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Background: Relapse of depression is common and contributes to the overall associated morbidity and burden. We lack evidence-based tools to estimate an individual's risk of relapse after treatment in primary care, which may help us more effectively target relapse prevention., Objective: The objective was to develop and validate a prognostic model to predict risk of relapse of depression in primary care., Methods: Multilevel logistic regression models were developed, using individual participant data from seven primary care-based studies (n=1244), to predict relapse of depression. The model was internally validated using bootstrapping, and generalisability was explored using internal-external cross-validation., Findings: Residual depressive symptoms (OR: 1.13 (95% CI: 1.07 to 1.20), p<0.001) and baseline depression severity (OR: 1.07 (1.04 to 1.11), p<0.001) were associated with relapse. The validated model had low discrimination (C-statistic 0.60 (0.55-0.65)) and miscalibration concerns (calibration slope 0.81 (0.31-1.31)). On secondary analysis, being in a relationship was associated with reduced risk of relapse (OR: 0.43 (0.28-0.67), p<0.001); this remained statistically significant after correction for multiple significance testing., Conclusions: We could not predict risk of depression relapse with sufficient accuracy in primary care data, using routinely recorded measures. Relationship status warrants further research to explore its role as a prognostic factor for relapse., Clinical Implications: Until we can accurately stratify patients according to risk of relapse, a universal approach to relapse prevention may be most beneficial, either during acute-phase treatment or post remission. Where possible, this could be guided by the presence or absence of known prognostic factors (eg, residual depressive symptoms) and targeted towards these., Trial Registration Number: NCT04666662., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Archer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists., Methods: A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a 'global rating of change' scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R)., Results: For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) -26.7 to -14.9) on the PHQ-9; 23% (95% CI -27.8 to -18.0) on the BDI-II and 26.8% (95% CI -33.5 to -20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were -1.7, -3.5 and -1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement., Conclusions: An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit., Funding: Funding. National Institute for Health Research.

Background: Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse., Objectives: Our objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication in well patients compared with maintenance, using patient-level trial data., Methods: We conducted a cost-utility analysis of 478 participants from 150 UK general practices recruited to a randomised, double-blind trial (ANTLER). QALYs were calculated from EQ-5D-5L and 12-Item Short Form survey (SF-12) results, with primary analysis using the EQ-5D-5L value set for England. Resource use was collected from primary care patient electronic medical records and self-completed questionnaires capturing mental-health-related resource use. Costs were calculated by applying standard UK unit costs to resource use. Adjustments were made for baseline variables., Results: Participants randomised to discontinuation had significantly worse utility scores at 3 months (- 0.032; 95% confidence interval [CI] - 0.053 to - 0.011) but no significant difference in QALYs (- 0.011; 95% CI - 0.026 to 0.003) or costs (£3.11; 95% CI - 41.28 to 47.50) at 12 months. The probability that discontinuation was cost effective compared with maintenance was 12.9% at a threshold of £20,000 per QALY gained., Conclusions: Discontinuation of antidepressants was unlikely to be cost effective compared with maintenance for currently well patients on long-term antidepressants. However, this analysis provides no information on the wider impact of antidepressants. Our findings provide information on the potential impact of discontinuing long-term maintenance antidepressants and facilitate improving guidance for shared patient-clinician decision making., Trial Registration: EudraCT number 2015-004210-26; ISRCTN number ISRCTN15969819., (© 2021. The Author(s).)

Objective: To investigate associations between major life events and prognosis independent of treatment type: (1) after adjusting for clinical prognostic factors and socio-demographics; (2) amongst patients with depressive episodes at least six-months long; and (3) patients with a first life-time depressive episode., Methods: Six RCTs of adults seeking treatment for depression in primary care met eligibility criteria, individual patient data (IPD) were collated from all six (n = 2858). Participants were randomized to any treatment and completed the same baseline assessment of life events, demographics and clinical prognostic factors. Two-stage random effects meta-analyses were conducted., Results: Reporting any major life events was associated with poorer prognosis regardless of treatment type. Controlling for baseline clinical factors, socio-demographics and social support resulted in minimal residual evidence of associations between life events and treatment prognosis. However, removing factors that might mediate the relationships between life events and outcomes reporting: arguments/disputes, problem debt, violent crime, losing one's job, and three or more life events were associated with considerably worse prognoses (percentage difference in 3-4 months depressive symptoms compared to no reported life events =30.3%(95%CI: 18.4-43.3))., Conclusions: Assessing for clinical prognostic factors, social support, and socio-demographics is likely to be more informative for prognosis than assessing self-reported recent major life events. However, clinicians might find it useful to ask about such events, and if they are still affecting the patient, consider interventions to tackle problems related to those events (e.g. employment support, mediation, or debt advice). Further investigations of the efficacy of such interventions will be important., (Copyright © 2021. Published by Elsevier B.V.)

Background: Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting., Methods: We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings., Results: A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group., Conclusions: Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)., (Copyright © 2021 Massachusetts Medical Society.)

