Cost-Utility Analysis of Antipsychotic Reduction and Discontinuation in Patients with Long-term Schizophrenia and Psychosis in English Mental Health Trusts: The RADAR Study.

OBJECTIVES: The current recommended treatment for patients with recurrent episodes of schizophrenia and related conditions is antipsychotic medication. However, many antipsychotic users remain functionally impaired and experience serious physical and mental side effects. This study aims to assess the cost-effectiveness of a gradual antipsychotic reduction and discontinuation strategy compared to maintenance treatment over 24 months from a mental health services, health and social care, and societal perspectives. METHODS: Nineteen mental health trusts recruited patients to the RADAR randomised controlled trial. Quality adjusted life years (QALYs) were calculated from patient-reported EQ-5D-5L, with years of full capability (YFCs) calculated from the patient-reported ICECAP-A. Mental health services use and medication was collected from medical records. Other resource use and productivity loss was collected using self-completed questionnaires. Costs were calculated from published sources. RESULTS: 253 participants were randomised: 126 assigned to antipsychotic dose reduction and 127 to maintenance. There were no significant differences between arms in total costs for any perspectives. There were no significant difference in QALYs (-0.035; 95% CI: -0.123 to 0.052), whereas YFCs were significantly lower in the reduction arm compared to the maintenance arm (baseline-adjusted difference: -0.103; 95% CI: -0.192 to -0.014). The reduction strategy was dominated by maintenance for all analyses and was not likely to be cost-effective. CONCLUSIONS: It is unlikely that gradual antipsychotic reduction and discontinuation strategy is cost-effective compared with maintenance over two-years for patients with schizophrenia and other recurrent psychotic disorders who are on long-term antipsychotics.

Cognitive Behaviour Therapy for Depersonalisation Derealisation Disorder (CBT-f-DDD): Study protocol for a randomised controlled feasibility trial.

BACKGROUND: Depersonalisation-Derealisation Disorder (DDD) is a distressing mental health condition which causes individuals to have a sense of 'unreality' or detachment about themselves and/or the world around them. DDD is chronically under-researched, and as a result, under-diagnosed, with a population prevalence of about 1%. In systematic reviews, Cognitive Behavioural Therapy (CBT) has been found to be the only intervention with significant clinical impact on alleviating the symptoms of DDD. However, previous studies have suffered from small sample sizes, reliance on expert clinicians to provide therapy and narrow population demographics. This feasibility randomised controlled trial aims to provide more robust evidence for the treatment efficacy of CBT in DDD. METHODS: The study aims to recruit 40 participants from two NHS trusts, 20 per arm from two community Mental Health NHS services in London. The intervention group will receive 12-24 individual CBT sessions over a 6-month period from CBT therapists following specialist training for DDD. The control group will receive Treatment as Usual. We will assess the feasibility of a future RCT through measuring the acceptability of the intervention, and assessing our ability to recruit, retain and randomise participants. We will calculate the correlation of scores on the Cambridge Depersonalisation Scale, its baseline standard deviation, assess the magnitude/direction of change and characterise the uncertainty in the outcome scores and the probability that the results have been obtained by chance. DISCUSSION: The outputs of this trial will guide whether a definite RCT is feasible and acceptable, for both the clinician and participant. TRIAL REGISTRATION: The ISRCTN registration number is ISRCTN97686121(https://doi.org/10.1186/ISRCTN97686121).

External validation of a prognostic model to improve prediction of psychosis in primary care.

