platform trial) and NCT05966155 (ADOPT PGx Depression trial).

Most adults living with major depressive disorder (MDD) fail to achieve remission with conventional antidepressants. The US Food and Drug Administration (FDA) has approved 5 atypical antipsychotics in MDD on the basis of their substantial evidence of efficacy and safety.

To compare the efficacy and acceptability of FDA-approved atypical antipsychotics for the adjunctive treatment of MDD in order to provide decision support to practitioners and persons with lived experience.

A systematic search was conducted using PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase from database inception through July 15, 2025.

Six independent raters screened publications for eligibility. Inclusion criteria were atypical antipsychotics that are FDA approved in the adjunctive treatment of MDD.

Two independent raters obtained data and examined risk of bias in accordance with the Cochrane criteria. Effect sizes were synthesized using random-effects models. Data were analyzed from August to September 2025.

The primary outcomes were efficacy (ie, ≥50% reduction from baseline in the total Montgomery-Åsberg Depression Rating Scale [MADRS] score) and acceptability (ie, all-cause discontinuation).

A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes.

This systematic review and meta-analysis indicates that differences exist between adjunctive atypical antipsychotics in the treatment of MDD with respect to overall efficacy and acceptability, which should be simultaneously considered. The absence of adequate and well-controlled studies documenting maintenance efficacy of adjunctive atypical antipsychotics in MDD remains a knowledge gap.

This study examines factors associated with park visits, physical activity (PA), and chronic health conditions using baseline data from a cluster randomized controlled trial to promote PA and park visits among churchgoing Latino adults in low-income urban communities. Participants (n = 726) were recruited from 12 Catholic churches in predominantly Latino neighborhoods in and near East Los Angeles. Data collection included accelerometer-measured PA, self-reported weekly park visits, socio-demographics, history of hypertension and Type 2 diabetes, family and friend social support for PA, depression (PHQ8), stress, and measured height and weight. Multivariable linear and logistic regression models assessed associations between predictors and health outcomes. The average age was 52.3 years; 76% were women; 71% had completed high school or less; and the average BMI was 31.1 (obese). Age, female gender, and higher depressive symptoms were negatively associated with moderate-to-vigorous PA (MVPA). Being employed, greater depressive symptoms, and more safety concerns were negatively associated with park visits, while higher family support for PA was positively associated. Both accelerometer-based MVPA and self-reported park visits were associated with lower depressive symptoms. Park visits were also associated with lower odds of Type 2 diabetes, and higher family support for PA was linked with reduced odds of hypertension. These results address gaps in understanding the relationships between PA and park visits and physical and mental health among churchgoing Latino adults. Churches may serve as important venues to support family-oriented park events and promote greater use of parks for health promotion in Latino communities. Association of park visits, physical activity and health outcomes among Latino church members in low-income urban communities.Clinical trial registration number NCT03858868; 2019-02-27.

Muscle weakness is a common impairment following neurological disorders, yet traditional high-load training aimed at addressing this is often impractical or unsafe for these patients. Blood flow restriction (BFR) training has emerged as a viable method, capable of eliciting physiological adaptations comparable to high-load training while using significantly lower mechanical loads.

This study aimed to summarize the clinical applications of BFR training for neurological disorders and assess its effectiveness and safety in improving muscle strength and functional outcomes.

The systematic review and meta-analysis followed PRISMA guidelines. PubMed, Embase, PEDro, Cochrane, CINAHL, CNKI were searched for intervention studies comparing BFR with diverse control interventions. The primary outcomes were muscle strength and functional outcomes. Sensitivity analyses, subgroup analysis and meta-regression were also performed.

Thirty-seven studies involving 963 participants were included, with individuals having stroke (n = 639), Parkinson's disease (n = 18), multiple sclerosis (n = 128), spinal cord injury (n = 170), cerebral palsy (n = 1), peripheral nerve injury (n = 2), and transverse myelitis (n = 1). Our results revealed that the addition of BFR significantly increased muscle strength, with effect sizes of 0.752 (95% CI 0.49-1.02). Significant improvements were also observed in balance, Fugl-Meyer Lower Extremity assessment, and Modified Barthel Index. Subgroup analyses revealed that onset time was a crucial factor for the effectiveness of BFR on clinical outcomes. Furthermore, BFR training demonstrated overall safety in neurological rehabilitation.

These findings support the effectiveness of BFR training in improving muscle strength and functional outcomes in neurological rehabilitation, without any significant adverse events. However, further high-quality research is needed to validate the efficacy of BFR and refine its training protocols for individuals with neurological disorders.