Collaborative care in primary care has been shown to be effective for subthreshold depression in older adults in the 'CASPER' trial. However, to understand the impact of adherence, and to explore the minimum effective dose of collaborative care, we reanalysed the trial data using a complier average causal effect (CACE) analysis. Data were available for 705 participants, 519 with 12-month PHQ-9 scores. 'Compliance' could be observed for participants in the intervention group. Latent complier status in the control group was estimated. Completion of five or more sessions of care was defined as 'compliance'. Sensitivity analyses, using alternative cut-offs of two to eight sessions, assessed the impact of changing the definition of 'compliance'. Compliers in the intervention group had lower PHQ-9 scores at 12-month follow up than assumed compliers in the control group (1.75 lower, 95% confidence interval 0.29 to 3.21, p = 0.02), a greater effect than originally reported. Sensitivity analyses confirmed statistically significant differences between the intervention and control groups in those attending five or more sessions. We conclude that collaborative care is causally effective in reducing subthreshold depressive symptoms in older people who adhere to treatment. Our findings suggest the minimum effective dose is five sessions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: To evaluate the cost-effectiveness of a specialist smoking cessation package for people with severe mental illness DESIGN: Incremental cost-effectiveness analysis was undertaken from the UK National Health Service and Personal Social Services perspective over a 12-month time horizon. Total costs, including smoking cessation, health-care and social services costs and quality-adjusted life years (QALYs), derived from the five-level EuroQol 5-dimension (EQ-5D-5 L), collected from a randomized controlled trial, were used as outcome measures. The bootstrap technique was employed to assess the uncertainty., Setting: Sixteen primary care and 21 secondary care mental health sites in England., Participants: Adult smokers with bipolar affective disorder, schizoaffective disorder or schizophrenia and related illnesses (n = 526)., Intervention and Comparator: A bespoke smoking cessation (BSC) package for people with severe mental illness offered up to 12 individual sessions with a mental health smoking cessation practitioner versus usual care (UC). Of the participants who were randomized, 261 were in UC group and 265 were in BSC group., Measurements: BSC intervention cost was estimated from the treatment log. Costs of UC, health-care and social services and EQ-5D-5 L were collected at baseline, 6- and 12-month follow-ups. Incremental costs and incremental QLAYs were estimated using regression adjusting for respective baseline values and other baseline covariates., Findings: The mean total cost in the BSC group was £270 [95% confidence interval (CI) = -£1690 to £1424] lower than in the UC group, while the mean QALYs were 0.013 (95% CI = -0.008 to 0.045) higher, leading to BSC dominating UC (76% probability of cost-effective at £20 000/QALY)., Conclusions: A bespoke smoking cessation package for people with severe mental illness is likely to be cost-effective over 12 months compared with usual care provided by the UK's National Health Service and personal social services., (© 2020 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Around one in ten adults take antidepressants for depression in England, and their long-term use is increasing. Some need them to prevent relapse, but 30-50% could possibly stop them without relapsing and avoid adverse effects and complications of long-term use. However, stopping is not always easy due to withdrawal symptoms and a fear of relapse of depression. When general practitioners review patients on long-term antidepressants and recommend to those who are suitable to stop the medication, only 6-8% are able to stop. The Reviewing long-term antidepressant use by careful monitoring in everyday practice (REDUCE) research programme aims to identify safe and cost-effective ways of helping patients taking long-term antidepressants taper off treatment when appropriate., Methods: Design: REDUCE is a two-arm, 1:1 parallel group randomised controlled trial, with randomisation clustered by participating family practices., Setting: England and north Wales., Population: patients taking antidepressants for longer than 1 year for a first episode of depression or longer than 2 years for repeated episodes of depression who are no longer depressed and want to try to taper off their antidepressant use., Intervention: provision of 'ADvisor' internet programmes to general practitioners or nurse practitioners and to patients designed to support antidepressant withdrawal, plus three patient telephone calls from a psychological wellbeing practitioner. The control arm receives usual care. Blinding of patients, practitioners and researchers is not possible in an open pragmatic trial, but statistical and health economic data analysts will remain blind to allocation., Outcome Measures: the primary outcome is self-reported nine-item Patient Health Questionnaire at 6 months for depressive symptoms., Secondary Outcomes: depressive symptoms at other follow-up time points, anxiety, discontinuation of antidepressants, social functioning, wellbeing, enablement, quality of life, satisfaction, and use of health services for costs., Sample Size: 402 patients (201 intervention and 201 controls) from 134 general practices recruited over 15-18 months, and followed-up at 3, 6, 9 and 12 months. A qualitative process evaluation will be conducted through interviews with 15-20 patients and 15-20 practitioners in each arm to explore why the interventions were effective or not, depending on the results., Discussion: Helping patients reduce and stop antidepressants is often challenging for practitioners and time-consuming for very busy primary care practices. If REDUCE provides evidence showing that access to internet and telephone support enables more patients to stop treatment without increasing depression we will try to implement the intervention throughout the National Health Service, publishing practical guidance for professionals and advice for patients to follow, publicised through patient support groups., Trial Registration: ISRCTN:12417565. Registered on 7 October 2019.

Background: Relapse (the re-emergence of depression symptoms before full recovery) is common in depression and relapse prevention strategies are not well researched in primary care settings. Collaborative care is effective for treating acute phase depression but little is known about the use of relapse prevention strategies in collaborative care. We undertook a systematic review to identify and characterise relapse prevention strategies in the context of collaborative care., Methods: We searched for Randomised Controlled Trials (RCTs) of collaborative care for depression. In addition to published material, we obtained provider and patient manuals from authors to provide more detail on intervention content. We reported the extent to which collaborative care interventions addressed four relapse prevention components., Results: 93 RCTs were identified. 31 included a formal relapse prevention plan; 42 had proactive monitoring and follow-up after the acute phase; 39 reported strategies for optimising sustained medication adherence; and 20 of the trials reported psychological or psycho-educational treatments persisting beyond the acute phase or focussing on long-term health/relapse prevention. 30 (32.3%) did not report relapse prevention approaches., Limitations: We did not receive trial materials for approximately half of the trials, which limited our ability to identify relevant features of intervention content., Conclusion: Relapse is a significant risk amongst people treated for depression and interventions are needed that specifically address and minimise this risk. Given the advantages of collaborative care as a delivery system for depression care, there is scope for more consistency and increased effort to implement and evaluate relapse prevention strategies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier B.V.)

Background: Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response., Methods: The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants., Findings: Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication., Interpretation: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder., Funding: National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Digital or electronic mental health (e-mental health) interventions can be useful approaches in reducing the burden of depression, with tools available for use in prevention, treatment, or relapse prevention. They may have specific benefit for primary care, as depression is often managed in this setting. However, little is known about attitudes and barriers among GPs towards e-mental health interventions for depression., Aim: This study aimed to assess attitudes, knowledge, use, and barriers for depression-focused e-mental health among GPs across the UK., Design and Setting: An online survey of self-selecting GPs in the UK conducted over a 10-day period in December 2017., Method: The survey consisted of 13 multiple choice questions posted on the Doctors.net.uk (DNUK) website., Results: In all, 1044 responses were included; 72% of GPs reported using at least one type of e-mental health intervention for depression. Overall, GPs reported that e-mental health interventions are most effective when delivered in a guided way, rather than in an unguided manner. In addition, 92% of GPs reported that neither they nor their colleagues received e-mental health training., Conclusion: A moderate number of GPs use e-mental health for depression in their services, and report it is likely that its use will increase. There is a gap in training and awareness of effective interventions. GPs consider guided e-mental health interventions to be most effective, in contrast to the unguided way it is mostly offered in primary care., (© British Journal of General Practice 2019.)

Objective: To investigate whether two primary care activities that are framed as indicators of primary care quality (comprehensive care plans and annual reviews of physical health) influence unplanned utilisation of hospital services for people with serious mental illness (SMI)., Design, Setting, Participants: Retrospective observational cohort study using linked primary care and hospital records (Hospital Episode Statistics) for 5158 patients diagnosed with SMI between April 2006 and March 2014, who attended 213 primary care practices in England that contribute to the Clinical Practice Research Datalink GOLD database., Outcomes and Analysis: Cox survival models were used to estimate the associations between two primary care quality indicators (care plans and annual reviews of physical health) and the hazards of three types of unplanned hospital utilisation: presentation to accident and emergency departments (A&E), admission for SMI and admission for ambulatory care sensitive conditions (ACSC)., Results: Risk of A&E presentation was 13% lower (HR 0.87, 95% CI 0.77 to 0.98) and risk of admission to hospital for ACSC was 23% lower (HR 0.77, 95% CI 0.60 to 0.99) for patients with a care plan documented in the previous year compared with those without a care plan. Risk of A&E presentation was 19% lower for those who had a care plan documented earlier but not updated in the previous year (HR: 0.81, 95% CI 0.67 to 0.97) compared with those without a care plan. Risks of hospital admission for SMI were not associated with care plans, and none of the outcomes were associated with annual reviews., Conclusions: Care plans documented in primary care for people with SMI are associated with reduced risk of A&E attendance and reduced risk of unplanned admission to hospital for physical health problems, but not with risk of admission for mental health problems. Annual reviews of physical health are not associated with risk of unplanned hospital utilisation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: Serious mental illness (SMI) - which comprises long-term conditions such as schizophrenia, bipolar disorder, and other psychoses - has enormous costs for patients and society. In many countries, people with SMI are treated solely in primary care, and have particular needs for physical care., Aim: The objective of this study was to systematically review the literature to create a list of quality indicators relevant to patients with SMI that could be captured using routine data, and which could be used to monitor or incentivise better-quality primary care., Design and Setting: A systematic literature review, combined with a search of quality indicator databases and guidelines., Method: The authors assessed whether indicators could be measured from routine data and the quality of the evidence., Results: Out of 1847 papers and quality indicator databases identified, 27 were included, from which 59 quality indicators were identified, covering six domains. Of the 59 indicators, 52 could be assessed using routine data. The evidence base underpinning these indicators was relatively weak, and was primarily based on expert opinion rather than trial evidence., Conclusion: With appropriate adaptation for different contexts, and in line with the relative responsibilities of primary and secondary care, use of the quality indicators has the potential to improve care and to improve the physical and mental health of people with SMI. However, before the indicators can be used to monitor or incentivise primary care quality, more robust links need to be established, with improved patient outcomes., (© British Journal of General Practice 2017.)

