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Background: Current treatment guidelines advise that the deprescribing of antidepressants should occur around 6 months post-remission of symptoms. However, this is not routinely occurring in clinical practice, with between 30% and 50% of antidepressant users potentially continuing treatment with no clinical benefit. To support patients to deprescribe antidepressant treatment when clinically appropriate, it is important to understand what is important to patients when making the decision to reduce or cease antidepressants in a naturalistic setting. Aim: The current study aimed to describe the self-reported reasons primary care patients have for reducing or stopping their antidepressant medication. Methods: Three hundred and seven participants in the diamond longitudinal study reported taking an SSRI/SNRI over the life of the study. Of the 307, 179 reported stopping or tapering their antidepressant during computer-assisted telephone interviews and provided a reason for doing so. A collective case study approach was used to collate the reasons for stopping or tapering. Findings: Reflexive thematic analysis of patient-reported factors revealed five overarching themes; 1. Depression; 2. Medication; 3. Healthcare system; 4. Psychosocial, and; 5. Financial. These findings are used to inform suggestions for the development and implementation of antidepressant deprescribing discussions in clinical practice.

BACKGROUND Research suggests that the rapid increase in worldwide antidepressant use is mainly due to a rise in long-term and potentially inappropriate use. General practice patients who are no longer experiencing clinical benefit from their medication, should commence deprescribing. However this process is complex for both patients and clinicians and is not routinely occurring. Evidence based support for safe and successful antidepressant deprescribing is needed for patients and their doctor. OBJECTIVE This study aims to evaluate how the WiserAD approach to antidepressant deprescribing works, for whom and in what circumstances. METHODS A mixed methods case study realist evaluation will be conducted on participants in the WiserAD randomised controlled trial for antidepressant deprescribing. Up to 12 participants from the intervention and control arms will provide quantitative data at baseline and 3-month follow-up. Qualitative data from the same participants will be collected via narrative interview at 3-month follow-up. Quantitative and qualitative data will be converged to form a ‘case’ and analysis will be conducted within each case with comparisons made across multiple cases. RESULTS Recruitment of participants will commence in late 2022 and completed in early 2023. CONCLUSIONS To our knowledge, this will be the first realist evaluation of an antidepressant deprescribing intervention in primary care. Findings from this evaluation may assist in the implementation of antidepressant deprescribing in clinical practice. CLINICALTRIAL N/A

BACKGROUND Depression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment—a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses. OBJECTIVE The aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment. METHODS The study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity. RESULTS Recruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023. CONCLUSIONS This trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients. CLINICALTRIAL ISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/31925

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Background Effective help for depression and anxiety reaches a small proportion of people who might benefit from it. The scale of the problem suggests the need for effective, safe web-based public health services delivered directly to the public. One model, the Big White Wall (BWW), offers peer support at low cost. As these interventions are delivered digitally, we tested whether a randomized controlled trial (RCT) intervention could also be fully delivered and evaluated digitally. Objective This study aims to determine the reach, feasibility, acceptability, baseline costs, and outcomes of a public health campaign for an automated RCT of the BWW, providing digital peer support and information, compared with a standard website used by the National Health Service Moodzone (MZ), to people with probable mild-to-moderate depression and anxiety disorder. The primary outcome was the change in self-rated well-being at 6 weeks, measured using the Warwick-Edinburgh Mental Well-Being Scale. Methods An 18-month campaign was conducted across Nottinghamshire, the United Kingdom (target population 914,000) to advertise the trial directly to the public through general marketing, web-based and social media sources, health services, other public services, and third-sector groups. The population reach of this campaign was examined by the number of people accessing the study website and self-registering to the study. A pragmatic, parallel-group, single-blind RCT was then conducted using a fully automated trial website in which eligible participants were randomized to receive either 6 months of access to BWW or signposted to MZ. Those eligible for participation were aged >16 years with probable mild-to-moderate depression or anxiety disorders. Results Of 6483 visitors to the study website, 1510 (23.29%) were eligible. Overall, 790 of 1510 (52.32%) visitors participated. Of 790 visitors, 397 (50.3%) were randomized to BWW and 393 (49.7%) to MZ. Their mean age was 38 (SD 13.8) years, 81.0% (640/790) were female, 93.4% (738/790) were White, and 47.4% (271/572) had no contact with health services in the previous 3 months. We estimated 3-month productivity losses of £1001.01 (95% CI 868.75-1133.27; US $1380.79; 95% CI 1198.35-1563.23) per person for those employed. Only 16.6% (131/790) participants completed the primary outcome assessment. There were no differences in the primary or secondary outcomes between the 2 groups. Conclusions Most participants reached and those eligible for this trial of digital interventions were White women not in recent contact with health services and whose productivity losses represent a significant annual societal burden. A fully automated RCT recruiting directly from the public failed to recruit and retain sufficient participants to test the clinical effectiveness of this digital intervention, primarily because it did not personally engage participants and explain how these unfamiliar interventions might benefit them. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN) 12673428; https://www.isrctn.com/ISRCTN12673428 International Registered Report Identifier (IRRID) RR2-10.2196/resprot.8061

