CLEAR - clozapine in early psychosis: study protocol for a multi-centre, randomised controlled trial of clozapine vs other antipsychotics for young people with treatment resistant schizophrenia in real world settings.

BACKGROUND: Clozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. METHODS AND DESIGN: This is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12-24 years old). AIM AND OBJECTIVES: The primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. DISCUSSION: The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis. TRIAL REGISTRATION: ISRCTN Number: 37176025, IRAS Number: 1004947. TRIAL STATUS: In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.

Assertive outreach treatment versus care as usual for the treatment of high-need, high-cost alcohol related frequent attenders: study protocol for a randomised controlled trial.

BACKGROUND: Alcohol-related hospital admissions have doubled in the last ten years to > 1.2 m per year in England. High-need, high-cost (HNHC) alcohol-related frequent attenders (ARFA) are a relatively small subgroup of patients, having multiple admissions or attendances from alcohol during a short time period. This trial aims to test the effectiveness of an assertive outreach treatment (AOT) approach in improving clinical outcomes for ARFA, and reducing resource use in the acute setting. METHODS: One hundred and sixty ARFA patients will be recruited and following baseline assessment, randomly assigned to AOT plus care as usual (CAU) or CAU alone in equal numbers. Baseline assessment includes alcohol consumption and related problems, physical and mental health comorbidity and health and social care service use in the previous 6 months using standard validated tools, plus a measure of resource use. Follow-up assessments at 6 and 12 months after randomization includes the same tools as baseline plus standard measure of patient satisfaction. Outcomes for CAU + AOT and CAU at 6 and 12 months will be compared, controlling for pre-specified baseline measures. Primary outcome will be percentage of days abstinent at 12 months. Secondary outcomes include emergency department (ED) attendance, number and length of hospital admissions, alcohol consumption, alcohol-related problems, other health service use, mental and physical comorbidity 6 and 12 months post intervention. Health economic analysis will estimate the economic impact of AOT from health, social care and societal perspectives and explore cost-effectiveness in terms of quality adjusted life years and alcohol consumption at 12-month follow-up. DISCUSSION: AOT models piloted with alcohol dependent patients have demonstrated significant reductions in alcohol consumption and use of unplanned National Health Service (NHS) care, with increased engagement with alcohol treatment services, compared with patients receiving CAU. While AOT interventions are costlier per case than current standard care in the UK, the rationale for targeting HNHC ARFAs is because of their disproportionate contribution to overall alcohol burden on the NHS. No previous studies have evaluated the clinical and cost-effectiveness of AOT for HNHC ARFAs: this randomized controlled trial (RCT) targeting ARFAs across five South London NHS Trusts is the first. TRIAL REGISTRATION: International standard randomized controlled trial number (ISRCTN) registry: ISRCTN67000214, retrospectively registered 26/11/2016.

An exploratory parallel-group randomised controlled trial of antenatal Guided Self-Help (plus usual care) versus usual care alone for pregnant women with depression: DAWN trial.

BACKGROUND: Depression is a common antenatal mental disorder associated with significant maternal morbidity and adverse fetal outcomes. However, there is a lack of research on the effectiveness or cost-effectiveness of psychological interventions for antenatal depression. METHODS: A parallel-group, exploratory randomised controlled trial across five hospitals. The trial compared Guided Self-Help, modified for pregnancy, plus usual care with usual care alone for pregnant women meeting DSM-IV criteria for mild-moderate depression. The trial objectives were to establish recruitment/follow-up rates, compliance and acceptability, and to provide preliminary evidence of intervention efficacy and cost-effectiveness. The primary outcome of depressive symptoms was assessed by blinded researchers using the Edinburgh Postnatal Depression Scale at 14-weeks post-randomisation. RESULTS: 620 women were screened, 114 women were eligible and 53 (46.5%) were randomised. 26 women received Guided Self-Help - 18 (69%) attending ≥4 sessions - and 27 usual care; n = 3 women were lost to follow-up (follow-up rate for primary outcome 92%). Women receiving Guided Self-Help reported fewer depressive symptoms at follow-up than women receiving usual care (adjusted effect size -0.64 (95%CI: -1.30, 0.06) p = 0.07). There were no trial-related adverse events. The cost-effectiveness acceptability curve showed the probability of Guided Self-Help being cost-effective compared with usual care ranged from 10 to 50% with a willingness-to-pay range from £0 to £50,000. CONCLUSIONS AND LIMITATIONS: Despite intense efforts we did not meet our anticipated recruitment target. However, high levels of acceptability, a lack of adverse events and a trend towards improvements in symptoms of depression post-treatment indicates this intervention is suitable for talking therapy services.