Background: Efforts to reduce the burden of illness and personal suffering associated with depression in older adults have focused on those with more severe depressive syndromes. Less attention has been paid to those with mild disorders/subthreshold depression, but these patients also suffer significant impairments in their quality of life and level of functioning. There is currently no clear evidence-based guidance regarding treatment for this patient group., Objectives: To establish the clinical effectiveness and cost-effectiveness of a low-intensity intervention of collaborative care for primary care older adults who screened positive for subthreshold depression., Design: A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected., Setting: Thirty-two general practitioner (GP) practices in the north of England., Participants: A total of 705 participants aged ≥ 75 years during the pilot phase and ≥ 65 years during the main trial with subthreshold depression., Interventions: Participants in the intervention group received a low-intensity intervention of collaborative care, which included behavioural activation delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual GP care. Control-arm participants received only usual GP care., Main Outcome Measures: The primary outcome measure was a self-reported measure of depression severity, the Patient Health Questionnaire-9 items PHQ-9 score at 4 months post randomisation. Secondary outcome measures included the European Quality of Life-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder seven-item scale, Connor-Davidson Resilience Scale two-item version, a medication questionnaire and objective data. Participants were followed up for 12 months., Results: In total, 705 participants were randomised (collaborative care n  = 344, usual care n  = 361), with 586 participants (83%; collaborative care 76%, usual care 90%) followed up at 4 months and 519 participants (74%; collaborative care 68%, usual care 79%) followed up at 12 months. Attrition was markedly greater in the collaborative care arm. Model estimates at the primary end point of 4 months revealed a statistically significant effect in favour of collaborative care compared with usual care [mean difference 1.31 score points, 95% confidence interval (CI) 0.67 to 1.95 score points; p  < 0.001]. The difference equates to a standard effect size of 0.30, for which the trial was powered. Treatment differences measured by the PHQ-9 were maintained at 12 months' follow-up (mean difference 1.33 score points, 95% CI 0.55 to 2.10 score points; p  = 0.001). Base-case cost-effectiveness analysis found that the incremental cost-effectiveness ratio was £9633 per quality-adjusted life-year (QALY). On average, participants allocated to collaborative care displayed significantly higher QALYs than those allocated to the control group (annual difference in adjusted QALYs of 0.044, 95% bias-corrected CI 0.015 to 0.072; p  = 0.003)., Conclusions: Collaborative care has been shown to be clinically effective and cost-effective for older adults with subthreshold depression and to reduce the proportion of people who go on to develop case-level depression at 12 months. This intervention could feasibly be delivered in the NHS at an acceptable cost-benefit ratio. Important future work would include investigating the longer-term effect of collaborative care on the CASPER population, which could be conducted by introducing an extension to follow-up, and investigating the impact of collaborative care on managing multimorbidities in people with subthreshold depression., Trial Registration: Current Controlled Trials ISRCTN02202951., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 8. See the NIHR Journals Library website for further project information.

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers' mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women.

Background: There are limited data on detection disparities of common mental disorders in minority ethnic women., Aims: Describe the natural history of common mental disorders in primary care in the maternal period, characterise women with, and explore ethnic disparities in, detected and potentially missed common mental disorders., Method: Secondary analyses of linked birth cohort and primary care data involving 8991 (39.4% White British) women in Bradford. Common mental disorders were characterised through indications in the electronic medical record. Potentially missed common mental disorders were defined as an elevated General Health Questionnaire (GHQ-28) score during pregnancy with no corresponding common mental disorder markers in the medical record., Results: Estimated prevalence of pre-birth common mental disorders was 9.5%, rising to 14.0% 3 years postnatally. Up to half of cases were potentially missed. Compared with White British women, minority ethnic women were twice as likely to have potentially missed common mental disorders and half as likely to have a marker of screening for common mental disorders., Conclusions: Common mental disorder detection disparities exist for minority ethnic women in the maternal period., (© The Royal College of Psychiatrists 2016.)

Background: People with depression are usually managed in primary care and antidepressants are often the first-line treatment, but only one third of patients respond fully to a single antidepressant. This paper describes the protocol for a randomised controlled trial (MIR) to investigate the extent to which the addition of the antidepressant mirtazapine is effective in reducing the symptoms of depression compared with placebo in patients who are still depressed after they have been treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) for at least 6 weeks in primary care., Methods/design: MIR is a two-parallel group, multi-centre, pragmatic, placebo controlled, randomised trial with allocation at the level of the individual. Eligible participants are those who: are aged 18 years or older; are currently taking an SSRI/SNRI antidepressant (for at least 6 weeks at an adequate dose); score ≥ 14 on the Beck Depression Inventory (BDI-II); have adhered to their medication; and meet ICD-10 criteria for depression (assessed using the Clinical Interview Schedule-Revised version). Participants who give written, informed consent, will be randomised to receive either oral mirtazapine or matched placebo, starting at 15 mg daily for 2 weeks and increasing to 30 mg daily thereafter, for up to 12 months (to be taken in addition to their usual antidepressant). Participants, their GPs, and the research team will all be blind to the allocation. The primary outcome will be depression symptoms at 12 weeks post randomisation, measured as a continuous variable using the BDI-II. Secondary outcomes (measured at 12, 24 and 52 weeks) include: response (reduction in depressive symptoms (BDI-II score) of at least 50% compared to baseline); remission of depression symptoms (BDI-II <10); change in anxiety symptoms; adverse effects; quality of life; adherence to antidepressant medication; health and social care use, time off work and cost-effectiveness. All outcomes will be analysed on an intention-to-treat basis. A qualitative study will explore patients' views and experiences of either taking two antidepressants, or an antidepressant and a placebo; and GPs' views on prescribing a second antidepressant in this patient group., Discussion: The MIR trial will provide evidence on the clinical and cost-effectiveness of mirtazapine as an adjunct to SSRI/SNRI antidepressants for patients in primary care who have not responded to monotherapy., Trial Registration: EudraCT Number: 2012-000090-23 (Registered January 2012); ISRCTN06653773 (Registered September 2012).