BACKGROUND Effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe public health online services delivered directly to the public. One model is Big White Wall, which offers peer support at low cost. Since these interventions are delivered digitally, we tested whether a randomised controlled trial (RCT) intervention could also be fully delivered and evaluated digitally. OBJECTIVE To determine the reach, feasibility, acceptability, baseline costs and outcomes of a public health campaign for an automated randomised controlled trial of Big White Wall (BWW) providing digital peer support and information, compared with a standard website used by the National Health Service (NHS Choices Moodzone, MZ) in people with probable mild to moderate depression and anxiety disorder. The primary outcome was change in self-rated well-being at 6 weeks, measured by the Warwick-Edinburgh Mental Well-Being Scale. METHODS An 18 month campaign was performed across Nottinghamshire, United Kingdom (target population 914,000) to advertise the trial direct to the public through general marketing, online and social media sources, health services, other public services and third sector groups. The population reach of this campaign was examined by numbers accessing the study website and self-registering to the study. A pragmatic, parallel group, single blind RCT (ISRCTN ) was then conducted using a fully automated trial website in which eligible participants were randomised to receive either 6 months access to BWW or signposted to MZ. Those eligible for participation were over 16 years with probable mild to moderate depression or anxiety disorders. RESULTS Of 6483 visitors to the study website, only 1,510 were eligible. 790 (52.3% of eligible) participated, 397 randomised to BWW and 393 to MZ. Their mean age (sd) was 38.0 (13.8) years, 640 (82.0%) were female, 738 (93.7%) were white, all had educational qualifications, and 271 (47.4%) had no contact with health services in the previous three months. We estimated 3-month productivity losses of £1019.05 (1057.70) per person for those employed. Only 131 (16.6%) participants completed the primary outcome assessment. There were no differences in primary nor secondary outcomes between the two groups. CONCLUSIONS Most participants reached and eligible for this trial of digital intervention providing information and/or support for mild to moderate depression and anxiety were educated women of white ethnicity not in recent contact with health services, and whose productivity losses represent a significant annual societal burden A fully automated RCT recruiting directly from the public failed to recruit and retain sufficient participants to test the clinical effectiveness of this digital intervention. CLINICALTRIAL International Standard Randomized Controlled Trial Number (ISRCTN) 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428. INTERNATIONAL REGISTERED REPORT RR2-10.2196/resprot.8061