Moderators and predictors of outcomes in telephone delivered compared to face-to-face cognitive behaviour therapy for paediatric obsessive-compulsive disorder: preliminary evidence from a non-inferiority RCT.

This study provides a preliminary exploration of factors which differentially predict treatment response to telephone-delivered cognitive behavioural therapy (TCBT) compared to face-to-face CBT (CBT) in a randomised non-inferiority controlled trial of 72 children (aged 11-18 years) with obsessive-compulsive disorder (OCD). Potential moderator variables, their interaction with treatment group (CBT, TCBT) and baseline levels of OCD severity were entered into separate regression models where the primary outcome measure was the post-intervention Children's Yale-Brown Obsessive-Compulsive Scale total score (CYBOCS). Separate regressions were also used to test associations between predictors and outcome controlling for pretreatment CYBOCS. Only pretreatment level of parent-rated child peer problems moderated the effects of the two interventions on CYBOCS severity at post-treatment. After controlling for baseline CYBOCS, only family accommodation rated by mothers predicted poorer outcomes in both groups. While CBT and TCBT may be equally effective for adolescents with OCD, the current results tentatively suggest that higher baseline level of peer problems strengthened the response to therapy for youth receiving TCBT and the predictor analyses reinforce the importance of directly addressing family accommodation during CBT for paediatric OCD regardless of delivery mode. Limitations of the current findings and directions for future work are discussed.

Psychological distress among primary school teachers: a comparison with clinical and population samples.

OBJECTIVES: This analysis explored the level of psychological distress among primary school teachers in the South West of England as compared with clinical and general population samples. STUDY DESIGN: Secondary analysis of data from the Supporting Teachers and Children in Schools (STARS) trial completed by up to 90 teachers at baseline, 9, 18 and 30 months of follow-up. METHODS: We used the Everyday Feelings Questionnaire (EFQ) as a measure of psychological distress. Baseline data on teachers were compared with a population sample of professionals and a clinical sample of patients attending a depression clinic. RESULTS: Our teacher cohort experienced higher levels of psychological distress than comparable professionals from the general population, which were sustained over 30 months of follow-up. Levels of psychological distress were lower than those found in the clinical sample. Using a cut-point indicative of moderate depression, our data suggest that between 19% and 29% of teachers experienced clinically significant distress at each time-point. CONCLUSIONS: We detected high and sustained levels of psychological distress among primary school teachers, which suggests an urgent need for intervention. Effective support for teachers' mental health is particularly important given the potential impact of poor teacher mental health on pupil well-being, pupil attainment and teacher-pupil relationships.

Positive reinforcement targeting abstinence in substance misuse (PRAISe): Study protocol for a Cluster RCT & process evaluation of contingency management.

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

Refractory depression: mechanisms and evaluation of radically open dialectical behaviour therapy (RO-DBT) [REFRAMED]: protocol for randomised trial.

INTRODUCTION: Only 30-40% of depressed patients treated with medication achieve full remission. Studies that change medication or augment it by psychotherapy achieve only limited benefits, in part because current treatments are not designed for chronic and complex patients. Previous trials have excluded high-risk patients and those with comorbid personality disorder. Radically Open Dialectical Behaviour Therapy (RO-DBT) is a novel, transdiagnostic treatment for disorders of emotional over-control. The REFRAMED trial aims to evaluate the effectiveness and cost-effectiveness of RO-DBT for patients with treatment-resistant depression. METHODS AND ANALYSIS: REFRAMED is a multicentre randomised controlled trial, comparing 7 months of individual and group RO-DBT treatment with treatment as usual (TAU). Our primary outcome measure is depressive symptoms 12 months after randomisation. We shall estimate the cost-effectiveness of RO-DBT by cost per quality-adjusted life year. Causal analyses will explore the mechanisms by which RO-DBT is effective. ETHICS AND DISSEMINATION: The National Research Ethics Service (NRES) Committee South Central - Southampton A first granted ethical approval on 20 June 2011, reference number 11/SC/0146. TRIAL REGISTRATION NUMBER: ISRCTN85784627.

The state of the art in European research on reducing social exclusion and stigma related to mental health: a systematic mapping of the literature.

Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe-primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.

Linking abuse and recovery through advocacy: an observational study.

Aims. High numbers of psychiatric service users experience domestic violence, yet limited interventions exist for these victims. We piloted a domestic violence intervention for community mental health services to explore the feasibility of a future cluster randomized controlled trial. Methods. Quasi-experimental controlled design within five Community Mental Health Teams (three intervention and two control teams). The intervention comprised domestic violence training for clinicians' and referral to domestic violence advocacy for service users. Clinicians' (n = 29) domestic violence knowledge, attitudes and behaviours were assessed before and 6 months post-training. Service users' (n = 34) safety behaviours, unmet needs, quality of life and frequency/severity of abuse were examined at baseline and 3 months follow-up. Process evaluation data were also collected. Results. Clinicians receiving the intervention reported significant improvements in domestic violence knowledge, attitudes and behaviours at follow-up (p < 0.05). Service users receiving the intervention reported significant reductions in violence (p < 0.001) and unmet needs at follow-up (p < 0.05). Conclusions. Interventions comprising domestic violence training for clinicians and referral to domestic violence advocacy may improve responses of psychiatric services. Low rates of identification among teams not receiving training suggest that future trials using service user outcomes are unlikely to be feasible. Therefore, other methods of evaluation are needed.

Group art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).

OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia. DESIGN: A three-arm, parallel group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by study centre. SETTING: Study participants were recruited from secondary care mental health and social services in four UK centres. PARTICIPANTS: Potential participants were aged 18 years or over, had a clinical diagnosis of schizophrenia, confirmed by an examination of case notes, and provided written informed consent. We excluded those who were unable to speak sufficient English to complete the baseline assessment, those with severe cognitive impairment and those already receiving arts therapy. INTERVENTIONS: Group art therapy was delivered by registered art therapists according to nationally agreed standards. Groups had up to eight members, lasted for 90 minutes and ran for 12 months. Members were given access to a range of art materials and encouraged to use these to express themselves freely. Activity groups were designed to control for the non-specific effects of group art therapy. Group facilitators offered various activities and encouraged participants to collectively select those they wanted to pursue. Standard care involved follow-up from secondary care mental health services and the option of referral to other services, except arts therapies, as required. MAIN OUTCOME MEASURES: Our co-primary outcomes were global functioning (measured using the Global Assessment of Functioning Scale - GAF) and mental health symptoms (measured using the Positive and Negative Syndrome Scale - PANSS) at 24 months. The main secondary outcomes were level of group attendance, social functioning, well-being, health-related quality of life, service utilisation and other costs measured 12 and 24 months after randomisation. RESULTS: Four hundred and seventeen people were recruited, of whom 355 (85%) were followed up at 2 years. Eighty-six (61%) of those randomised to art therapy and 73 (52%) of those randomised to activity groups attended at least one group. No differences in primary outcomes were found between the three study arms. The adjusted mean difference between art therapy and standard care at 24 months was -0.9 [95% confidence interval (CI) -3.8 to 2.1] on the GAF Scale and 0.7 (95% CI -3.1 to 4.6) on the PANSS Scale. Differences in secondary outcomes were not found, except that those referred to an activity group had fewer positive symptoms of schizophrenia at 24 months than those randomised to art therapy. Secondary analysis indicated that attendance at art therapy groups was not associated with improvements in global functioning or mental health. Although the total cost of the art therapy group was lower than the cost of the two comparison groups, referral to group art therapy did not appear to provide a cost-effective use of resources. CONCLUSIONS: Referring people with established schizophrenia to group art therapy as delivered in this randomised trial does not appear to improve global functioning or mental health of patients or provide a more cost-effective use of resources than standard care alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 46150447. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 8. See the HTA programme website for further project information.

Group therapy for adolescents with repeated self harm: randomised controlled trial with economic evaluation.

