BMJ Mental Health

Background: Observational studies have consistently reported associations between social media use (SMU) and poorer mental health outcomes; however, such designs cannot establish causality. This study synthesised evidence from randomized experiments to estimate the effects of restricting SMU on mental health outcomes. Methods: A systematic search was conducted across MEDLINE, Embase, PsycINFO, and Cochrane CENTRAL to identify experimental trials evaluating interventions that constrained SMU for at least 24 hours and included an unconstrained control condition. Multilevel random-effects meta-analyses were used to synthesise effect estimates. Prespecified meta-regressions explored study-level moderators, and population-level impact fractions were estimated relative to global SMU prevalence. Results: From 7,784 screened records, 37 reports representing 35 distinct studies were included (pooled N = 7,160). Most interventions lasted one to three weeks and targeted college-aged youth. Pooled estimates favoured SMU constraints across outcomes, with magnitude and precision varying by domain. Confidence intervals were entirely above zero, consistent with a beneficial response for depressive symptoms (g = 0.22; 95% CI, 0.12 to 0.32), perceived stress (g = 0.15; 95% CI, 0.01 to 0.29), anxiety symptoms (g = 0.19; 95% CI, 0.05 to 0.34), fear of missing out/nomophobia (g = 0.14; 95% CI, 0.04 to 0.24), and well-being (g = 0.36; 95% CI, 0.10 to 0.63). Heterogeneity was substantial for several outcomes (I2 > 75%). In bivariate meta-regressions, higher baseline SMU was associated with larger effects for anxiety symptoms ({beta} = 0.13; 95% CI, 0.03 to 0.22), and longer interventions were associated with larger effects for depressive symptoms ({beta} = 0.16; 95% CI, 0.02 to 0.30). Inferences revealed that a short-term reduction in SMU globally could plausibly mitigate 17.5% and 15.4% of depressive and anxiety symptom cases, respectively. Conclusions: Experimental design-based evidence supports the causal case for an effect of SMU on mental health, with constraints producing improvements across multiple outcomes and no evidence of harm. Population-level inferences suggest that even individually modest effects may translate into meaningful public health benefits given the high prevalence of SMU exposure. These findings suggest that reducing SMU may represent a low-intensity, low-cost, scalable strategy to support mental health and improve well-being.

Background Autistic people experience disproportionately high rates of co-occurring mental illness and suicide, yet mental healthcare services routinely fail to meet their needs. Patients unrecognised as autistic are at risk of ineffective or harmful treatment. Autistic psychiatrists occupy a unique position: as members of both medical and autistic communities, they offer dual insider perspectives that may directly shape patient outcomes. Despite being the second largest specialty group in Autistic Doctors International (ADI), this workforce remains largely unrecognised and underutilised. This study examines autistic psychiatrists' perspectives on mental healthcare for autistic people. Methods Loosely structured interviews were conducted with seven senior autistic psychiatrists across child and adolescent, adult, and liaison psychiatry, recruited from a psychiatry-specific subgroup of ADI. Data were analysed using reflexive thematic analysis: codes related to patient care and mental health services were extracted and analysed as a focused subset. Outcomes Nine themes were identified: autistic-to-autistic therapeutic rapport; benefit of recognition and diagnosis; early recognition and education as preventive factors; iatrogenic harm from non-recognition and systemic pathways to misdiagnosis; knowledge gaps and stereotypes; inaccessible services; resource constraints and diagnostic thresholds; autistic psychiatrists as an underutilised resource; and pathways to change. Interpretation Autistic psychiatrists' dual insider positionality affords a unique and under-acknowledged vantage point on what autistic patients experience and where mental healthcare fails them. The mental health burden autistic people carry is substantially shaped by systems not designed for them. Embedding neurodiversity-affirmative practice, closing training gaps, reforming diagnostic pathways, and recognising autistic psychiatrists as a clinical and epistemic resource offer a coherent pathway to improving mental health outcomes for autistic people.