Background: Self-administered questionnaires, such as the Patient Health Questionnaire (PHQ-9), are regularly used in clinical practice to guide prescribing or to measure recovery and response to treatment. There are concerns that patients are not all interpreting the questionnaire items in the same way. Cognitive interviewing is a research technique that identifies 'interpretative measurement error' (IME). IME is distinct from traditional components of measurement error, such as not reading the question as worded, or recording answers inaccurately., Aim: To use cognitive interviewing techniques to explore patterns in answer mapping and comprehension of the PHQ-9 questionnaire to ascertain whether the measure captures meaningful symptoms of low mood., Design and Setting: Qualitative study using cognitive interviewing techniques and card sorting in six GP practices in Bristol., Method: The study recruited 18 participants at the point of entry to a longitudinal primary care depression cohort study, PANDA (the indications for Prescribing ANtiDepressants that will leAd to a clinical benefit). Participants were interviewed 2, 4, and 6 weeks after their baseline visit. Cognitive interviews were digitally recorded. Analysis used the digital audio file, rather than verbatim transcripts, as it retained important features needed for analyses., Results: Cognitive interviewing revealed that items on the PHQ-9 are interpreted in a range of ways, that patients often cannot 'fit' their experience into the response options, and therefore often feel the questionnaire is misrepresenting their experience of meaningful symptoms of low mood., Conclusion: The PHQ-9 may be missing the presence and/or intensity of certain symptoms that are meaningful to patients. Clinicians should adopt caution when using it., (© British Journal of General Practice 2016.)

Background: Collaborative care is effective for depression management in the USA. There is little UK evidence on its clinical effectiveness and cost-effectiveness., Objective: To determine the clinical effectiveness and cost-effectiveness of collaborative care compared with usual care in the management of patients with moderate to severe depression., Design: Cluster randomised controlled trial., Setting: UK primary care practices (n = 51) in three UK primary care districts., Participants: A total of 581 adults aged ≥ 18 years in general practice with a current International Classification of Diseases, Tenth Edition depressive episode, excluding acutely suicidal people, those with psychosis, bipolar disorder or low mood associated with bereavement, those whose primary presentation was substance abuse and those receiving psychological treatment., Interventions: Collaborative care: 14 weeks of 6-12 telephone contacts by care managers; mental health specialist supervision, including depression education, medication management, behavioural activation, relapse prevention and primary care liaison. Usual care was general practitioner standard practice., Main Outcome Measures: Blinded researchers collected depression [Patient Health Questionnaire-9 (PHQ-9)], anxiety (General Anxiety Disorder-7) and quality of life (European Quality of Life-5 Dimensions three-level version), Short Form questionnaire-36 items) outcomes at 4, 12 and 36 months, satisfaction (Client Satisfaction Questionnaire-8) outcomes at 4 months and treatment and service use costs at 12 months., Results: In total, 276 and 305 participants were randomised to collaborative care and usual care respectively. Collaborative care participants had a mean depression score that was 1.33 PHQ-9 points lower [n = 230; 95% confidence interval (CI) 0.35 to 2.31; p = 0.009] than that of participants in usual care at 4 months and 1.36 PHQ-9 points lower (n = 275; 95% CI 0.07 to 2.64; p = 0.04) at 12 months after adjustment for baseline depression (effect size 0.28, 95% CI 0.01 to 0.52; odds ratio for recovery 1.88, 95% CI 1.28 to 2.75; number needed to treat 6.5). Quality of mental health but not physical health was significantly better for collaborative care at 4 months but not at 12 months. There was no difference for anxiety. Participants receiving collaborative care were significantly more satisfied with treatment. Differences between groups had disappeared at 36 months. Collaborative care had a mean cost of £272.50 per participant with similar health and social care service use between collaborative care and usual care. Collaborative care offered a mean incremental gain of 0.02 (95% CI -0.02 to 0.06) quality-adjusted life-years (QALYs) over 12 months at a mean incremental cost of £270.72 (95% CI -£202.98 to £886.04) and had an estimated mean cost per QALY of £14,248, which is below current UK willingness-to-pay thresholds. Sensitivity analyses including informal care costs indicated that collaborative care is expected to be less costly and more effective. The amount of participant behavioural activation was the only effect mediator., Conclusions: Collaborative care improves depression up to 12 months after initiation of the intervention, is preferred by patients over usual care, offers health gains at a relatively low cost, is cost-effective compared with usual care and is mediated by patient activation. Supervision was by expert clinicians and of short duration and more intensive therapy may have improved outcomes. In addition, one participant requiring inpatient treatment incurred very significant costs and substantially inflated our cost per QALY estimate. Future work should test enhanced intervention content not collaborative care per se., Trial Registration: Current Controlled Trials ISRCTN32829227., Funding: This project was funded by the Medical Research Council (MRC) (G0701013) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.

Background: Computerised cognitive behaviour therapy (cCBT) has been developed as an efficient form of therapy delivery with the potential to enhance access to psychological care. Independent research is needed which examines both the clinical effectiveness and cost-effectiveness of cCBT over the short and longer term., Objectives: To compare the clinical effectiveness and cost-effectiveness of cCBT as an adjunct to usual general practitioner (GP) care against usual GP care alone, for a free-to-use cCBT program (MoodGYM; National Institute for Mental Health Research, Australian National University, Canberra, Australia) and a commercial pay-to-use cCBT program (Beating the Blues(®); Ultrasis, London, UK) for adults with depression, and to determine the acceptability of cCBT and the experiences of users., Design: A pragmatic, multicentre, three-armed, parallel, randomised controlled trial (RCT) with concurrent economic and qualitative evaluations. Simple randomisation was used. Participants and researchers were not blind to treatment allocation., Setting: Primary care in England., Participants: Adults with depression who scored ≥ 10 on the Patient Health Questionnaire-9 (PHQ-9)., Interventions: Participants who were randomised to either of the two intervention groups received cCBT (Beating the Blues or MoodGYM) in addition to usual GP care. Participants who were randomised to the control group were offered usual GP care., Main Outcome Measures: The primary outcome was depression at 4 months (PHQ-9). Secondary outcomes were depression at 12 and 24 months; measures of mental health and health-related quality of life at 4, 12 and 24 months; treatment preference; and the acceptability of cCBT and experiences of users., Results: Clinical effectiveness: 210 patients were randomised to Beating the Blues, 242 patients were randomised to MoodGYM and 239 patients were randomised to usual GP care (total 691). There was no difference in the primary outcome (depression measured at 4 months) either between Beating the Blues and usual GP care [odds ratio (OR) 1.19, 95% confidence interval (CI) 0.75 to 1.88] or between MoodGYM and usual GP care (OR 0.98, 95% CI 0.62 to 1.56). There was no overall difference across all time points for either intervention compared with usual GP care in a mixed model (Beating the Blues versus usual GP care, p = 0.96; and MoodGYM versus usual GP care, p = 0.11). However, a small but statistically significant difference between MoodGYM and usual GP care at 12 months was found (OR 0.56, 95% CI 0.34 to 0.93). Free-to-use cCBT (MoodGYM) was not inferior to pay-to-use cCBT (Beating the Blues) (OR 0.91, 90% CI 0.62 to 1.34; p = 0.69). There were no consistent benefits of either intervention when secondary outcomes were examined. There were no serious adverse events thought likely to be related to the trial intervention. Despite the provision of regular technical telephone support, there was low uptake of the cCBT programs. Cost-effectiveness: cost-effectiveness analyses suggest that neither Beating the Blues nor MoodGYM appeared cost-effective compared with usual GP care alone. Qualitative evaluation: participants were often demotivated to access the computer programs, by reason of depression. Some expressed the view that a greater level of therapeutic input would be needed to promote engagement., Conclusions: The benefits that have previously been observed in developer-led trials were not found in this large pragmatic RCT. The benefits of cCBT when added to routine primary care were minimal, and uptake of this mode of therapy was relatively low. There remains a clinical and economic need for effective low-intensity psychological treatments for depression with improved patient engagement., Trial Registration: This trial is registered as ISRCTN91947481., Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme.