OBJECTIVE: To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people. DESIGN: Two arm, single (assessor) blinded parallel randomised allocation trial of a group therapy intervention in addition to routine care, compared with routine care alone. Randomisation was by minimisation controlling for baseline frequency of self harm, presence of conduct disorder, depressive disorder, and severity of psychosocial stress. PARTICIPANTS: Adolescents aged 12-17 years with at least two past episodes of self harm within the previous 12 months. Exclusion criteria were: not speaking English, low weight anorexia nervosa, acute psychosis, substantial learning difficulties (defined by need for specialist school), current containment in secure care. Setting Eight child and adolescent mental health services in the northwest UK. INTERVENTIONS: Manual based developmental group therapy programme specifically designed for adolescents who harm themselves, with an acute phase over six weekly sessions followed by a booster phase of weekly groups as long as needed. Details of routine care were gathered from participating centres. MAIN OUTCOME MEASURES: Primary outcome was frequency of subsequent repeated episodes of self harm. Secondary outcomes were severity of subsequent self harm, mood disorder, suicidal ideation, and global functioning. Total costs of health, social care, education, and criminal justice sector services, plus family related costs and productivity losses, were recorded. RESULTS: 183 adolescents were allocated to each arm (total n = 366). Loss to follow-up was low (<4%). On all outcomes the trial cohort as a whole showed significant improvement from baseline to follow-up. On the primary outcome of frequency of self harm, proportional odds ratio of group therapy versus routine care adjusting for relevant baseline variables was 0.99 (95% confidence interval 0.68 to 1.44, P = 0.95) at 6 months and 0.88 (0.59 to 1.33, P = 0.52) at 1 year. For severity of subsequent self harm the equivalent odds ratios were 0.81 (0.54 to 1.20, P = 0.29) at 6 months and 0.94 (0.63 to 1.40, P = 0.75) at 1 year. Total 1 year costs were higher in the group therapy arm (£21,781) than for routine care (£15,372) but the difference was not significant (95% CI -1416 to 10782, P = 0.132). CONCLUSIONS: The addition of this targeted group therapy programme did not improve self harm outcomes for adolescents who repeatedly self harmed, nor was there evidence of cost effectiveness. The outcomes to end point for the cohort as a whole were better than current clinical expectations. Trial registration ISRCTN 20496110.

Alternatives to standard acute in-patient care in England: short-term clinical outcomes and cost-effectiveness.

BACKGROUND: Outcomes following admission to residential alternatives to standard in-patient mental health services are underresearched. AIMS: To explore short-term outcomes and costs of admission to alternative and standard services. METHOD: Health of the Nation Outcome Scales (HoNOS), Threshold Assessment Grid (TAG), Global Assessment of Functioning (GAF) and admission cost data were collected for six alternative services and six standard services. RESULTS: All outcomes improved during admission for both types of service (n = 433). Adjusted improvement was greater for standard services in scores on HoNOS (difference 1.99, 95% CI 1.12-2.86), TAG (difference 1.40, 95% CI 0.39-2.51) and GAF functioning (difference 4.15, 95% CI 1.08-7.22) but not GAF symptoms. Admissions to alternatives were 20.6 days shorter, and hence cheaper (UK pound3832 v. pound9850). Standard services cost an additional pound2939 per unit HoNOS improvement. CONCLUSIONS: The absence of clear-cut advantage for either type of service highlights the importance of the subjective experience and longer-term costs.

Effectiveness and cost-effectiveness of admissions to women's crisis houses compared with traditional psychiatric wards: pilot patient-preference randomised controlled trial.

BACKGROUND: Women's crisis houses have been developed in the UK as a less stigmatising and less institutional alternative to traditional psychiatric wards. AIMS: To examine the effectiveness and cost-effectiveness of women's crisis houses by first examining the feasibility of a pilot patient-preference randomised controlled trial (PP-RCT) design (ISRCTN20804014). METHOD: We used a PP-RCT study design to investigate women presenting in crisis needing informal admission. The four study arms were the patient preference arms of women's crisis house or hospital admission, and randomised arms of women's crisis house or hospital admission. RESULTS: Forty-one women entered the randomised arms of the trial (crisis house n = 19, wards n = 22) and 61 entered the patient-preference arms (crisis house n = 37, ward n = 24). There was no significant difference in outcomes (symptoms, functioning, perceived coercion, stigma, unmet needs or quality of life) or costs for any of the groups (randomised or preference arms), but women who obtained their preferred intervention were more satisfied with treatment. CONCLUSIONS: Although the sample sizes were too small to allow definite conclusions, the results suggest that when services are able to provide interventions preferred by patients, those patients are more likely to be satisfied with treatment. This pilot study provides some evidence that women's crisis houses are as effective as traditional psychiatric wards, and may be more cost-effective.

Alternatives to standard acute in-patient care in England: roles and populations served.