Background Early detection could reduce the duration of untreated psychosis. GPs are a vital part of the psychosis care pathway but find it difficult to detect the early features. An accurate risk prediction tool (P Risk) was developed to detect these. Aim The external validation of P Risk. Methods A retrospective cohort study using a validation dataset of 1,647,934 UK Clinical Practice Research Datalink primary care records linked to secondary care records. The same predictors (age, sex, ethnicity, social deprivation, consultations for suicidal behaviour, depression/anxiety and substance abuse, history of consultations for suicidal behaviour, smoking history and substance abuse and prescribed medications for depression/anxiety/PTSD/OCD and total number of consultations) were used as for P Risk development. Predictive risk, sensitivity, specificity, and likelihood ratios were calculated for various risk thresholds. Discrimination (Harrell's C) and calibration were calculated. Results were compared between the development (GOLD) and validation (AURUM) datasets. Findings Psychosis risk increased with values of the P Risk prognostic index. Incidence was highest in younger age groups and mainly higher in males. Harrell's C was 0.79 (95% CI 0.78, 0.79) in the validation dataset and 0.77 in the development dataset. A risk threshold of 1% gave sensitivity of 65.9% and specificity of 86.6%. Interpretation Further testing is required but P Risk has the potential to be used in primary care to detect future risk of psychosis.

Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Internet and Telephone Support for Discontinuing Long-Term Antidepressants: The REDUCE Cluster Randomized Trial.

Importance: There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. Objective: To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone. Design, Setting, and Participants: In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented. Interventions: Internet and telephone self-management support, codesigned and coproduced with patients and practitioners. Main Outcomes and Measures: The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis. Results: Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events. Conclusions and Relevance: In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue. Trial Registration: ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).

The association between sexual orientation and psychotic like experiences during adolescence: a prospective cohort study.

PURPOSE: Psychotic like experiences (PLEs) are relatively common during adolescence and associated with a range of negative outcomes. There is evidence that sexual minorities are at increased risk of mental health problems including depression, anxiety, self-harm and suicidality. However, no study has investigated the association between sexual orientation and psychotic experiences during adolescence. We compared trajectories of PLEs in sexual minority and heterosexual adolescents from 12 to 24 years of age. METHODS: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants provided data on sexual orientation at age 16 and PLEs at ages 12, 17 and 24. We used multi-level logistic regression models to test associations between sexual orientation and PLEs, before and after adjusting for covariates. We investigated whether the association differed according to time-point and sex using interaction terms. RESULTS: We found evidence that the odds of PLEs were 2.35 times (95% Confidence Interval 1.79-3.06, p < 0.0001) higher among sexual minority compared with heterosexual adolescents, across all ages, after adjusting for covariates. There was no evidence that the association between sexual orientation and PLEs differed according to time-point (p = 0.50) or sex (p = 0.29). CONCLUSION: We found an increased risk of psychosis in sexual minorities compared with heterosexuals, which was present from around 12 years of age and persisted until age 24. Early interventions to prevent this mental health inequality could include universal interventions to promote inclusivity and acceptance of diverse sexual orientations.

What predicts response to sertraline for people with depression in primary care? a secondary data analysis of moderators in the PANDA trial.

PURPOSE: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.

Adult-onset hearing loss and incident cognitive impairment and dementia - A systematic review and meta-analysis of cohort studies.

BACKGROUND: We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive. METHODS: We included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses. RESULTS: We identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 - 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 - 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 - 1.42]), and Alzheimer's disease dementia (ADD, HR=1.56 [95% CI = 1.30 - 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 - 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 - 1.27). The effect of hearing loss did not vary across potential moderators. CONCLUSIONS: Cohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD.

Identifying predictors of adverse outcomes after termination of seclusion in psychiatric intensive care units.

BACKGROUND: Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination. AIMS: To assess the factors that predict an adverse outcome within 24 h of seclusion termination. METHOD: In a cohort study of individuals secluded in psychiatric intensive care units, we investigated factors associated with any of the following outcomes: actual violence, attempted violence, or reinitiation of seclusion within 24 h of seclusion termination. Among the seclusion episodes that were initiated between 29 March 2018 and 4 March 2019, we investigated the exposures of medication cooperation, seclusion duration, termination out of working hours, involvement of medical staff in the final seclusion review, lack of insight, and agitation or irritability. In a mixed-effects logistic regression model, associations between each exposure and the outcome were calculated. Odds ratios were calculated unadjusted and adjusted for demographic and clinical variables. RESULTS: We identified 254 seclusion episodes from 122 individuals (40 female, 82 male), of which 106 (41.7%) had an adverse outcome within 24 h of seclusion termination. Agitation or irritability was associated with an adverse outcome, odds ratio 1.92 (95% CI 1.03 to 3.56, P = 0.04), but there was no statistically significant association with any of the other exposures, although confidence intervals were broad. CONCLUSIONS: Agitation or irritability in the hours preceding termination of seclusion may predict an adverse outcome. The study was not powered to detect other potentially clinically significant factors.