Study Question: How effective is supported computerised cognitive behaviour therapy (cCBT) as an adjunct to usual primary care for adults with depression?, Methods: This was a pragmatic, multicentre, three arm, parallel randomised controlled trial with simple randomisation. Treatment allocation was not blinded. Participants were adults with symptoms of depression (score ≥ 10 on nine item patient health questionnaire, PHQ-9) who were randomised to receive a commercially produced cCBT programme ("Beating the Blues") or a free to use cCBT programme (MoodGYM) in addition to usual GP care. Participants were supported and encouraged to complete the programme via weekly telephone calls. Control participants were offered usual GP care, with no constraints on the range of treatments that could be accessed. The primary outcome was severity of depression assessed with the PHQ-9 at four months. Secondary outcomes included health related quality of life (measured by SF-36) and psychological wellbeing (measured by CORE-OM) at four, 12, and 24 months and depression at 12 and 24 months., Study Answer and Limitations: Participants offered commercial or free to use cCBT experienced no additional improvement in depression compared with usual GP care at four months (odds ratio 1.19 (95% confidence interval 0.75 to 1.88) for Beating the Blues v usual GP care; 0.98 (0.62 to 1.56) for MoodGYM v usual GP care). There was no evidence of an overall difference between either programme compared with usual GP care (0.99 (0.57 to 1.70) and 0.68 (0.42 to 1.10), respectively) at any time point. Commercially provided cCBT conferred no additional benefit over free to use cCBT or usual GP care at any follow-up point. Uptake and use of cCBT was low, despite regular telephone support. Nearly a quarter of participants (24%) had dropped out by four months. The study did not have enough power to detect small differences so these cannot be ruled out. Findings cannot be generalised to cCBT offered with a much higher level of guidance and support., What This Study Adds: Supported cCBT does not substantially improve depression outcomes compared with usual GP care alone. In this study, neither a commercially available nor free to use computerised CBT intervention was superior to usual GP care., Funding, Competing Interests, Data Sharing: Commissioned and funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project No 06/43/05). The authors have no competing interests. Requests for patient level data will be considered by the REEACT trial management groupTrial registration Current Controlled Trials ISRCTN91947481., (© Gilbody et al 2015.)

Background: The prevalence of depressive symptoms in older people may be as high as 20 %. Depression in older people is associated with loss, loneliness and physical co-morbidities; it is known to be under-diagnosed and under-treated. Older people may find it difficult to speak to their GPs about low mood, and GPs may avoid identifying depression due to limited consultation time and referral options for older patients., Methods: A nested qualitative study in a randomised controlled trial for older people with moderate to severe depression: the CASPER Plus Trial (Collaborative Care for Screen Positive Elders). We interviewed GPs, case managers (CM) and patient participants to explore perspectives and experiences of delivering and receiving a psychosocial intervention, developed specifically for older adults in primary care, within a collaborative care framework. Transcripts were analysed thematically using principles of constant comparison., Results: Thirty three interviews were conducted and, across the three data-sets, four main themes were identified: revealing hidden depression, reducing the 'blind spots', opportunity to talk outside the primary care consultation and 'moving on' from depression., Conclusions: Depression in older people is commonly hidden, and may coexist with physical conditions that are prioritised by both patients and GPs. Being invited to participate in a trial about depression may allow older people to disclose their feelings, name the problem, and seek help. Offering older people an opportunity to talk outside the primary care consultation is valued by patients and GPs. A psychosocial intervention delivered by a case manager in the primary care setting may fill the gap in the care of older people with depression., Trial Registration: Current Controlled Trials ISRCTN45842879 .

Purpose of Research: To validate the Whooley questions as a screening tool for depression amongst a population of older adults in UK primary care., Objective: To assess the diagnostic performance of the Whooley questions as a screening tool for depression amongst older adults in UK primary care., Participants: A cross-sectional validation study was conducted with 766 patients aged ≥75 from UK primary care, recruited via 17 general practices based in the North of England during the pilot phase of a randomized controlled trial., Main Outcome Measures: Sensitivity, specificity and likelihood ratios comparing the index test (two Whooley questions) with a diagnosis of major depressive disorder (MDD) ascertained by the reference standard Mini International Neuropsychiatric Interview (MINI)., Results: The two screening questions had a sensitivity of 94.3% (95% confidence interval, 80.8-99.3%) and specificity of 62.7% (95% confidence interval, 59.0-66.2%). The likelihood ratio for a positive test was 2.5 (95% confidence interval, 2.2-2.9) and the likelihood ratio for a negative test was 0.09 (95% confidence interval, 0.02-0.35)., Conclusion: The two Whooley questions missed few cases of depression. However, they were responsible for a high rate of false positives. This creates additional burden on general practitioners, to conduct more detailed investigation on patients who screen positive, but many of whom turn out not to have MDD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Depression accounts for the greatest disease burden of all mental health disorders, contributes heavily to healthcare costs, and by 2020 is set to become the second largest cause of global disability. Although 10% to 16% of people aged 65 years and over are likely to experience depressive symptoms, the condition is under-diagnosed and often inadequately treated in primary care. Later-life depression is associated with chronic illness and disability, cognitive impairment and social isolation. With a progressively ageing population it becomes increasingly important to refine strategies to identity and manage depression in older people. Currently, management may be limited to the prescription of antidepressants where there may be poor concordance; older people may lack awareness of psychosocial interventions and general practitioners may neglect to offer this treatment option., Methods/design: CASPER Plus is a multi-centre, randomised controlled trial of a collaborative care intervention for individuals aged 65 years and over experiencing moderate to severe depression. Selected practices in the North of England identify potentially eligible patients and invite them to participate in the study. A diagnostic interview is carried out and participants with major depressive disorder are randomised to either collaborative care or usual care. The recruitment target is 450 participants. The intervention, behavioural activation and medication management in a collaborative care framework, has been adapted to meet the complex needs of older people. It is delivered over eight to 10 weekly sessions by a case manager liaising with general practitioners. The trial aims to evaluate the clinical and cost effectiveness of collaborative care in addition to usual GP care versus usual GP care alone. The primary clinical outcome, depression severity, will be measured with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 4, 12 and 18 months. Cost effectiveness analysis will assess health-related quality of life using the SF-12 and EQ-5D and will examine cost-consequences of collaborative care. A qualitative process evaluation will be undertaken to explore acceptability, gauge the extent to which the intervention is implemented and to explore sustainability beyond the clinical trial., Discussion: Results will add to existing evidence and a positive outcome may lead to the commissioning of this model of service in primary care., Trial Registration: ISRCTN45842879 (24 July 2012).