Background Self-harm and depression are strong risk factors for repeat self-harm and suicide. We aimed to investigate the feasibility of a randomised controlled trial (RCT) of remotely delivered problem-solving cognitive behaviour therapy (PSCBT) plus treatment as usual (TAU) versus TAU in young people with repeat self-harm and depression. Methods Single-blind multi-centre RCT with an internal pilot, pre-set stop-go criteria and qualitative semi-structured interviews. Eligible participants (aged 16–30 years) were recruited from 9 adult or child and adolescent self-harm and crisis services; had ≥ 2 lifetime self-harm episodes, one in the preceding 96 h; and Beck Depression Inventory-II (BDI-II) score ≥ 17. Participants were randomised (1:1) to either TAU or TAU and 10–12 sessions of PSCBT delivered by mobile phone or video-calling. Results Twenty-two participants were recruited (11 in each arm), 10 (46%) completed follow-up at 6 months, 9 (82%) started the PSCBT and 4 (36%) completed it. The study did not meet three of its four stop-go criteria, reflecting considerable barriers to recruitment and retention. Participants had severe depression symptoms: with mean BDI-II 38.9 in the PSCBT and 37.2 in TAU groups, respectively. Three (14%) unblindings occurred for immediate safety concerns. Barriers to recruitment and retention included lack of agency for participants, severity of depression, recency of crisis with burden for participants and clinicians who diagnosed depression according to pervasiveness. Conclusions RCTs of PSCBT for young people with depression and self-harm are not feasible using recruitment through mental health services that conduct assessments following self-harm presentations. Clinician assessment following self-harm presentation mainly identifies those with severe rather than mild-moderate depression. Trial registration ClinicalTrials.gov (NCT02377011); Date of registration: March 3rd 2015. Retrospectively registered: within 21 days of recruitment of the first participant. Electronic supplementary material The online version of this article (10.1186/s12888-018-2005-3) contains supplementary material, which is available to authorized users.

Background: The Patient Health Questionnaire-9 (PHQ-9) is a widely used instrument for measuring levels of depression in patients in clinical practice and academic research; its factor structure has been investigated in various samples, with limited evidence of measurement equivalence/invariance (ME/I) but not in patients with more severe depression of long duration. This study aims to explore the factor structure of the PHQ-9 and the ME/I between treatment groups over time for these patients. Methods: 187 secondary care patients with persistent major depressive disorder (PMDD) were recruited to a randomised controlled trial (RCT) with allocation to either a specialist depression team arm or a general mental health arm; their PHQ-9 score was measured at baseline, 3, 6, 9 and 12 months. Exploratory Structural Equational Modelling (ESEM) was performed to examine the factor structure for this specific patient group. ME/I between treatment arm at and across follow-up time were further explored by means of multiple-group ESEM approach using the best-fitted factor structure. Results: A two-factor structure was evidenced (somatic and affective factor). This two-factor structure had strong factorial invariance between the treatment groups at and across follow up times. Limitations: Participants were largely white British in a RCT with 40% attrition potentially limiting the study’s generalisability. Not all two-factor modelling criteria were met at every time-point. Conclusion: PHQ-9 has a two-factor structure for PMDD patients, with strong measurement invariance between treatment groups at and across follow-up time, demonstrating its validity for RCTs and prospective longitudinal studies in chronic moderate to severe depression.

BackgroundThe 17-item Hamilton Depression Rating Scale (HDRS17) is used world-wide as an observer-rated measure of depression in randomised controlled trials (RCTs) despite continued uncertainty regarding its factor structure. This study investigated the dimensionality of HDRS17 for patients undergoing treatment in UK mental health settings with moderate to severe persistent major depressive disorder (PMDD).MethodsExploratory Structural Equational Modelling (ESEM) was performed to examine the HDRS17 factor structure for adult PMDD patients with HDRS17 score ≥16. Participants (n = 187) were drawn from a multicentre RCT conducted in UK community mental health settings evaluating the outcomes of a depression service comprising CBT and psychopharmacology within a collaborative care model, against treatment as usual (TAU). The construct stability across a 12-month follow-up was examined through a measurement equivalence/invariance (ME/I) procedure via ESEM.ResultsESEM showed HDRS17 had a bi-factor structure for PMDD patients (baseline mean (sd) HDRS17 22.6 (5.2); 87% PMDD >1 year) with an overall depression factor and two group factors: vegetative-worry and retardation-agitation, further complicated by negative item loading. This bi-factor structure was stable over 12 months follow up. Analysis of the HDRS6 showed it had a unidimensional structure, with positive item loading also stable over 12 months.ConclusionsIn this cohort of moderate-severe PMDD the HDRS17 had a bi-factor structure stable across 12 months with negative item loading on domain specific factors, indicating that it may be more appropriate to multidimensional assessment of settled clinical states, with shorter unidimensional subscales such as the HDRS6 used as measures of change.