Depression is accompanied by considerable comorbidity and excess mortality. We examined multimorbidity data using the validated pharmacy-based Rx-Risk Comorbidity Index and examined healthcare costs associated with chronic illness burden in the Australian Genetics of Depression Study (AGDS). Australian Pharmaceutical Benefits Scheme (PBS) record linkage for 15,890 AGDS participants was available from 01/07/2013-31/12/2017. Forty-six health morbidities were inferred by mapping the prescription data using Anatomical Therapeutic Chemical Classification System codes and PBS Item Codes. Morbidity prevalence rates were then compared with an unselected 10% Australian representative population sample (10PCT) with PBS claims data available from 01/07/2010-31/12/2014. The average number of inferred comorbidities was higher among AGDS participants (4.6 {+/-} 2.9) than 10PCT individuals (3.0 {+/-} 3.0). Excluding depression, 89.1% of AGDS participants had one or more inferred comorbidity, most commonly pain (51.0%), inflammation/pain (40.3%), and anxiety (32.3%). In the AGDS, the number of comorbidities was higher among women compared to men and positively correlated with participant age, BMI, number of depressive episodes experienced, and annual health care costs. Compared to participants with no inferred comorbidities, the median annual health care costs were ~65% higher among those with 2-3 comorbidities. This study highlights the patterns of health morbidities experienced by individuals living with depression and shows that this chronic disease burden is significantly associated with increased health costs to the individual and the health system.

Mental illness poses a substantial global burden, yet existing psychotherapies and psychopharmacologies often produce limited outcomes. Psychedelic assisted therapies have emerged as potential transdiagnostic interventions. In particular, 3,4 methylenedioxymethamphetamine assisted therapy (MDMA AT) has generated interest for its rapid psychological effects and potential to enhance psychotherapy outcomes. However, the incremental efficacy of MDMA AT relative to control interventions across transdiagnostic outcomes remains unclear. Further, there have been emerging concerns regarding harm reporting quality in MDMA AT clinical trials. We conducted a systematic review and meta analysis of MDMA AT randomized controlled trials. Eleven publications representing eight controlled trials with 10 analyzed subgroups (n = 295 participants) were included in meta-analyses. Two additional secondary publications were included for harm reporting syntheses (k = 13 total). Across 114 extracted effect sizes, MDMA AT demonstrated a significant moderate-to-large incremental reduction in psychopathology relative to controls (g = 1.03, 95% CI [0.46, 1.60]), though heterogeneity was high (I squared = 76%). Incremental effects were larger versus inert placebos (g = 1.27) than active controls (g = 0.75). Symptom specific analyses indicated strong incremental effects for trauma reduction (g=1.46 [95% CI: 0.67, 2.25]) and smaller non-significant effects for depression (g=0.51 [95% CI: -0.06, 1.08]). Harm reporting quality synthesis showed only 23% of publications met high-quality reporting standards. Overall, MDMA AT demonstrates potential transdiagnostic efficacy, but small samples, confounding factors, and mediocre harm reporting highlight the need for larger more transparent clinical trials.

Objective: Neuropsychiatric presentations are common across neurological and mental health services but they are often inadequately covered by core clinical psychology and clinical neuropsychology training. Consequently, we aimed to identify components for a neuropsychiatry curriculum for clinical psychologists using a Delphi process. Method: We completed a three-round e-Delphi study with 19 experts (clinical psychologists, neuropsychologists, psychiatrists, neurologists, individuals with lived experience of neuropsychiatric disorders). Round 1 collected ratings on 80 syllabus items derived from textbook reviews, conference topics, and a scoping review of neuropsychiatry syllabuses. Items failing to reach consensus were refined, and new topics added via free-text suggestions. Rounds 2 and 3 repeated rating and thematic analysis, culminating in a consensus meeting where items were classified as core or supplementary. Consensus thresholds were set at mean>=2.0, mean distance from the mean<=0.2, and => 75% agreement for final decisions. Results: The process yielded 40 core and 38 supplementary syllabus items. Core topics include autoimmune and neuroinflammatory disorders, delirium, functional neurological disorders, neuropsychiatric sequelae of epilepsy, stroke, traumatic brain injury, dementia, and multidisciplinary working, among others. Supplementary items covered background knowledge of less frequent but still prevalent disorders as well as competencies in interpreting clinical data alongside conceptual and historical issues. The final component list reflects both clinical competencies and emerging areas of practice, emphasising assessment, formulation, psychological interventions, cultural considerations, and medicolegal aspects. Conclusions: The e-Delphi derived curriculum provides a framework for neuropsychiatric competencies for postgraduate psychology training with modification needed for application in diverse healthcare settings.