Background: Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking., Aims: To assess the cost-effectiveness of collaborative care in a UK primary care setting., Methods: An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane., Results: The collaborative care intervention had a mean cost of £272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: -0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of £270.72 (95% CI: -202.98, 886.04), and resulted in an estimated mean cost per QALY of £14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual., Conclusion: Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting.

Objective: To compare the clinical effectiveness of collaborative care with usual care in the management of patients with moderate to severe depression., Design: Cluster randomised controlled trial., Setting: 51 primary care practices in three primary care districts in the United Kingdom., Participants: 581 adults aged 18 years and older who met ICD-10 (international classification of diseases, 10th revision) criteria for a depressive episode on the revised Clinical Interview Schedule. We excluded acutely suicidal patients and those with psychosis, or with type I or type II bipolar disorder; patients whose low mood was associated with bereavement or whose primary presenting problem was alcohol or drug abuse; and patients receiving psychological treatment for their depression by specialist mental health services. We identified potentially eligible participants by searching computerised case records in general practices for patients with depression., Interventions: Collaborative care, including depression education, drug management, behavioural activation, relapse prevention, and primary care liaison, was delivered by care managers. Collaborative care involved six to 12 contacts with participants over 14 weeks, supervised by mental health specialists. Usual care was family doctors' standard clinical practice., Main Outcome Measures: Depression symptoms (patient health questionnaire 9; PHQ-9), anxiety (generalised anxiety disorder 7; GAD-7), and quality of life (short form 36 questionnaire; SF-36) at four and 12 months; satisfaction with service quality (client satisfaction questionnaire; CSQ-8) at four months., Results: 276 participants were allocated to collaborative care and 305 allocated to usual care. At four months, mean depression score was 11.1 (standard deviation 7.3) for the collaborative care group and 12.7 (6.8) for the usual care group. After adjustment for baseline depression, mean depression score was 1.33 PHQ-9 points lower (95% confidence interval 0.35 to 2.31, P=0.009) in participants receiving collaborative care than in those receiving usual care at four months, and 1.36 points lower (0.07 to 2.64, P=0.04) at 12 months. Quality of mental health but not physical health was significantly better for collaborative care than for usual care at four months, but not 12 months. Anxiety did not differ between groups. Participants receiving collaborative care were significantly more satisfied with treatment than those receiving usual care. The number needed to treat for one patient to drop below the accepted diagnostic threshold for depression on the PHQ-9 was 8.4 immediately after treatment, and 6.5 at 12 months., Conclusions: Collaborative care has persistent positive effects up to 12 months after initiation of the intervention and is preferred by patients over usual care., Trial Registration Number: ISRCTN32829227.

Background: In the United Kingdom, clinical guidelines recommend that services for depression and anxiety should be structured around a stepped care model, where patients receive treatment at different 'steps,' with the intensity of treatment (i.e., the amount and type) increasing at each step if they fail to benefit at previous steps. There are very limited data available on the implementation of this model, particularly on the intensity of psychological treatment at each step. Our objective was to describe patient pathways through stepped care services and the impact of this on patient flow and management., Methods: We recorded service design features of four National Health Service sites implementing stepped care (e.g., the types of treatments available and their links with other treatments), together with the actual treatments received by individual patients and their transitions between different treatment steps. We computed the proportions of patients accessing, receiving, and transiting between the various steps and mapped these proportions visually to illustrate patient movement., Results: We collected throughput data on 7,698 patients referred. Patient pathways were highly complex and very variable within and between sites. The ratio of low (e.g., self-help) to high-intensity (e.g., cognitive behaviour therapy) treatments delivered varied between sites from 22:1, through 2.1:1, 1.4:1 to 0.5:1. The numbers of patients allocated directly to high-intensity treatment varied from 3% to 45%. Rates of stepping up from low-intensity treatment to high-intensity treatment were less than 10%., Conclusions: When services attempt to implement the recommendation for stepped care in the National Institute for Health and Clinical Excellence guidelines, there were significant differences in implementation and consequent high levels of variation in patient pathways. Evaluations driven by the principles of implementation science (such as targeted planning, defined implementation strategies, and clear activity specification around service organisation) are required to improve evidence on the most effective, efficient, and acceptable stepped care systems.

Background: Although the PHQ-9 is widely used in primary care, little is known about its performance in quantifying improvement. The original validation study of the PHQ-9 defined clinically significant change as a post-treatment score of ≤9 combined with improvement of 50%, but it is unclear how this relates to other theoretically informed methods of defining successful outcome. We compared a range of definitions of clinically significant change (original definition, asymptomatic criterion, reliable and clinically significant change criteria a, b and c) in a clinical trial of a community-level depression intervention., Method: Randomised Control Trial of collaborative care for depression. Levels of agreement were calculated between the standard definition, other definitions, and gold-standard diagnostic interview., Results: The standard definition showed good agreement (kappa>0.60) with the other definitions and had moderate, though acceptable, agreement with the diagnostic interview (kappa=0.58). The standard definition corresponded closely to reliable and clinically significant change criterion c, the recommended method of quantifying improvement when clinical and non-clinical distributions overlap., Limitations: The absence of follow-up data meant that an asymptomatic criterion rather than remission or recovery criteria were used., Conclusion: The close agreement between the standard definition and reliable and clinically significant change criterion c provides some support for the standard definition of improvement. However, it may be preferable to use a reliable change index rather than 50% improvement. Remission status, based on the asymptomatic range and a lower PHQ-9 score, may provide a useful additional category of clinical change., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: To evaluate the cost effectiveness of routine screening for postnatal depression in primary care., Design: Cost effectiveness analysis with a decision model of alternative methods of screening for depression, including standardised postnatal depression and generic depression instruments. The performance of screening instruments was derived from a systematic review and bivariate meta-analysis at a range of instrument cut points; estimates of other relevant parameters were derived from literature sources and relevant databases. A decision tree considered the full treatment pathway from the possible onset of postnatal depression through identification, treatment, and possible relapse., Setting: Primary care., Participants: A hypothetical population of women assessed for postnatal depression either via routine care only or supplemented by use of formal identification methods six weeks postnatally, as recommended in recent guidelines., Main Outcome Measures: Costs expressed in 2006-7 prices and impact on health outcomes expressed in terms of quality adjusted life years (QALYs). The time horizon of the analysis was one year., Results: The routine application of either postnatal or general depression questionnaires did not seem to be cost effective compared with routine care only. The Edinburgh postnatal depression scale (at a cut point of 16) had an incremental cost effectiveness ratio (ICER) of pound 41,103 (euro 45,398, $67,130) per QALY compared with routine care only. The ICER for all other strategies ranged from pound 49,928 to pound 272,463 per QALY versus routine care only, while the probability that no formal identification strategy was cost effective was 88% (59%) at a cost effectiveness threshold of pound 20,000 ( pound 30,000) per QALY. While sensitivity analysis indicated that the cost of managing incorrectly identified depression (false positive result) was an important driver of the model, formal identification approaches did not seem to be cost effective at any feasible estimate of this cost., Conclusions: Formal identification methods for postnatal depression do not seem to represent value for money for the NHS. The major determinant of cost effectiveness seems to be the potential additional costs of managing women incorrectly diagnosed as depressed. Formal identification methods for postnatal depression do not currently satisfy the National Screening Committee's criteria for the adoption of a screening strategy as part of national health policy.