The association between academic achievement goals and adolescent depressive symptoms: a prospective cohort study in Australia.

BACKGROUND: Students define academic competence across two axes: developing skills and understanding (mastery) versus comparisons with peers (performance), and achieving goals (approach) versus avoiding failure (avoidance). We aimed to examine the longitudinal association between achievement goals and adolescent depressive symptoms. METHODS: We analysed data from the Kindergarten (recruited at age 4-5 years; born between March, 1999, and February, 2000; recruited from March, 2004 to November, 2004) and Baby (recruited at age 0-1 years; born between March, 2003, and February, 2004; recruited from March, 2004 to January, 2005) cohorts of the Longitudinal Study of Australian Children. Participants were identified through the Medicare enrolment database and sampled using a randomised selection stratified by postcode to represent the Australian population. Achievement goals were measured at age 12-13 years with the Achievement Goal Questionnaire (ranges from 1 to 7 on each of the four subscales), and depressive symptoms with the Short Mood and Feelings Questionnaire (score ranges from 0 to 26, with higher scores indicating more severe symptoms) at ages 14-15 years (both cohorts) and 16-17 years (Kindergarten cohort only). Analyses were linear multilevel and traditional regressions, with confounder adjustment, for participants with available data on the exposures, confounders, and outcome. FINDINGS: We included 3200 participants (1585 female and 1615 male) from the Kindergarten cohort and 2671 participants (1310 female and 1361 male) from the Baby cohort. A 1-point increase in mastery-approach goals was associated with decreased depressive symptom severity score (Kindergarten, -0·33 [95% CI -0·52 to -0·15]; Baby, -0·29 [-0·54 to -0·03]), while a 1-point increase in mastery-avoidance goals was associated with increased depressive symptom severity score (Kindergarten, 0·35 [95% CI 0·21 to 0·48]; Baby, 0·44 [0·25 to 0·64]). A 1-point increase in performance-avoidance goals was associated with increased depressive symptom severity score in the Kindergarten cohort but not the Baby cohort (Kindergarten, 0·26 [95% CI 0·11 to 0·41]; Baby, -0·04 [-0·27 to 0·19]). We found little evidence of an association between depressive symptom severity and performance-approach goals. INTERPRETATION: Depressive symptoms in adolescents were associated with their achievement goals, which could be targetable risk factors for future trials to investigate whether school-based interventions that aim to enhance factors consistent with mastery goals (ie, learning skills and understanding the subject, rather than assessing competence in comparison to peers) could prevent depression in adolescents. FUNDING: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society.

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

The role of depression and use of alcohol and other drugs after partner suicide in the association between suicide bereavement and suicide: cohort study in the Danish population.

BACKGROUND: Although suicide bereavement is associated with suicide and self-harm, evidence regarding mechanisms is lacking. We investigated whether depression and substance use (alcohol and/or other drugs) explain the association between partner suicide bereavement and suicide. METHODS: Linkage of nationwide, longitudinal data from Denmark for the period 1980-2016 facilitated a comparison of 22 668 individuals exposed to bereavement by a partner's suicide with 913 402 individuals bereaved by a partner's death due to other causes. Using causal mediation models, we estimated the degree to which depression and substance use (considered separately) mediated the association between suicide bereavement and suicide. RESULTS: Suicide-bereaved partners were found to have a higher risk of suicide (HRadj = 1.59, 95% CI 1.36-1.86) and of depression (ORadj 1.16, 95% CI 1.09-1.25) when compared to other-bereaved partners, but a lower risk of substance use (ORadj 0.83; 95% CI 0.78-0.88). An increased risk of suicide was found among any bereaved individuals with a depression diagnosis recorded post-bereavement (ORadj 3.92, 95% CI 3.55-4.34). Mediation analysis revealed that depression mediated 2% (1.68%; 95% CI 0.23%-3.14%; p = 0.024) of the association between suicide bereavement and suicide in partners when using bereaved controls. CONCLUSIONS: Depression is a partial mediator of the association between suicide bereavement and suicide. Efforts to prevent and optimize the treatment of depression in suicide-bereaved people could reduce their suicide risk. Our findings might be conservative because we did not include cases of depression diagnosed in primary care. Further work is needed to understand this and other mediators.