Background Escalating mental health service demands have created a need to better identify young people most likely to require continued support from mental health services at the transition between childhood and adulthood. Anxiety is the most common adolescent mental health condition, yet its clinical significance and prognosis are not well understood. We aimed to examine the risk of young adult-onset psychiatric disorders in individuals with an adolescent anxiety disorder, and identify stratifiers of risk of subsequent psychiatric disorders in this group. Methods Individuals from the Norwegian Mother, Father, and Child Cohort Study (MoBa) with linked health records and aged 18 or over as of the 31st December 2023 were included. Those diagnosed with any ICD-10 anxiety disorder when aged 10-17 years were defined as having an adolescent anxiety disorder (n=2107, controls n=47,582). Polygenic scores (PGS) for psychiatric and neurodevelopmental conditions were calculated using LDpred2. Anxiety, comorbidities, and parental psychiatric history were defined through linked ICD-10 diagnoses. Sex was defined through linked records. Individuals were defined as having a young adult-onset psychiatric disorder if they first received any new psychiatric diagnosis aged 18-24. Results Adolescent anxiety diagnosis was associated with increased risk of all adult-onset psychiatric disorders (HR= 2.33-8.65). Post-traumatic stress disorder PGS, parental history of severe mental illness, and female sex were associated with increased risk of transition to a young adult-onset psychiatric disorder in people with an adolescent anxiety disorder. Conclusions Adolescent anxiety greatly increases the risk of a psychiatric disorder during the transition to adult life. Clinicians should consider female sex and parental psychiatric history when prioritising young people with anxiety for adult mental health service support. Future research needs to further consider whether polygenic scores would aid risk stratification in clinical practice.

Background: Participants in the ReINVEST randomised placebo-controlled trial of sertraline, conducted among men with high trait impulsivity and histories of violent offending, received structured clinical contact throughout the trial, including psychiatric assessments, nursing consultations, crisis support, and referrals to mental health and external services. We estimated the effect of placebo trial participation, compared with non-participation after baseline and single-blind run-in, on violent and domestic-violence reoffending. Methods: This prespecified secondary analysis included men from the ReINVEST trial pathway who completed baseline assessment and entered the single-blind run-in phase but did not proceed to randomisation, to inform the counterfactual. Violent and domestic-violence offences were identified from linked administrative records over 12- and 24-month follow-up periods. The adjusted difference in offending was estimated using two independent analytical approaches accounting for baseline differences. Additional analyses examined whether the effect varied by baseline clinical and criminal-history characteristics, whether pre-randomisation external referrals explained selection into placebo participation, and whether post-randomisation external referrals accounted for any part of the estimated effect. Results: Placebo trial participation was associated with lower offending across both outcome domains and follow-up periods. Placebo-standardised mean count differences for violent offending were -0.19 (95% confidence interval [CI] -0.38, -0.04) at 12 months and -0.22 (95% CI -0.51, -0.05) at 24 months. Corresponding differences for domestic-violence offending were -0.37 (95% CI -0.81, -0.14) at 12 months and -0.49 (95% CI -0.92, -0.22) at 24 months. The association was more apparent among men with a documented psychiatric history and, for domestic-violence offending, among those with higher baseline anger, irritability and aggression. Pre-randomisation referrals did not explain selection into placebo participation or materially alter the estimates. Post-randomisation referrals were observed in both groups, remained more common in the placebo group, and did not account for the observed association. Conclusion: Placebo participation in this trial involved sustained clinical contact and psychosocial support beyond exposure to inactive medication, and these non-pharmacological components may have contributed to lower reoffending. In placebo-controlled trials involving populations with high psychiatric morbidity and limited continuity of coordinated care, the clinical content of placebo participation should be explicitly characterised in trial design and interpretation.

Background: While growing enthusiasm for the therapeutic potential of classic psychedelics has led to a rise in non-clinical use, attention to persisting adverse effects has emerged with delay. A subset of individuals reports persisting complications such as hallucinogen persisting perception disorder (HPPD), depersonalization/derealization disorder (DDD), anxiety and depression. Yet few medical services are equipped to address these complications. Aims: This qualitative study examines how societal, medical, and media discourses shape the experiences of individuals with persisting psychedelic-related complications, focusing on help-seeking trajectories. Methods: Thirteen semi-structured interviews with adults experiencing persisting psychedelic-related psychological symptoms (four women, nine men, age 19-49 years; HPPD (n = 10), DDD (n = 6), depression (n = 1), and anxiety (n = 1)) were conducted within a larger study on these complications. Data were analysed using reflexive thematic analysis. Reporting followed the COREQ guidelines. Results: Three interrelated themes emerged: (1) The dissonance between expectation and harm - idealised media and scientific portrayals of psychedelics shaped initial use and complicated recognition of adverse outcomes; (2) Stigma, silence, and self-blame - prohibitionist discourse and internalised shame significantly inhibited help-seeking; and (3) Between systemic absence and self-organised support - participants encountered clinical unpreparedness and epistemic dismissal, which often led them to rely on online peer communities and self-management strategies. Positive clinical encounters, characterised by professional expertise and nonjudgmental engagement, were experienced as helpful. Conclusions: Adequate clinical and conceptual frameworks for persisting psychedelic-related complications are lacking. An interdisciplinary, experience-informed approach integrating realistic risk communication, clinician training, and destigmatisation is required to support affected individuals.