Background: Comprising of both organisational and patient level components, collaborative care is a potentially powerful intervention for improving depression treatment in UK primary Care. However, as previous models have been developed and evaluated in the United States, it is necessary to establish the effect of collaborative care in the UK in order to determine whether this innovative treatment model can replicate benefits for patients outside the US. This Phase III trial was preceded by a Phase II patient level RCT, following the MRC Complex Intervention Framework., Methods/design: A multi-centre controlled trial with cluster-randomised allocation of GP practices. GP practices will be randomised to usual care control or to "collaborative care" - a combination of case manager coordinated support and brief psychological treatment, enhanced specialist and GP communication. The primary outcome will be symptoms of depression as assessed by the PHQ-9., Discussion: If collaborative care is demonstrated to be effective we will have evidence to enable the NHS to substantially improve the organisation of depressed patients in primary care, and to assist primary care providers to deliver a model of enhanced depression care which is both effective and acceptable to patients.

Background: The management of depression in primary care is a significant issue for health services worldwide. "Collaborative care" interventions are effective, but little is known about which aspects of these complex interventions are essential., Aims: To use meta-regression to identify "active ingredients" in collaborative care models for depression in primary care., Method: Studies were identified using systematic searches of electronic databases. The content of collaborative care interventions was coded, together with outcome data on antidepressant use and depressive symptoms. Meta-regression was used to examine relationships between intervention content and outcomes., Results: There was no significant predictor of the effect of collaborative care on antidepressant use. Key predictors of depressive symptom outcomes included systematic identification of patients, professional background of staff and specialist supervision., Conclusions: Meta-regression may be useful in examining "active ingredients" in complex interventions in mental health.

Background: Depression is common in primary care but is suboptimally managed. Collaborative care, that is, structured care involving a greater role of nonmedical specialists to augment primary care, has emerged as a potentially effective candidate intervention to improve quality of primary care and patient outcomes., Methods: To quantify the short-term and longer-term effectiveness of collaborative care compared with standard care and to understand mechanisms of action by exploring between-study heterogeneity, we conducted a systematic review of randomized controlled trials that compared collaborative care with usual primary care in patients with depression. We searched MEDLINE (from the beginning of 1966), EMBASE (from the beginning of 1980), CINAHL (from the beginning of 1980), PsycINFO (from the beginning of 1980), the Cochrane Library (from the beginning of 1966), and DARE (Database of Abstracts of Reviews of Effectiveness) (from the beginning of 1985) databases from study inception to February 6, 2006., Results: We found 37 randomized studies including 12 355 patients with depression receiving primary care. Random effects meta-analysis showed that depression outcomes were improved at 6 months (standardized mean difference, 0.25; 95% confidence interval, 0.18-0.32), and evidence of longer-term benefit was found for up to 5 years (standardized mean difference, 0.15; 95% confidence interval, 0.001-0.31). When exploring determinants of effectiveness, effect size was directly related to medication compliance and to the professional background and method of supervision of case managers. The addition of brief psychotherapy did not substantially improve outcome, nor did increased numbers of sessions. Cumulative meta-analysis showed that sufficient evidence had emerged by 2000 to demonstrate the statistically significant benefit of collaborative care., Conclusions: Collaborative care is more effective than standard care in improving depression outcomes in the short and longer terms. Future research needs to address the implementation of collaborative care, particularly in settings other than the United States.

Background: A number of enhancement strategies have been proposed to improve the quality and outcome of care for depression in primary care settings. Decision-makers are likely to need to know whether these interventions are cost-effective in routine primary care settings., Method: We conducted a systematic review of all full economic evaluations (cost-effectiveness and cost-utility analyses) accompanying randomised controlled trials of enhanced primary care for depression. Costs were standardised to UK pounds/US dollars and incremental cost-effectiveness ratios (ICERs) were visually summarised using a permutation matrix., Results: We identified 11 full economic evaluations (4757 patients). A near-uniform finding was that the interventions based upon collaborative care/case management resulted in improved outcomes but were also associated with greater costs. When considering primary care depression treatment costs alone, ICER estimates ranged from 7 ($13, no confidence interval given) to 13 UK pounds ($24,95% CI -105 to 148) per additional depression-free day. Educational interventions alone were associated with increased cost and no clinical benefit., Conclusions: Improved outcomes through depression management programmes using a collaborative care/case management approach can be expected, but are associated with increased cost and will require investment.

Context: Depression is commonly encountered in primary care settings yet is often missed or suboptimally managed. A number of organizational and educational strategies to improve management of depression have been proposed. The clinical effectiveness and cost-effectiveness of these strategies have not yet been subjected to systematic review., Objective: To systematically evaluate the effectiveness of organizational and educational interventions to improve the management of depression in primary care settings., Data Sources: We searched electronic medical and psychological databases from inception to March 2003 (MEDLINE, PsycLIT, EMBASE, CINAHL, Cochrane Controlled Trials Register, United Kingdom National Health Service Economic Evaluations Database, Cochrane Depression Anxiety and Neurosis Group register, and Cochrane Effective Professional and Organisational Change Group specialist register); conducted correspondence with authors; and used reference lists. Search terms were related to depression, primary care, and all guidelines and organizational and educational interventions., Study Selection: We selected 36 studies, including 29 randomized controlled trials and nonrandomized controlled clinical trials, 5 controlled before-and-after studies, and 2 interrupted time-series studies. Outcomes relating to management and outcome of depression were sought., Data Extraction: Methodological details and outcomes were extracted and checked by 2 reviewers. Summary relative risks were, where possible, calculated from original data and attempts were made to correct for unit of analysis error., Data Synthesis: A narrative synthesis was conducted. Twenty-one studies with positive results were found. Strategies effective in improving patient outcome generally were those with complex interventions that incorporated clinician education, an enhanced role of the nurse (nurse case management), and a greater degree of integration between primary and secondary care (consultation-liaison). Telephone medication counseling delivered by practice nurses or trained counselors was also effective. Simple guideline implementation and educational strategies were generally ineffective., Conclusions: There is substantial potential to improve the management of depression in primary care. Commonly used guidelines and educational strategies are likely to be ineffective. The implementation of the findings from this research will require substantial investment in primary care services and a major shift in the organization and provision of care.