© 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health. Background: Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. Methods: Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6–17years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). Results: One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04–2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77–0.93), increased clinicians’ confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09–2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as ‘cost neutral’. Conclusions: QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy.

BackgroundHealth anxiety and medically unexplained symptoms cost the National Health Service (NHS) an estimated £3 billion per year in unnecessary costs with little evidence of patient benefit. Effective treatment is rarely taken up due to issues such as stigma or previous negative experiences with mental health services. An approach to overcome this might be to offer remotely delivered psychological therapy, which can be just as effective as face-to-face therapy and may be more accessible and suitable.AimsTo investigate the clinical outcomes and cost-effectiveness of remotely delivered cognitive–behavioural therapy (CBT) to people with high health anxiety repeatedly accessing unscheduled care (trial registration: NCT02298036).MethodA multicentre randomised controlled trial (RCT) will be undertaken in primary and secondary care providers of unscheduled care across the East Midlands. One hundred and forty-four eligible participants will be equally randomised to receive either remote CBT (6–12 sessions) or treatment as usual (TAU). Two doctoral research studies will investigate the barriers and facilitators to delivering the intervention and the factors contributing to the optimisation of therapeutic outcome.ResultsThis trial will be the first to test the clinical outcomes and cost-effectiveness of remotely delivered CBT for the treatment of high health anxiety.ConclusionsThe findings will enable an understanding as to how this intervention might fit into a wider care pathway to enhance patient experience of care.

A specialist depression service (SDS) offering collaborative pharmacological and cognitive behaviour therapy treatment for persistent depressive disorder showed effectiveness against depression symptoms versus usual community based multidisciplinary care in a randomised controlled trial (RCT) in specialist mental health services in England. However, there is uncertainty concerning how specialist depression services effect such change. The current study aimed to evaluate the factors which may explain the greater effectiveness of SDS compared to Treatment as Usual (TAU) by exploring the experience of the RCT participants. Qualitative audiotaped and transcribed semi-structured interviews were conducted 12–18 months after baseline with 21 service users (12 SDS, 9 TAU arms) drawn from all three sites. Inductive thematic analysis using a grounded approach contrasted the experiences of SDS with TAU participants. Four themes emerged in relation to service user experience: 1. Specific treatment components of the SDS: which included sub-themes of the management of medication change, explaining and developing treatment strategies, setting realistic expectations, and person-centred and holistic approach; 2. Individual qualities of SDS clinicians; 3. Collaborative team context in SDS: which included sub-themes of communication between healthcare professionals, and continuity of team members; 4. Accessibility to SDS: which included sub-themes of flexibility of locations, frequent consultation as reinforcement, gradual pace of treatment, and challenges of returning to usual care. The study uncovered important mechanisms and contextual factors in the SDS that service users experience as different from TAU, and which may explain the greater effectiveness of the SDS: the technical expertise of the healthcare professionals, personal qualities of clinicians, teamwork, gradual pace of care, accessibility and managing service transitions. Usual care in other specialist mental health services may share many of the features from the SDS. “Trial of the Clinical and Cost Effectiveness of a Specialist Expert Mood Disorder Team for Refractory Unipolar Depressive Disorder” was registered in www.ClinicalTrials.gov ( NCT01047124 ) on 12–01-2010 and the ISRCTN registry was registered in www.isrctn.com ( ISRCTN10963342 ) on 25–11-2015 (retrospectively registered).