Introduction: Engagement with mental health services (MHCS) during the first episode of psychosis (FEP) is critical for symptom control, quality of life, and relapse prevention. However, disengagement rates remain high in Uganda with severe consequences for patients and caregivers. This study protocol describes a mixed-methods investigation which aims to examine the relationship between patients and caregivers lived experiences and mental health service engagement during first-episode psychosis. Methods and Analysis. The mixed-methods study will recruit 82 patients with first-episode psychosis and their primary caregivers from Butabika National Referral Mental Hospital in Kampala, Uganda. Inclusion criteria are ages 18-60, less than 12 weeks on antipsychotic medications, living in the greater Kampala Metropolitan Area, with a consenting caregiver. Caregivers must be an adult (> 18years) providing full-time care for at least 6 months prior. Patients with substance use disorders will be excluded. Qualitative data on the lived experiences of patients and caregivers will be collected using the draw-write-and-tell method, while quantitative data on service engagement and associated factors will be collected using semi-structured questionnaires. The data will be analysed using Stata version 18, and participants will be reimbursed for their time. Ethics and Dissemination. Ethical clearance has been obtained from the School of Medicine Research and Ethics Committee (SOMREC) Ref: Mak-SOMREC-2024-1002 and institutional approval from Butabiika National Referral Mental Hospital. All participants will provide informed consent prior to participation. Data will be de-identified and securely stored, with results disseminated through peer-reviewed academic publications, conferences and community stakeholder workshops.

Background Little is known about the provision of diagnoses to young people with mental health disorders. We investigated diagnosis provision by NHS mental health services, focusing on 17-year-olds in South London between 2009-2024, and compared with estimated disorder prevalence. Methods To examine diagnosis provision in the population, we extracted diagnosis data from records of the NHS mental healthcare provider serving South London, using the Maudsley Biomedical Research Centre Clinical Record Interactive Search application; we then compared these data with the corresponding population size, obtained from the Office for National Statistics. To assess diagnosis provision in those with mental health disorders, we compared diagnosis data with the number of young people estimated to have met criteria for a disorder, derived from epidemiological interview data collected in the Environmental Risk (E-Risk) Longitudinal Twin Study and weighted according to characteristics of 17-year-old South Londoners. To assess diagnosis provision in those with mental health disorders within health services, we compared diagnosis data with the number estimated to have met criteria for a disorder and used any health service for their mental health, again derived from weighted E-Risk Study data. Findings Of 17-year-olds from South London in 2009-2024, 4.0% (n=8,958/223,404) had a diagnosis in mental health records during the previous year. This diagnosis provision covered <1 in 16 of those estimated to have had a mental health disorder, and <1 in 4 of those estimated to have also used health services. Diagnosis provision was lower in girls than boys and in young people with Black/Asian/Mixed/Other ethnicity than those with White ethnicity, in those estimated to have had a mental health disorder and used health services. Interpretation These findings demonstrate gaps and biases in mental health diagnosis provision for young people, including within health services, and reveal the imperative need to strengthen young people's mental healthcare.

Background. There is growing evidence to suggest a clinically significant overlap between autism spectrum conditions and psychotic disorders. Preliminary evidence suggest that autism diagnoses and autistic traits are associated with poorer outcomes following a first episode of psychosis. Methods. This study used data from the Cambridgeshire and Peterborough National Health Service Foundation Trust (CPFT) Research Database to examine clinical outcomes in autistic and non-autistic people following a first episode of psychosis. We describe patterns of community and inpatient service use, using descriptive statistics , Cox regression, binomial logistic regression, and negative binomial regression. Results. Data from 282 autistic and 7127 non-autistic people with psychosis were analysed. Autism was associated with greater community service use (use of mental health emergency lines, mental health detentions by police), as well as greater likelihood of psychiatric hospital admission (adjusted hazard ratio 1.34, 95% confidence interval 1.05 -1.7, p<0.05) and longer inpatient stays (median 111 versus 48 days, p<0.0001). Learning disability played a significant role in the utilisation of community and inpatient services, with lower rates of community service use but longer inpatient admissions. Conclusions. This study indicates a differing pattern of service use between autistic and non-autistic people following psychosis that warrants further research into how best to support autistic people with psychosis.