Patient-reported outcome measures for monitoring primary care patients with depression: the PROMDEP cluster RCT and economic evaluation.

Background: Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. Objective: To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure for monitoring depression, training practitioners in interpreting scores and giving patients feedback. Design: Parallel-group, cluster-randomised superiority trial; 1 : 1 allocation to intervention and control. Setting: UK primary care (141 group general practices in England and Wales). Inclusion criteria: Patients aged ≥ 18 years with a new episode of depressive disorder or symptoms, recruited mainly through medical record searches, plus opportunistically in consultations. Exclusions: Current depression treatment, dementia, psychosis, substance misuse and risk of suicide. Intervention: Administration of the Patient Health Questionnaire-9 questionnaire with patient feedback soon after diagnosis, and at follow-up 10-35 days later, compared with usual care. Primary outcome: Beck Depression Inventory, 2nd edition, symptom scores at 12 weeks. Secondary outcomes: Beck Depression Inventory, 2nd edition, scores at 26 weeks; antidepressant drug treatment and mental health service contacts; social functioning (Work and Social Adjustment Scale) and quality of life (EuroQol 5-Dimension, five-level) at 12 and 26 weeks; service use over 26 weeks to calculate NHS costs; patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale); and adverse events. Sample size: The original target sample of 676 patients recruited was reduced to 554 due to finding a significant correlation between baseline and follow-up values for the primary outcome measure. Randomisation: Remote computerised randomisation with minimisation by recruiting university, small/large practice and urban/rural location. Blinding: Blinding of participants was impossible given the open cluster design, but self-report outcome measures prevented observer bias. Analysis was blind to allocation. Analysis: Linear mixed models were used, adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering including practice as random effect. Quality of life and costs were analysed over 26 weeks. Qualitative interviews: Practitioner and patient interviews were conducted to reflect on trial processes and use of the Patient Health Questionnaire-9 using the Normalization Process Theory framework. Results: Three hundred and two patients were recruited in intervention arm practices and 227 patients were recruited in control practices. Primary outcome data were collected for 252 (83.4%) and 195 (85.9%), respectively. No significant difference in Beck Depression Inventory, 2nd edition, score was found at 12 weeks (adjusted mean difference -0.46, 95% confidence interval -2.16 to 1.26). Nor were significant differences found in Beck Depression Inventory, 2nd Edition, score at 26 weeks, social functioning, patient satisfaction or adverse events. EuroQol-5 Dimensions, five-level version, quality-of-life scores favoured the intervention arm at 26 weeks (adjusted mean difference 0.053, 95% confidence interval 0.013 to 0.093). However, quality-adjusted life-years over 26 weeks were not significantly greater (difference 0.0013, 95% confidence interval -0.0157 to 0.0182). Costs were lower in the intervention arm but, again, not significantly (-£163, 95% confidence interval -£349 to £28). Cost-effectiveness and cost-utility analyses, therefore, suggested that the intervention was dominant over usual care, but with considerable uncertainty around the point estimates. Patients valued using the Patient Health Questionnaire-9 to compare scores at baseline and follow-up, whereas practitioner views were more mixed, with some considering it too time-consuming. Conclusions: We found no evidence of improved depression management or outcome at 12 weeks from using the Patient Health Questionnaire-9, but patients' quality of life was better at 26 weeks, perhaps because feedback of Patient Health Questionnaire-9 scores increased their awareness of improvement in their depression and reduced their anxiety. Further research in primary care should evaluate patient-reported outcome measures including anxiety symptoms, administered remotely, with algorithms delivering clear recommendations for changes in treatment. Study registration: This study is registered as IRAS250225 and ISRCTN17299295. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 17. See the NIHR Funding and Awards website for further award information.