Background Regardless of geography or income, effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe, anonymized public health–driven Web-based services such as Big White Wall (BWW), which offer immediate peer support at low cost. Objective Using Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) methodology, the aim of this study was to determine the population reach, effectiveness, cost-effectiveness, and barriers and drivers to implementation of BWW compared with Web-based information compiled by UK’s National Health Service (NHS, NHS Choices Moodzone) in people with probable mild to moderate depression and anxiety disorder. Methods A pragmatic, parallel-group, single-blind randomized controlled trial (RCT) is being conducted using a fully automated trial website in which eligible participants are randomized to receive either 6 months access to BWW or signposted to the NHS Moodzone site. The recruitment of 2200 people to the study will be facilitated by a public health engagement campaign involving general marketing and social media, primary care clinical champions, health care staff, large employers, and third sector groups. People will refer themselves to the study and will be eligible if they are older than 16 years, have probable mild to moderate depression or anxiety disorders, and have access to the Internet. Results The primary outcome will be the Warwick-Edinburgh Mental Well-Being Scale at 6 weeks. We will also explore the reach, maintenance, cost-effectiveness, and barriers and drivers to implementation and possible mechanisms of actions using a range of qualitative and quantitative methods. Conclusions This will be the first fully digital trial of a direct to public online peer support program for common mental disorders. The potential advantages of adding this to current NHS mental health services and the challenges of designing a public health campaign and RCT of two digital interventions using a fully automated digital enrollment and data collection process are considered for people with depression and anxiety. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428 (Archived by WebCite at http://www.webcitation.org/6uw6ZJk5a)

BACKGROUND Regardless of geography or income, effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe, anonymized public health–driven Web-based services such as Big White Wall (BWW), which offer immediate peer support at low cost. OBJECTIVE Using Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) methodology, the aim of this study was to determine the population reach, effectiveness, cost-effectiveness, and barriers and drivers to implementation of BWW compared with Web-based information compiled by UK’s National Health Service (NHS, NHS Choices Moodzone) in people with probable mild to moderate depression and anxiety disorder. METHODS A pragmatic, parallel-group, single-blind randomized controlled trial (RCT) is being conducted using a fully automated trial website in which eligible participants are randomized to receive either 6 months access to BWW or signposted to the NHS Moodzone site. The recruitment of 2200 people to the study will be facilitated by a public health engagement campaign involving general marketing and social media, primary care clinical champions, health care staff, large employers, and third sector groups. People will refer themselves to the study and will be eligible if they are older than 16 years, have probable mild to moderate depression or anxiety disorders, and have access to the Internet. RESULTS The primary outcome will be the Warwick-Edinburgh Mental Well-Being Scale at 6 weeks. We will also explore the reach, maintenance, cost-effectiveness, and barriers and drivers to implementation and possible mechanisms of actions using a range of qualitative and quantitative methods. CONCLUSIONS This will be the first fully digital trial of a direct to public online peer support program for common mental disorders. The potential advantages of adding this to current NHS mental health services and the challenges of designing a public health campaign and RCT of two digital interventions using a fully automated digital enrollment and data collection process are considered for people with depression and anxiety. CLINICALTRIAL International Standard Randomized Controlled Trial Number (ISRCTN): 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428 (Archived by WebCite at http://www.webcitation.org/6uw6ZJk5a)