Background Treatment guidelines for borderline personality disorder (BPD) recommend assessment, diagnosis, and psychoeducation. We report on the feasibility and safety of a randomized controlled trial protocol of online psychoeducation, assessment, and personalized feedback as an immediate first step of care for BPD. Methods Newly diagnosed participants were randomized to receive 10 videos about BPD or general mental health for two weeks. Half the participants receiving BPD videos were randomized to receive personalized feedback on changes in symptom ratings and cognitive performance. Ecological momentary assessment (EMA) evaluated interpersonal interactions, emotions, and behaviors for 30 days. BPD symptoms, depression, and personality functioning were assessed at baseline, after videos, after feedback, and one month later. Results Eighty-two participants were randomized into three conditions that did not differ significantly in terms of demographics or baseline variables. Dropout occurred for 32.9% of the sample. No differences in rate of emergency room visits, hospitalizations, or other escalations in level of care were reported among groups. Satisfaction was higher for those receiving psychoeducational videos about BPD. Improvement in BPD knowledge in the psychoeducation conditions was significantly greater than the control condition. No statistically significant differences were found regarding reduction of BPD symptoms. The psychoeducation with feedback arm showed significantly greater improvements in self-impairment compared to controls with medium effect size at the final timepoint. Modeling of the relationship between time spent alone and BPD symptoms showed a positive correlation in the control condition, but in the group receiving both psychoeducation about BPD and feedback, this relationship was negative. Conclusion Online psychoeducational videos and assessment were safe, feasible, and acceptable to participants with newly diagnosed BPD. Psychoeducation with personalized feedback appears to be more effective than either BPD or general psychoeducation alone in improving deficits in self-functioning, which may relate to an increased capacity to be alone with fewer symptoms. The protocol was registered with ClinicalTrials.gov (NCT05358925, https://clinicaltrials.gov/study/NCT05358925) on April 28th, 2022.

Importance: The menopausal transition is associated with an increased risk of depression. Prior depression is a well-established risk factor, but studies do not distinguish between prior reproductive and non-reproductive depression. Objective: To compare the associations of reproductive (i.e., premenstrual mood disorder and perinatal depression) and non-reproductive (i.e., not related to hormonal transitions) histories of depression with depressive symptoms during the menopausal transition. Design: Cross-sectional analysis of questionnaire data from the Multidisciplinary Menopausal Outpatient Care Project (MOPP) collected between February 2023 and October 2025. Setting: Menopause outpatient clinics Amsterdam, the Netherlands, including a specialized multidisciplinary menopause clinic. Participants: In total 364 individuals were approached; 244 enrolled at baseline. After exclusions for age <40 (n=3), premature ovarian insufficiency (n=2), premenopausal status (n=1), age >58 with final menstruation >10 years earlier (n=12), bipolar disorder (n=5), and missing survey data (n=41), 180 participants were included. Exposures: Premenstrual mood disorder measured with Premenstrual Symptom Screening Tool, perinatal depression with Edinburgh Postnatal Depression Scale Lifetime version, and reported prior non-reproductive depression in medical records. Main outcome and measures: Depressive symptom severity measured with Inventory of Depressive Symptomatology-Self Rated. We used univariable and multivariable linear regressions; multivariable models accounted for overlap between exposures. Results: Among 180 participants (median age 51; 61% perimenopausal and 39% postmenopausal), premenstrual mood disorder showed the strongest association with depressive symptom severity (B = 9.0, 95% CI 5.1-12.9, p < 0.001), followed by perinatal depression (B = 7.8, 95% CI 3.4-12.1, p < 0.001) and prior non-reproductive depression (B = 4.7, 95% CI 0.7-8.7, p = 0.021). In multivariable analysis, only premenstrual mood disorder (B = 7.2, 95% CI 2.4-12.1, p = 0.0037) and perinatal depression (B = 5.7, 95% CI 1.2-10.1, p = 0.013) remained associated with depressive symptom severity. Conclusions and Relevance: Prior reproductive depression, but not prior non-reproductive depression, was associated with greater depressive symptom severity during the menopausal transition. A history of premenstrual mood disorder and/or perinatal depression may therefore help identify individuals at increased vulnerability to depressive symptoms during this period. Future studies should replicate these findings in population-based samples.