BACKGROUND: Key questions regarding residential alternatives to standard acute psychiatric care, such as crisis houses and short-stay in-patient units, concern the role that they fulfil within local acute care systems, and whether they manage people with needs and illnesses of comparable severity to those admitted to standard acute wards. AIMS: To study the extent to which people admitted to residential alternatives and to standard acute services are similar, and the role within local acute care systems of admission to an alternative service. METHOD: Our approach combined quantitative and qualitative methods. Consecutive cohorts of patients in six residential alternatives across England and six standard acute wards in the same areas were identified, and clinical and demographic characteristics, severity of symptoms, impairments and risks compared. Semi-structured interviews with key stakeholders in each local service system were used to explore the role and functioning of each alternative. RESULTS: Being already known to services (OR = 2.6, 95% CI 1.3-5.2), posing a lower risk to others (OR = 0.49, 95% CI 0.31-0.78) and having initiated help-seeking in the current crisis (OR = 2.2, 95% CI 1.2-4.3) were associated with being admitted to an alternative rather than a standard service. Stakeholder interviews suggested that alternatives have a role that is similar but not identical to standard hospital services. They can divert some, but not all, patients from acute admission. CONCLUSIONS: Residential alternatives are integrated into catchment area mental health systems. They serve similar, but not identical, clinical populations to standard acute wards and provide some, but not all, of the functions of these wards.

A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability - the TOuCAN trial.

OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of inpatient compared with outpatient treatment and general (routine) treatment in Child and Adolescent Mental Health Services (CAMHS) against specialist treatment for young people with anorexia nervosa. In addition, to determine young people's and their carers' satisfaction with these treatments. DESIGN: A population-based, pragmatic randomised controlled trial (RCT) was carried out on young people age 12 to 18 presenting to community CAMHS with anorexia nervosa. SETTING: Thirty-five English CAMHS in the north-west of England co-ordinated through specialist centres in Manchester and Liverpool. PARTICIPANTS: Two hundred and fifteen young people (199 female) were identified, of whom 167 (mean age 14 years 11 months) were randomised and 48 were followed up as a preference group. INTERVENTIONS: Randomised patients were allocated to either inpatient treatment in one of four units with considerable experience in the treatment of anorexia nervosa, a specialist outpatient programme delivered in one of two centres, or treatment as usual in general community CAMHS. The outpatient programmes spanned 6 months of treatment. The length of inpatient treatment was determined on a case-by-case basis on clinical need with outpatient follow-up to a minimum of 6 months. MAIN OUTCOME MEASURES: Follow-up assessments were carried out at 1, 2 and 5 years. The primary outcome measure was the Morgan-Russell Average Outcome Scale (MRAOS) and associated categorical outcomes. Secondary outcome measures included physical measures of weight, height, body mass index (BMI) and % weight for height. Research ratings included the Health of the National Outcome Scale for Children and Adolescents (HoNOSCA). Self report measures comprised the user version of HoNOSCA (HoNOSCA-SR), the Eating Disorder Inventory 2 (EDI-2), the Family Assessment Device (FAD) and the recent Mood and Feelings Questionnaire (MFQ). Information on resource use was collected in interview at 1, 2 and 5 years using the Child and Adolescent Service Use Schedule (CA-SUS). Satisfaction was measured quantitatively using a questionnaire designed for the study and qualitative (free) responses on it. The questionnaire data were supplemented by qualitative analysis of user and carer focus groups. RESULTS: Of the 167 patients randomised, 65% adhered to the allocated treatment. Adherence was lower for inpatient treatment (49%) than for general CAMHS (71%) or specialist outpatient treatment (77%) (p = 0.013). Every subject was traced at both 1 and 2 years, with the main outcome measure completed (through contact with the subject, family members or clinicians), by 94% at 1 year, 93% at 2 years, but only 47% at 5 years. A validated outcome category was assigned for 98% at 1 year, 96% at 2 years and 60% at 5 years. There was significant improvement in all groups at each time point, with the number achieving a good outcome being 19% at 1 year, 33% at 2 years and 64% (of those followed up) at 5 years. Analysis demonstrated no difference in treatment effectiveness of randomisation to inpatient compared with outpatient treatment, or, specialist over generalist treatment at any time point, when baseline characteristics were taken into account. Generalist CAMHS treatment was slightly more expensive over the first 2 years of the study, largely because greater numbers were subsequently admitted to hospital after the initial treatment phase. The specialist outpatient programme was the dominant treatment in terms of incremental cost-effectiveness. Specialist treatments had a higher probability of being more cost-effective than generalist treatments and outpatient treatment had a higher probability of being more cost-effective than inpatient care. Parental satisfaction with treatment was generally good, though better with specialist than generalist treatment. Young people's satisfaction was much more mixed, but again better with specialist treatment, including inpatient care. CONCLUSION: Poor adherence to randomisation (despite initial consent to it), limits the assessment of the treatment effect of inpatient care. However, this study provides little support for lengthy inpatient psychiatric treatment on clinical or health economic grounds. These findings are broadly consistent with existing guidelines on the treatment of anorexia nervosa, which suggest that outpatient treatments should be offered to the majority, with inpatient treatment offered in rare cases, though our findings lend little support to a stepped-care approach in which inpatient care is offered to outpatient non-responders. Outpatient care, supported by brief (medical) inpatient management for correction of acute complications may be a preferable approach. The health economic analysis and user views both support NICE guidelines, which suggest that anorexia nervosa should be managed in specialist services that have experience and expertise in its management. Comprehensive general CAMHS might, however, be well placed to manage milder cases. Further research should focus on the specific components of outpatient psychological therapies. Although family-based treatments are well established, trials have not established their effectiveness compared with good-quality individual psychological therapies and the combination of individual and family approaches is untested. Further research is needed to establish which patients (if any) might respond to inpatient psychiatric treatment when unresponsive to outpatient care, the positive and negative components of it and the optimum length of stay. TRIAL REGISTRATION: NRR number (National Research Register) N0484056615; Current Controlled Trials ISRCTN39345394.