Summary Background Persistent moderate or severe unipolar depression is common and expensive to treat. Clinical guidelines recommend combined pharmacotherapy and psychotherapy. Such treatments can take up to 1 year to show an effect, but no trials of suitable duration have been done. We investigated the efficacy and cost-effectiveness of outpatient-based, specialist depression services (SDS) versus treatment as usual (TAU) on depression symptoms and function. Methods We did a multicentre, single-blind, patient-level, parallel, randomised controlled trial (RCT), as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) study, in three mental health outpatient settings in England. Eligible participants were in secondary care, were older than 18 years, had unipolar depression (with a current major depressive episode, a 17-item Hamilton Depression Rating Scale [HDRS 17 ] score of ≥16, and a Global Assessment of Function [GAF] score of ≤60), and had not responded to 6 months or more of treatment for depression. Randomisation was stratified by site with allocation conveyed to a trial administrator, with research assessors masked to outcome. Patients were randomised (1:1) using a computer-generated pseudo-random code with random permuted blocks of varying sizes of two, four, or six to either SDS (collaborative care approach between psychiatrists and cognitive behavioural therapists for 12 months, followed by graduated transfer of care up to 15 months) or to the TAU group. Intention-to-treat primary outcome measures were changes in HDRS 17 and GAF scores between baseline and 6, 12, and 18 months' follow-up. We will separately publish follow-up outcomes for months 24 and 36. Clinical efficacy and cost-effectiveness were examined from health and social care persp ectives at 18 months, as recommended by the National Institute for Health and Care Excellence. This trial is registered at ClinicalTrials.gov (NCT01047124) and the ISRCTN registry (ISRCTN10963342); the trial has ended. Findings 307 patients were assessed for eligibility between Dec 21, 2009, and Oct 31, 2012. 94 patients were assigned to TAU and 93 patients to SDS, and were included in intention-to-treat analyses. The changes from baseline to 6 months in HDRS 17 and GAF scores did not significantly differ between treatment groups (mean change difference in HDRS 17 score −1·01 [95% CI −3·30 to 1·28], p=0·385; and in GAF score 1·33 [–2·92 to 5·57], p=0·538). Primary outcome data were available for 134 (72%) patients at 12 months. We noted no differences at 12 months' follow-up between SDS and TAU for mean HDRS 17 score (14·8 [SD 7·9] in the SDS group vs 17·2 [7·3] in the TAU group, p=0·056) or GAF score (60·4 [11·7] vs 55·8 [12·7], p=0·064), and the changes from baseline to 12 months in HDRS 17 and GAF scores did not significantly differ between treatment groups (mean change difference in HDRS 17 score −2·45 [95% CI −5·04 to 0·14], p=0·064; and in GAF score 4·12 [–0·11 to 8·35], p=0·056). The mean change in HDRS 17 score from baseline to 18 months was significantly improved in the SDS group compared with the TAU group (13·6 [SD 8·8] in the SDS group vs 16·1 [6·6] in the TAU group; mean change difference −2·96 [95% CI −5·33 to −0·59], p=0·015), but the GAF scores showed no significant differences between the groups (61·2 [SD 13·0] vs 57·7 [11·9]; mean change difference 3·82 [–9·3 to 8·57], p=0·113). We reported no deaths, but one (1%) patient was admitted to hospital for myocardial infarction, and three episodes of self-harm were reported in three (2%) patients (two receiving TAU, one receiving SDS care). The incremental cost-effectiveness ratio of SDS versus TAU was £43 603 per quality-adjusted life-year. Interpretation Compared with usual specialist mental health secondary care, SDS might improve depression symptoms for patients with persistent moderate to severe depression, but functional outcomes and economic benefits are equivocal. Funding National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care, UK Medical Research Council, Nottinghamshire Healthcare NHS Foundation Trust, Derbyshire Healthcare NHS Foundation Trust, Cambridgeshire and Peterborough NHS Foundation Trust, University of Nottingham.