Depression is common, can be disabling and costs the nation billions. The National Health Service recommends general practitioners who treat people with depression use symptom questionnaires to help assess whether those people are getting better over time. A symptom questionnaire is one type of patient-reported outcome measure. Patient-reported outcome measures appear to benefit people having therapy and mental health care, but this approach has not been tested thoroughly in general practice. Most people with depression are treated in general practice, so it is important to test patient-reported outcome measures there, too. In this study, we tested whether using a patient-reported outcome measure helps people with depression get better more quickly. The study was a 'randomised controlled trial' in general practices, split into two groups. In one group, people with depression completed the Patient Health Questionnaire, or 'PHQ-9', patient-reported outcome measure, which measures nine symptoms of depression. In the other group, people with depression were treated as usual without the Patient Health Questionnaire-9. We fed the results of the Patient Health Questionnaire-9 back to the people with depression themselves to show them how severe their depression was and asked them to discuss the results with the practitioners looking after them. We found no differences between the patient-reported outcome measure group and the control group in their level of depression; their work or social life; their satisfaction with care from their practice; or their use of medicines, therapy or specialist care for depression. However, we did find that their quality of life was improved at 6 months, and the costs of the National Health Service services they used were lower. Using the Patient Health Questionnaire-9 can improve patients' quality of life, perhaps by making them more aware of improvement in their depression symptoms, and less anxious as a result. Future research should test using a patient-reported outcome measure that includes anxiety and processing the answers through a computer to give practitioners clearer advice on possible changes to treatment for depression.

Impact of physical and sexual abuse on risk of hospitalisations for physical and mental illnesses: insights from two large prospective cohort studies.

Background: Physical abuse can lead to severe health consequences that extend beyond immediate harm. We explored the associations of physical abuse experienced during childhood and adulthood with a wide range of adult health conditions requiring hospital treatment. Methods: We utilised data from a sub-cohort of 157,366 UK Biobank participants (46.4% of the baseline population; age range 45-81; 89,101 women) and repeated analyses in an independent population of 85,929 adults from the Finnish Public Sector (FPS) study (age range 17-78; 68,544 women). Participants in both cohorts reported instances of physical and sexual abuse at study baseline. Follow-up included 77 common health conditions ascertained from linkage data to national hospital and mortality registries. Findings: Mean follow-up duration was 4.6 years (SD 0.14) in UK Biobank and 10.6 years (4.3) in FPS. Physical and sexual abuse was associated with 22 mental and physical health conditions. After multivariable adjustments, participants who experienced abuse during both early and later stages of life had a 2.12- (95% confidence interval 1.39-3.23) to 3.37-fold (1.52-7.45) increased risk of mental and behavioural disorders, a 1.46 (1.20-1.79) to 1.83 (1.05-3.20) times increased risk of metabolic, haematologic, and respiratory diseases, and a 1.24 (1.07-1.45) times higher risk of inflammatory diseases compared with non-exposed participants. The absolute risk difference between these groups was greatest for metabolic and haematologic conditions (rate 381 and risk difference 160 per 100,000 person-years). Frailty, comorbidities, and competing risk of death did not modify these associations, but the possibility of bias or residual confounding cannot be excluded. Interpretation: Repeated exposure to physical and sexual abuse amplifies the risk of hospitalisations from mental disorders and physical diseases spanning diverse organ systems. Addressing this issue may necessitate multifaceted strategies, including shifts in societal norms, legal measures, and increased healthcare provision for affected individuals and their families. Funding: Wellcome Trust, UK Medical Research Council, U.S. National Institute on Aging, Academy of Finland.

Differences in psychological treatment outcomes by ethnicity and gender: an analysis of individual patient data.