Aim: Schema Therapy (ST) is an evidence-based treatment for complex mental health problems rooted in early Adverse Childhood Experiences (ACEs). Although both individual and group formats have shown effectiveness, little is known about which format works best for whom. This question is particularly relevant for adolescents given their unique developmental needs. Despite over a decade of clinical experience with ST in adolescents, current research offers limited guidance on how to tailor the format to individual needs - resulting in a persistent gap between research and practice. This study aims to develop practice-based indication criteria for individual versus group schema therapy by integrating therapists expertise with experiences from adolescents who underwent ST. Methods: This qualitative study employs a constructivist Grounded Theory approach. Data will be gathered through focus group discussions with schema therapists and individual interviews with adolescents. Therapists will be purposively selected based on experience with both therapy formats and with traumatized adolescents. Adolescents are eligible if they have experienced ACEs and have completed at least 20 sessions of ST. Results: The analysis will result in a theoretical model that integrates therapists clinical reasoning and adolescents preferences. Conclusions: This study integrates schema therapists expertise and adolescents lived experiences to develop actionable indication criteria for choosing between individual and group ST. By supporting informed clinical decision-making, the findings contribute to treatment personalization in adolescent ST and address key challenges such as suboptimal outcomes and treatment dropout. Moreover, the identified criteria provide a foundation for future quantitative validation.

Objectives To explore caregiver and clinicians perspectives on implementing mental health conversations and supports for caregivers of children with chronic conditions in paediatric outpatient clinics. Specifically, views were sought on (a) screening approaches and measures (phase 1) and (b) how feedback and support could be provided to caregivers experiencing mental health difficulties (phase 2). Methods Caregivers and clinicians from two outpatient clinics (neuromuscular and diabetes) at a tertiary paediatric hospital in Melbourne, Australia participated in online focus groups in July and August 2024. Caregivers were recruited from outpatient clinics and clinicians were recruited via email. Both groups were combined for phase 1 before separating into breakout rooms for phase 2. Two authors conducted reflexive thematic analysis of transcripts using NVivo. Results Sixteen participants (caregivers n = 8; and clinicians n = 8) took part in in two semi-structured focus groups. Analysis generated two overarching domains, each comprising multiple themes. Domain 1, Addressing caregiver mental health, captured themes of overwhelm and invisibility, diverse caregiving roles, and the need for time and resources to support wellbeing conversations. Domain 2, Housing the mental health conversation, encompassed themes of screening preferences, caregiver agency in confidentiality, delivery of feedback, and access to tailored supports. Conclusions Caregivers and clinicians support routine caregiver mental health discussions in paediatric outpatient settings. Caregivers favour screening at diagnosis and key transitions, with clear, and actionable feedback delivered away from the child. Questions about record-keeping warrant further exploration, as do the perspectives of fathers.

Structured AbstractO_ST_ABSBackgroundC_ST_ABSPost-Traumatic Stress Disorder (PTSD) is a mental health condition affecting people who experience traumatic events. Trauma-exposed occupational groups report higher rates of PTSD than the general population. Current treatments, and access, often take months and may cause distress when people are required to talk about the trauma. ObjectiveTo determine the proof of concept of FIRST, a brief, non-trauma focussed therapy, in two separate populations with employment-associated PTSD. MethodTwo independent, single-arm, experimental therapy pilot trials were conducted. Trial one recruited 20 military veterans who received FIRST therapy via trained third-sector therapists. Trial two recruited 16 health and social care workers with FIRST therapy delivered by healthcare provider therapists. All participants were adults with PTSD (confirmed via CAPS-5 in trial one, and symptom score of [&ge;]33 on the PCL5 in trial two). Primary outcomes were recruitment feasibility, retention, data quality and reduction in PTSD symptoms. Secondary outcomes were anxiety and depression symptoms, daily life functioning and perceived health status. Veterans were followed up at 12 weeks post-enrolment and healthcare workers at 8 weeks. ResultsThe veteran trial progression criteria to main trial were met. Seventy-nine people screened eligible, 43 attended a CAPS-5 assessment; 20 had confirmed PTSD and were enrolled. Seventeen completed therapy and 12-week outcome measures. Mean PCL-5 scores decreased from 48.7 (SD = 13.02, n=20) at baseline to 23.5 (SD = 15.30, n=17) at 12-weeks. The healthcare worker trial obtained informed consent from 16 participants, 10 commenced therapy and were included in analysis with eight completing therapy. Mean PCL-5 scores decreased from 42.60 (12.23, (n=10) at baseline to 22.00 (19.92, n=8) at 8-weeks. ConclusionsProof of concept of FIRST was established. PTSD symptom reductions exceeded the PCL-5 minimal clinically important difference. Undertaking a fully powered randomised controlled trial of FIRST therapy is feasible within both healthcare and third sectors. HighlightsO_LIPost-traumatic stress disorder (PTSD) is more common in military veterans and health workers than the general population C_LIO_LITherapy can be challenging to commence and complete when it requires a focus on the trauma incident C_LIO_LIFIRST offers a promising, brief, non-trauma focused therapy for the treatment of PTSD C_LI