Background A recently emergent functional neuroimaging literature has described the functional anatomical correlates of deception among healthy volunteers, most often implicating the ventrolateral prefrontal and anterior cingulate cortices. To date, there have been no such imaging studies of people with severe mental illness. Aims To discover whether the brains of people with schizophrenia would manifest a similar functional anatomical distinction between the states of truthfulness and deceit. It is hypothesised that, as with healthy people, persons with schizophrenia will show activation in the ventrolateral prefrontal and anterior cingulate cortices when lying. Method Fifty-two people satisfying Diagnostic and Statistical Manual of Mental Disorder-IV criteria for schizophrenia or schizoaffective disorder underwent functional magnetic resonance imaging at 3 T while responding truthfully or with lies to questions concerning their recent actions. Half the sample was concurrently experiencing delusions. Results As hypothesised, patients exhibited greater activity in ventrolateral prefrontal cortices while lying. Truthful responses were not associated with any areas of relatively increased activation. The presence or absence of delusions did not substantially affect these findings, although subtle laterality effects were discernible upon post hoc analyses. Conclusions As in healthy cohorts, the brains of people with schizophrenia exhibit a functional anatomical distinction between the states of truthfulness and deceit. Furthermore, this distinction pertains even in the presence of delusions. Copyright © 2010 John Wiley & Sons, Ltd.

Free association has been central to psychoanalytic theory and practice for over a century, yet its physiology has largely been ignored. When viewed from a cognitive neurobiological perspective, the process resembles a minimally constrained executive task, one that might engage the left dorsolateral prefrontal cortex. To test this hypothesis, we used functional magnetic resonance imaging to detect neural activity while subjects performed overt, vocal free association in the scanner. Twelve healthy subjects performed three active tasks—vocal free association, orthographic (letter) fluency, and semantic (category) fluency—alternating with a baseline condition, word repetition. Stimulus administration and overt response performance occurred during periods of scanner silence. Each subject was scanned three times, the order of conditions counterbalanced across scans. Statistical parametric mapping was used to perform a mixed-effects analysis of those images acquired. We found that, in common with both verbal f...

ResumenEl “síndrome de Munchausen por poderes” se refiere, en general, a mujeres acusadas de haber inventado o producido enfermedades en niños bajo su cuidado, destinadas a atraer la atención sobre sí misma. Cuando hay pruebas concluyentes, hay dudas sobre la etiología de la enfermedad, pero cuando no hay pruebas, el diagnóstico depende de la negación de la intencionalidad (conducta también compatible con la inocencia). ¿Cómo podrían los investigadores conseguir pruebas objetivas sobre culpabilidad o inocencia? En este artículo analizamos el caso de una mujer condenada por envenenar a su hija. Cumplió la condena en la cárcel, pero sigue reclamando su inocencia. Usando un protocolo modificado de RMf (publicado ya en 2001) realizamos la prueba de neuroimagen mientras ella confirmaba su versión de los acontecimientos y mientras aceptaba la de sus acusadores. Sugerimos la hipótesis de que los tiempos de respuesta serían más largos y se asociaran con mayor activación de la corteza cingular anterior y prefrontal ventrolateral cuando hacía declaraciones falsas (es decir, cuando “mentía”). La mujer fue sometida 4 veces a RM de 3 teslas. Los resultados revelaron tiempos de respuesta considerablemente más largos y un activación relativamente mayor de la corteza cingular anterior y prefrontal ventrolateral cuando aceptaba la versión de los acontecimientos de sus acusadores. Es decir que aunque no hemos “probado” que esta mujer es inocente, demostramos que sus parámetros conductuales y funcionales anatómicos se comportan como si lo fuera.