PURPOSE: There are discrepancies in mental health treatment outcomes between ethnic groups, which may differ between genders. NHS Talking Therapies for anxiety and depression provide evidence-based psychological therapies for common mental disorders. This study examines the intersection between ethnicity and gender as factors associated with psychological treatment outcomes. Aims were to explore by gender: (1) differences in psychological treatment outcomes for minoritized ethnic people compared to White-British people, (2) whether differences are observed when controlling for clinical and socio-demographic factors associated with outcomes, and (3) whether organization-level factors moderate differences in outcomes between ethnic groups. METHODS: Patient data from eight NHS Talking Therapies for anxiety and depression services (n = 98,063) was used to explore associations between ethnicity and outcomes, using logistic regression. Stratified subsamples were used to separately explore factors associated with outcomes for males and females. RESULTS: In adjusted analyses, Asian (OR = 0.82 [95% CI 0.78; 0.87], p < .001, 'Other' (OR = 0.79 [95%CI 0.72-0.87], p < .001) and White-other (0.93 [95%CI 0.89-0.97], p < .001) ethnic groups were less likely to reliably recover than White-British people. Asian (OR = 1.48 [95% CI 1.35-1.62], p < .001), Mixed (OR = 1.18 [95% CI 1.05-1.34], p = .008), 'Other' (OR = 1.60 [95% CI 1.38-1.84], p < .001) and White-other (OR = 1.18 [95% CI 1.09-1.28], p < .001) groups were more likely to experience a reliable deterioration in symptoms. Poorer outcomes for these groups were consistent across genders. There was some evidence of interactions between ethnic groups and organization-level factors impacting outcomes, but findings were limited. CONCLUSIONS: Across genders, Asian, 'Other' and White-other groups experienced worse treatment outcomes across several measures in adjusted models. Reducing waiting times or offering more treatment sessions might lead to increased engagement and reduced drop-out for some patient groups.

Depression follow-up monitoring with the PHQ-9: an open cluster-randomised controlled trial.

BACKGROUND: Outcome monitoring of depression treatment is recommended but there is a lack of evidence on patient benefit in primary care. AIM: To test monitoring depression using the Patient Health Questionnaire (PHQ-9) with patient feedback. DESIGN AND SETTING: An open cluster-randomised controlled trial was undertaken in 141 group practices. METHOD: Adults with new depressive episodes were recruited through record searches and opportunistically. The exclusion criteria were as follows: dementia; psychosis; substance misuse; and suicide risk. The PHQ-9 was administered soon after diagnosis, and 10-35 days later. The primary outcome was the Beck Depression Inventory (BDI-II) score at 12 weeks. The secondary outcomes were as follows: BDI-II at 26 weeks; Work and Social Adjustment Scale (WSAS) and EuroQol EQ-5D-5L quality of life at 12 and 26 weeks; antidepressant treatment; mental health and social service contacts; adverse events, and Medical Interview Satisfaction Scale (MISS) over 26 weeks. RESULTS: In total, 302 patients were recruited to the intervention arm and 227 to the controls. At 12 weeks, 254 (84.1%) and 199 (87.7%) were followed-up, respectively. Only 40.9% of patients in the intervention had a GP follow-up PHQ-9 recorded. There was no significant difference in BDI-II score at 12 weeks (mean difference -0.46; 95% confidence interval [CI] = -2.16 to 1.26; adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering by practice). EQ-5D-5L quality-of-life scores were higher in the intervention arm at 26 weeks (adjusted mean difference 0.053; 95% CI = 0.013 to 0.093. A clinically significant difference in depression at 26 weeks could not be ruled out. No significant differences were found in social functioning, adverse events, or satisfaction. In a per-protocol analysis, antidepressant use and mental health contacts were significantly greater in patients in the intervention arm with a recorded follow-up PHQ-9 (P = 0.025 and P = 0.010, respectively). CONCLUSION: No evidence was found of improved depression outcome at 12 weeks from monitoring. The findings of possible benefits over 26 weeks warrant replication, investigating possible mechanisms, preferably with automated delivery of monitoring and more instructive feedback.

The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis.