Aims: Diabetes is two to three times more prevalent in people with severe mental illness, yet little is known about the challenges of managing both conditions from the perspectives of people living with the co‐morbidity, their family members or healthcare staff. Our aim was to understand these challenges and to explore the circumstances that influence access to and receipt of diabetes care for people with severe mental illness. Methods: Framework analysis of qualitative semi‐structured interviews with people with severe mental illness and diabetes, family members, and staff from UK primary care, mental health and diabetes services, selected using a maximum variation sampling strategy between April and December 2018. Results: In all, 39 adults with severe mental illness and diabetes (3 with type 1 diabetes and 36 with type 2 diabetes), nine family members and 30 healthcare staff participated. Five themes were identified: (a) Severe mental illness governs everyday life including diabetes management; (b) mood influences capacity and motivation for diabetes self‐management; (c) cumulative burden of managing multiple physical conditions; (d) interacting conditions and overlapping symptoms and (e) support for everyday challenges. People living with the co‐morbidity and their family members emphasised the importance of receiving support for the everyday challenges that impact diabetes management, and identified barriers to accessing this from healthcare providers. Conclusions: More intensive support for diabetes management is needed when people's severe mental illness (including symptoms of depression) or physical health deteriorates. Interventions that help people, including healthcare staff, distinguish between symptoms of diabetes and severe mental illness are also needed. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care. Methods: We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted. Results: Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions. Conclusions: When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression. [ABSTRACT FROM AUTHOR]

Importance: There is little evidence to guide management of depressive symptoms in older people.Objective: To evaluate whether a collaborative care intervention can reduce depressive symptoms and prevent more severe depression in older people.Design, Setting, and Participants: Randomized clinical trial conducted from May 24, 2011, to November 14, 2014, in 32 primary care centers in the United Kingdom among 705 participants aged 65 years or older with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) subthreshold depression; participants were followed up for 12 months.Interventions: Collaborative care (n=344) was coordinated by a case manager who assessed functional impairments relating to mood symptoms. Participants were offered behavioral activation and completed an average of 6 weekly sessions. The control group received usual primary care (n=361).Main Outcomes and Measures: The primary outcome was self-reported depression severity at 4-month follow-up on the 9-item Patient Health Questionnaire (PHQ-9; score range, 0-27). Included among 10 prespecified secondary outcomes were the PHQ-9 score at 12-month follow-up and the proportion meeting criteria for depressive disorder (PHQ-9 score ≥10) at 4- and 12-month follow-up.Results: The 705 participants were 58% female with a mean age of 77 (SD, 7.1) years. Four-month retention was 83%, with higher loss to follow-up in collaborative care (82/344 [24%]) vs usual care (37/361 [10%]). Collaborative care resulted in lower PHQ-9 scores vs usual care at 4-month follow-up (mean score with collaborative care, 5.36 vs with usual care, 6.67; mean difference, -1.31; 95% CI, -1.95 to -0.67; P < .001). Treatment differences remained at 12 months (mean PHQ-9 score with collaborative care, 5.93 vs with usual care, 7.25; mean difference, -1.33; 95% CI, -2.10 to -0.55). The proportions of participants meeting criteria for depression at 4-month follow-up were 17.2% (45/262) vs 23.5% (76/324), respectively (difference, -6.3% [95% CI, -12.8% to 0.2%]; relative risk, 0.83 [95% CI, 0.61-1.27]; P = .25) and at 12-month follow-up were 15.7% (37/235) vs 27.8% (79/284) (difference, -12.1% [95% CI, -19.1% to -5.1%]; relative risk, 0.65 [95% CI, 0.46-0.91]; P = .01).Conclusions and Relevance: Among older adults with subthreshold depression, collaborative care compared with usual care resulted in a statistically significant difference in depressive symptoms at 4-month follow-up, of uncertain clinical importance. Although differences persisted through 12 months, findings are limited by attrition, and further research is needed to assess longer-term efficacy.Trial Registration: isrctn.org Identifier: ISRCTN02202951. [ABSTRACT FROM AUTHOR]

Importance: Collaborative care is an intensive care model involving several health care professionals working together, typically a physician, a case manager, and a mental health professional. Meta-analyses of aggregate data have shown that collaborative care is particularly effective in people with depression and comorbid chronic physical conditions. However, only participant-level analyses can rigorously test whether the treatment effect is influenced by participant characteristics, such as chronic physical conditions.Objective: To assess whether the effectiveness of collaborative care for depression is moderated by the presence, type, and number of chronic physical conditions.Data Sources: Data were obtained from MEDLINE, EMBASE, PubMed, PsycINFO, CINAHL Complete, and Cochrane Central Register of Controlled Trials, and references from relevant systematic reviews. The search and collection of eligible studies was ongoing until May 22, 2015.Study Selection: This was an update to a previous meta-analysis. Two independent reviewers were involved in the study selection process. Randomized clinical trials that compared the effectiveness of collaborative care with usual care in adults with depression and reported measured changes in depression severity symptoms at 4 to 6 months after randomization were included in the analysis. Key search terms included depression, dysthymia, anxiety, panic, phobia, obsession, compulsion, posttraumatic, care management, case management, collaborative care, enhanced care, and managed care.Data Extraction and Synthesis: Individual participant data on baseline demographics and chronic physical conditions as well as baseline and follow-up depression severity symptoms were requested from authors of the eligible studies. One-step meta-analysis of individual participant data using appropriate mixed-effects models was performed.Main Outcomes and Measures: Continuous outcomes of depression severity symptoms measured using self-reported or observer-rated measures.Results: Data sets from 31 randomized clinical trials including 36 independent comparisons (N = 10 962 participants) were analyzed. Individual participant data analyses found no significant interaction effects, indicating that the presence (interaction coefficient, 0.02 [95% CI, -0.10 to 0.13]), numbers (interaction coefficient, 0.01 [95% CI, -0.01 to 0.02]), and types of chronic physical conditions do not influence the treatment effect.Conclusions and Relevance: There is evidence that collaborative care is effective for people with depression alone and also for people with depression and chronic physical conditions. Existing guidance that recommends limiting collaborative care to people with depression and physical comorbidities is not supported by this individual participant data meta-analysis. [ABSTRACT FROM AUTHOR]

Background The management of depression in primary care is a significant issue for health services worldwide. 'Collaborative care' interventions are effective, but little is known about which aspects of these complex interventions are essential. Aims To use meta-regression to identify 'active ingredients' in collaborative care models for depression in primary care. Method Studies were identified using systematic searches of electronic databases. The content of collaborative care interventions was coded, together with outcome data on antidepressant use and depressive symptoms. Meta-regression was used to examine relationships between intervention content and outcomes. Results There was no significant predictor of the effect of collaborative care on antidepressant use. Key predictors of depressive symptom outcomes included systematic identification of patients, professional background of staff and specialist supervision. Conclusions Meta-regression may be useful in examining 'active ingredients' in complex interventions in mental health. Declaration of interest None. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of research on the nature of life adversity in depressed and non-depressed older adults. Early life events work used in-depth interviews; however, larger epidemiological trials investigate life adversity using brief questionnaires. This study investigates the type of life adversity experienced in later life and its association with depression and compares adversity captured using a brief (LTE-Q) and in-depth (LEDS) measure.Methods: 960 participants over 65 years were recruited in UK primary care to complete the PHQ-9 and LTE-Q. A sub-sample (n=19) completed the LEDS and a question exploring the subjective experience of the LTE-Q and LEDS.Results: Important life adversity was reported on the LTE-Q in 48% of the sample. In the LTE-Q sample the prevalence of depression (PHQ-9≥10) was 12%. Exposure to recent adversity was associated with doubling of the odds of depression. The LTE-Q only captured a proportion of adversity measured by the LEDS (42% vs 84%). Both measures showed health, bereavement and relationship events were most common.Limitations: The cross-sectional design limits the extent to which inferences can be drawn around the direction of causality between adversity and depression. Recall in older adults is questionable.Conclusions: UK older adults face adversity in areas of health, bereavement and relationships which are associated with depression. This has clinical relevance for psychological interventions for older adults to consider social context and social support. It helps identify the strengths and weaknesses of a brief adversity measure in large scale research. Further research is needed to explore the mechanisms of onset and direction of causality. [ABSTRACT FROM AUTHOR]