Background: Generalized anxiety disorder (GAD) is associated with substantial psychological burden, autonomic dysregulation, and limitations of existing pharmacological and psychotherapeutic treatments. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-invasive neuromodulation approach, but evidence regarding home-based application in GAD remains limited. Objective: To evaluate the feasibility, safety, and preliminary clinical and physiological outcomes of a home-based taVNS intervention in adults with psychologist-confirmed moderate-to-severe GAD. Methods: In this prospective single-arm feasibility study, 48 participants initiated a 4-week home-based taVNS intervention consisting of two daily stimulation sessions performed five days per week. Clinical assessments were conducted at baseline, Week 2, Week 4, and follow-up visits at Weeks 6 and 8. Ambulatory electrocardiographic monitoring was performed before treatment initiation, at Week 2, and at the end of treatment to assess heart rate variability (HRV) using the root mean square of successive differences (RMSSD). Primary outcomes included feasibility, safety, adherence, and change in clinician-rated anxiety severity (HAM-A). Results: Thirty-four participants completed the study and were included in the primary analyses. HAM-A scores decreased significantly from baseline to Week 4 ([EMD] -6.9, 95% CI -10.4 to -3.4, p = 0.001), with partial maintenance during follow-up. Improvements were also observed in Beck Anxiety Inventory scores, whereas changes in GAD-7, perceived stress, depressive symptoms, and sleep quality were not statistically significant. RMSSD increased significantly from baseline to Week 4 (EMD 6.7 ms, 95% CI 2.1-11.3, p = 0.009). Greater increases in RMSSD were associated with larger reductions in HAM-A (R^2 = 0.18, p = 0.031) and BAI scores (R^2 = 0.21, p = 0.019). No serious adverse events occurred. Mean adherence was 79.8%, and 73.5% of participants completed at least 70% of prescribed stimulation sessions. Conclusions: Home-based taVNS was feasible and generally well tolerated in adults with moderate-to-severe GAD. Preliminary improvements in clinician-rated anxiety severity and autonomic physiological measures were observed; however, the single-arm design precludes causal inference. These findings support further evaluation of home-based taVNS in adequately powered randomized sham-controlled trials.

Background: The incidence of antidepressant withdrawal reactions in longer-term users and the influence of dosage is insufficiently understood. Objectives: Informed by neuropharmacological models and user surveys, this study examined symptom change during tapering and if increases were specifically associated with reductions below 75% of the minimum effective dose. Design: This was a prospective longitudinal cohort study with seven assessments over six months. Methods: Altogether 32 Swiss adult primary care patients who were on antidepressants for at least six months and in stable remission were assessed at baseline (week 0) before they started tapering and after 2, 4, 6, 8, 16, and 26 weeks. Withdrawal symptoms were measured repeatedly using an adapted version of the Discontinuation-Emergent Signs and Symptoms Scale (DESS) and the main outcome was intra-individual symptom change during intervals. Antidepressant dose was standardized relative to the minimum effective dose in the treatment of depressive and anxiety disorders. Results: Across intervals, reductions below 75% of the minimum effective dose were associated with symptom increases, while reductions above that threshold or no reductions were associated with symptom decreases. After adjusting for potential confounders, the rate of clinically relevant symptom increases contingent on dose reductions below 75% of the minimum effective dose was 33%, as compared to 13% during intervals with no dose reductions (OR=3.2, 1.4 to 7.4). We thus estimated that 60% of the risk of clinically relevant symptom increases was attributable to pharmacological withdrawal effects. The adjusted incidence rates for clinically relevant and severe withdrawal reactions were 32% and 11%, respectively. Conclusions: Consistent with neuropharmacological research findings, we found that antidepressant withdrawal symptoms emerge mostly following reductions below 75% of the minimum effective dose, affecting about one-third of patients. Even small reductions may trigger clinically relevant withdrawal reactions in this lowest dose-range, stressing the need for personalized tapering plans.