Background: The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission. Methods: We searched MEDLINE, Embase, PsycINFO and AMED up to 13th November 2023 for longitudinal observational studies which measured disease outcomes in people with Parkinson's disease, with and without specific psychiatric comorbidities, and a minimum of two authors extracted summary data. Studies of individuals with other parkinsonian conditions and those with outcome measures that had high overlap with psychiatric symptoms were excluded to ensure face validity. For each exposure-outcome pair, a random-effects meta-analysis was conducted based on standardised mean difference, using adjusted effect sizes-where available-in preference to unadjusted effect sizes. Study quality was assessed using the Newcastle-Ottawa Scale. Between-study heterogeneity was assessed using the I2 statistic and publication bias was assessed using funnel plots. PROSPERO Study registration number: CRD42022373072. Findings: There were 55 eligible studies for inclusion in meta-analysis (n = 165,828). Data on participants' sex was available for 164,514, of whom 99,182 (60.3%) were male and 65,460 (39.7%) female. Study quality was mostly high (84%). Significant positive associations were found between psychosis and cognitive impairment (standardised mean difference [SMD] 0.44, [95% confidence interval [CI] 0.23-0.66], I2 30.9), psychosis and disease progression (SMD 0.46, [95% CI 0.12-0.80], I2 70.3%), depression and cognitive impairment (SMD 0.37 [95% CI 0.10-0.65], I2 27.1%), depression and disease progression (SMD 0.46 [95% CI 0.18-0.74], I2 52.2), depression and disability (SMD 0.42 [95% CI 0.25-0.60], I2 7.9%), and apathy and cognitive impairment (SMD 0.60 [95% CI 0.02-1.19], I2 27.9%). Between-study heterogeneity was moderately high. Interpretation: Psychosis, depression, and apathy in Parkinson's disease are all associated with at least one adverse outcome, including cognitive impairment, disease progression and disability. Whether this relationship is causal is not clear, but the mechanisms underlying these associations require exploration. Clinicians should consider these psychiatric comorbidities to be markers of a poorer prognosis in people with Parkinson's disease. Future studies should investigate the underlying mechanisms and which treatments for these comorbidities may affect Parkinson's disease outcomes. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at University College London Hospitals NHS Foundation Trust, National Brain Appeal.

Changes in Early Childhood Irritability and Its Association With Depressive Symptoms and Self-Harm During Adolescence in a Nationally Representative United Kingdom Birth Cohort.

OBJECTIVE: This study aimed to investigate longitudinal associations between changes in early childhood irritability, and depressive symptoms and self-harm at 14 years. METHOD: We used data from 7,225 children in a UK-based general population birth cohort. Childhood irritability was measured at 3, 5, and 7 years using 4 items from 2 questionnaires (the Children's Social Behaviour Questionnaire [CSBQ] and the Strengths and Difficulties Questionnaire [SDQ]). Participants reported depressive symptoms via the short Mood and Feelings Questionnaire (sMFQ) and self-harm via a single-item question, at 14 years. We used multilevel models to calculate within-child change in irritability between 3 and 7 years and examined associations between irritability, and depressive symptoms and self-harm at 14 years using linear and logistic regression models, respectively. We adjusted for child and family sociodemographic/economic characteristics, mental health difficulties, and child cognitive development. RESULTS: Irritability at ages 5 and 7 years was positively associated with depressive symptoms and self-harm at age 14 years. Irritability that remained high between 3 and 7 years was associated with depressive symptoms and self-harm at 14 years in unadjusted (depressive symptoms: ß coefficient = 0.22, 95 % CI = 0.08-0.37, p = .003; self-harm: odds ratio = 1.09, 95 % CI = 1.01-1.16, p = .019) and adjusted models (depressive symptoms: ß coefficient = 0.31, 95 % CI = 0.17-0.45, p < .001; self-harm: odds ratio = 1.12, 95 % CI = 1.0.4-1.19, p = .004). Results were similar in imputed samples. CONCLUSION: Children with irritability that remains high between 3 and 7 years are more likely to report higher depressive symptoms and self-harm during adolescence. These findings support early intervention for children with high irritability and universal interventions in managing irritability for parents of preschool-aged children.