Posttraumatic stress disorder (PTSD) is a mental health condition with widespread effects on mental and physical health and mortality. In this paper, we present the current state of research on the epidemiology of PTSD, including its prevalence, risk factors, and impact. The U.S. lifetime prevalence of PTSD is estimated to be 6.1%-8.3%, and the global prevalence is estimated at 3.9%. PTSD prevalence has been consistently found to be higher among certain subgroups, including women and military veterans. Risk factors for PTSD include pretrauma variables, preexisting mental health conditions, sociodemographic characteristics, and features of the traumatic event itself. Consequences of PTSD include effects on psychiatric comorbidity, physical health conditions, and all-cause and cause-specific mortality. Points of consideration and challenges affecting the study of PTSD epidemiology are noted, including debates on specifying a trauma criterion for diagnosis, the validity of complex PTSD as a diagnosis, and the dearth of recent population-based longitudinal data to understand this disorder. Suggestions for future research and clinical implications are discussed.

Background: Adverse childhood experiences (ACEs) disproportionately affect women and significantly increase the risk of postpartum post-traumatic stress disorder (PTSD). However, the psychological mechanisms underlying this relationship remain inadequately investigated.Aim: To develop a constructivist grounded theory explaining how ACEs influence the development of postpartum PTSD.Methods: Employing a constructivist grounded theory approach, this qualitative study was conducted at a tertiary hospital in South China between November 2023 and October 2024. Data were collected through in-depth interviews conducted with 10 women who experienced ACEs and subsequently developed postpartum PTSD. Early maladaptive schemas (EMS) were identified as the central construct in the resulting theory.Results: The developed theory contains five components: (1) the origin of EMS; (2) the formation of EMS; (3) the trigger of EMS; (4) the operation of EMS; and (5) the outcome of EMS. Findings suggest that ACEs were perceived as providing the foundation for EMS, which gradually solidified during an individual's developmental trajectory to become an ingrained subconscious framework for responding to external stressors. During the stress-inducing event of childbirth, EMS appeared to be activated, influencing cognitive appraisals of the stressor, coping strategies, and perceived social support, ultimately contributing to the experience of postpartum PTSD symptoms.Conclusion: This study advances a constructivist grounded theory that elucidates how ACEs relate to the development of postpartum PTSD within the context of the formation, activation, and operationalisation of EMS. Given the modifiable nature of EMS, these findings highlight the potential of targeted interventions like schema therapy and trauma-informed care. Effective maternal support should address both the immediate stress of childbirth and the persisting influence of ACEs.

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by persistent avoidant/restrictive eating unrelated to body image. Sex differences in clinical phenotypes and neurobiology of ARFID are understudied. We hypothesized that females with ARFID would have a greater frequency of the lack of interest and fear of aversive consequences phenotypes, higher levels of anorexigenic hormones, and greater fMRI activation in brain regions associated with cognitive control during a food cue paradigm. We further hypothesized that males with ARFID would have a greater frequency of the sensory sensitivity profile, higher levels of orexigenic hormones, and greater fMRI activation in reward processing brain regions.

We recruited 96 children and adolescents with ARFID and sub-threshold ARFID (49% female) from two studies on the neurobiology of ARFID and low weight eating disorders from 2016 to 2022. We analyzed ARFID clinical phenotypes; appetite-regulating hormones, ghrelin, cholecystokinin (CCK), peptide YY (PYY), and oxytocin; and fMRI activation of cognitive control and reward-related brain regions during a food cue paradigm using frequentist and Bayesian statistical analysis.

Contrary to our hypothesis, there were no sex differences in frequency of ARFID clinical phenotypes, appetite-regulating hormone levels, or brain activation.

This is the first study to provide empirical evidence that ARFID has a similar clinical and neurobiological presentation in males and females.

This paper systematically reviews the literature on levels of eco-emotions reported by young adults (aged 18-29) across nations, with meta-analyses of associations between eco-anxiety and mental health outcomes. Fourteen databases were searched for relevant studies. Fifty-nine studies reported levels of eco-emotions, with 37 studies reporting associations between eco-anxiety and each of anxiety, depression, and stress. Eco-anxiety was the most reported eco-emotion. Higher scores of eco-anxiety and eco-fear were reported by populations facing direct environmental impacts. Eco-anger and eco-hope were reported to have a role in adaptive coping. Meta-analyses indicated moderate, significant positive associations between eco-anxiety and depression r = 0.29, anxiety r = 0.34, and stress r = 0.30. Meta-regressions were conducted to explore heterogeneity. Our results highlight the importance of addressing heterogeneity in operationalizing the construct of eco-anxiety and the need to collect data on eco-emotions in low-and-middle-income nations, which is lacking in the current literature.