Introduction Functional neurological disorder (FND) is a common cause of neurological disability and is associated with substantial healthcare utilisation and cost. Most available treatments target specific symptom subtypes, and prospective evidence regarding the effect of treatment on health-system costs remains limited. We evaluated the real-world clinical and economic outcomes of a transdiagnostic outpatient intervention, attention-based rehabilitation (ABR). Methods We conducted a pragmatic waitlist-controlled study in 54 consecutively referred patients with neurologist-diagnosed FND attending a specialist outpatient service. Clinical outcomes--including quality of life (Short Form-36), social and occupational participation (Work and Social Adjustment Scale), symptom severity, and mental health (Hospital Anxiety and Depression Scale)--were assessed at waitlist entry, treatment commencement, treatment completion, and 6 and 12 months post-treatment. Healthcare utilisation and costs were obtained prospectively from health-service financial records for the 6 months preceding treatment, the treatment period, and two consecutive 6-month post-treatment periods. Longitudinal clinical outcomes and healthcare costs were analysed using Bayesian mixed-effects and mixture models, respectively. Results All clinical measures remained stable or worsened during the waitlist control period. Across treatment, six of eight SF-36 domains, WSAS, employment status, and both HADS subdomains improved, with maintenance through 12 months. Patient-reported symptom improvement persisted post-treatment. Expected monthly health system costs approximately halved post-treatment, with net cost savings by approximately 50 days. Conclusion A fixed-duration, symptom-agnostic outpatient ABR programme was associated with durable improvements in functioning and quality of life, alongside substantial reductions in healthcare utilisation and cost, supporting scalable symptom-agnostic treatment models for FND.

Abstract Background Ketamine has emerged as an effective rapid-acting treatment for treatment-resistant depression (TRD), producing significant antidepressant effects within hours of administration. Given ketamine's capacity to induce states of heightened neuroplasticity and psychological openness, psychotherapy may represent a meaningful complement to its pharmacological effects - facilitating emotional processing, cognitive restructuring, and the consolidation of therapeutic gains. However, the adjunctive potential of structured psychotherapeutic support in ketamine-based interventions remains largely unexplored. Methods This preliminary, non-randomized, open-label clinical trial evaluated the adjunctive effects of ketamine-assisted psychotherapy (KAP) in an outpatient setting. Forty-six patients with TRD received eight weekly sessions of subcutaneous esketamine (0.5-1.0 mg/kg) and were allocated into two groups: esketamine without psychotherapeutic support (n = 23) and esketamine combined with structured KAP encompassing preparation, dosing accompaniment, and post-session integration (n = 23). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory-II (BDI-II) at multiple timepoints during treatment and at follow-up assessments up to six months after protocol completion. Results Both groups showed significant reductions in depressive symptoms throughout treatment. The KAP group demonstrated greater clinical improvement by the end of treatment, with between-group differences on the MADRS emerging at sessions 7 and 8. MADRS response and remission rates were 52.2% and 34.8% in the KET group, and 78.3% and 78.3% in the KAP group, respectively. BDI-II scores indicated earlier subjective improvement in the KAP group, with between-group differences emerging as early as the second session and persisting across multiple timepoints. No significant between-group differences were observed during the six-month follow-up, with both groups maintaining symptom reductions comparable to end-of-treatment levels. Conclusions These findings suggest that structured psychotherapeutic support may be associated with early clinical response and remission rates in subcutaneous esketamine treatment for TRD, potentially through facilitation of emotional processing, psychological flexibility, and behavioural change. Further controlled studies are needed to clarify the specific contribution of psychotherapy, investigate the mechanisms underlying this interaction, and optimize integrated treatment approaches for TRD. The trial was registered at https://ensaiosclinicos.gov.br/rg/RBR-1072m6nv . Keywords: esketamine; treatment-resistant depression; ketamine-assisted psychotherapy; innovative therapies.