‘Munchausen's syndrome by proxy’ characteristically describes women alleged to have fabricated or induced illnesses in children under their care, purportedly to attract attention. Where conclusive evidence exists the condition's aetiology remains speculative, where such evidence is lacking diagnosis hinges upon denial of wrong-doing (conduct also compatible with innocence). How might investigators obtain objective evidence of guilt or innocence? Here, we examine the case of a woman convicted of poisoning a child. She served a prison sentence but continues to profess her innocence. Using a modified fMRI protocol (previously published in 2001) we scanned the subject while she affirmed her account of events and that of her accusers. We hypothesized that she would exhibit longer response times in association with greater activation of ventrolateral prefrontal and anterior cingulate cortices when endorsing those statements she believed to be false (i.e., when she ‘lied’). The subject was scanned 4 times at 3 Tesla. Results revealed significantly longer response times and relatively greater activation of ventrolateral prefrontal and anterior cingulate cortices when she endorsed her accusers' version of events. Hence, while we have not ‘proven’ that this subject is innocent, we demonstrate that her behavioural and functional anatomical parameters behave as if she were.

Lying is ubiquitous and has acquired many names. In 'natural experiments', both pathological lying and truthfulness implicate prefrontal cortices. Recently, the advent of functional neuroimaging has allowed investigators to study deception in the non-pathological state. Prefrontal cortices are again implicated, although the regions identified vary across experiments. Forensic application of such technology (to the detection of deceit) requires the solution of tractable technical problems. Whether we 'should' detect deception remains an ethical problem: one for societies to resolve. However, such a procedure would only appear to be ethical when subjects volunteer to participate, as might occur during the investigation of alleged miscarriages of justice. We demonstrate how this might be approached.

Behavioural and functional anatomical responses exhibited by humans support the hypothesis that deception involves the prefrontal executive. Functional neuroimaging studies have demonstrated that ventrolateral prefrontal cortex (among other areas) is activated during lying, compared with telling the truth. However, despite some consistencies discernible across studies, problems remain concerning experimental validity, e.g., the expediencies of experimenter-sanctioned cued-deception (i.e., subjects being told when to lie); such 'lies' may not have comprised adequate proxies for 'real-life' deception. In this experiment, we attempted to address such confounding issues by designing an fMRI paradigm in which subjects chose when to lie (thereby minimising cue-dependency), using spoken words, concerning intimate material, which they regarded as 'embarrassing'; and where further control conditions required them to 'comply' with their examiners or to 'defy' them (by withholding pre-specified responses). The main effect of lying revealed significant activation of ventrolateral prefrontal cortices. These results replicate and extend our previous findings to those circumstances under which subjects are allowed to choose when to deceive.

Introduction: The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current ‘gold standard’ ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. Methods and analysis: This multisite randomised controlled trial will recruit young people (aged 6–17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. Ethics and dissemination: The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval.

Background Around 40 per cent of patients with unipolar depressive disorder who are treated in secondary care mental health services do not respond to first or second line treatments for depression. Such patients have 20 times the suicide rate of the general population and treatment response becomes harder to achieve and sustain the longer they remain depressed. Despite this there are no randomised controlled trials of community based service delivery interventions delivering both algorithm based pharmacotherapy and psychotherapy for patients with chronic depressive disorder in secondary care mental health services who remain moderately or severely depressed after six months treatment. Without such trials evidence based guidelines on services for such patients cannot be derived. Methods/design Single blind individually randomised controlled trial of a specialist depression disorder team (psychiatrist and psychotherapist jointly assessing and providing algorithm based drug and psychological treatment) versus usual secondary care treatment. We will recruit 174 patients with unipolar depressive disorder in secondary mental health services with a Hamilton Depression Rating Scale (HDRS) score ≥ 16 and global assessment of function (GAF) ≤ 60 after ≥ 6 months treatment. The primary outcome measures will be the HDRS and GAF supplemented by economic analysis incuding the EQ5 D and analysis of barriers to care, implementation and the process of care. Audits to benchmark both treatment arms against national standards of care will aid the interpretation of the results of the study. Discussion This trial will be the first to assess the effectiveness and implementation of a community based specialist depression disorder team. The study has been specially designed as part of the CLAHRC Nottinghamshire, Derbyshire and Lincolnshire joint collaboration between university, health and social care organisations to provide information of direct relevance to decisions on commissioning, service provision and implementation. Trial registration Clinical trials.gov identifier NCT01047124