A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial.

OBJECTIVES: To determine if, in the short term, depressed adolescents attending routine NHS Child and Adolescent Mental Health Services (CAMHS), and receiving ongoing active clinical care, treatment with selective serotonin reuptake inhibitors (SSRIs) plus cognitive behaviour therapy (CBT) compared with SSRI alone, results in better healthcare outcomes. DESIGN: A pragmatic randomised controlled trial (RCT) was conducted on depressed adolescents attending CAMHS who had not responded to a psychosocial brief initial intervention (BII) prior to randomisation. SETTING: Six English CAMHS participated in the study. PARTICIPANTS: A total of 208 patients aged between 11 and 17 years were recruited and randomised. INTERVENTIONS: All participants received active routine clinical care in a CAMHS outpatient setting and an SSRI and half were offered CBT. MAIN OUTCOME MEASURES: The duration of the trial was a 12-week treatment phase, followed by a 16-week maintenance phase. Follow-up assessments were at 6, 12 and 28 weeks. The primary outcome measure was the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). Secondary outcome measures were self-report depressive symptoms, interviewer-rated depressive signs and symptoms, interviewer-rated psychosocial impairment and clinical global impression of response to treatment. Information on resource use was collected in interview at baseline and at the 12- and 28-week follow-up assessments using the Child and Adolescent Service Use Schedule (CA-SUS). RESULTS: Of the 208 patients randomised, 200 (96%) completed the trial to the primary end-point at 12 weeks. By the 28-week follow-up, 174 (84%) participants were re-evaluated. Overall, 193 (93%) participants had been assessed at one or more time points. Clinical characteristics indicated that the trial was conducted on a severely depressed group. There was significant recovery at all time points in both arms. The findings demonstrated no difference in treatment effectiveness for SSRI + CBT over SSRI only for the primary or secondary outcome measures at any time point. This lack of difference held when baseline and treatment characteristics where taken into account (age, sex, severity, co-morbid characteristics, quality and quantity of CBT treatment, number of clinic attendances). The SSRI + CBT group was somewhat more expensive over the 28 weeks than the SSRI-only group (p=0.057) and no more cost-effective. Over the trial period there was on average a decrease in suicidal thoughts and self-harm compared with levels recorded at baseline. There was no significant increase in disinhibition, irritability and violence compared with levels at baseline. Around 20% (n=40) of patients in the trial were non-responders. Of these, 17 (43%) showed no improvement by 28 weeks and 23 (57%) were considered minimally (n=10) or moderately to severely worse (n=13). CONCLUSIONS: For moderately to severely depressed adolescents who are non-responsive to a BII, the addition of CBT to fluoxetine plus routine clinical care does not improve outcome or confer protective effects against adverse events and is not cost-effective. SSRIs (mostly fluoxetine) are not likely to result in harmful adverse effects. The findings are broadly consistent with existing guidelines on the treatment of moderate to severe depression. Modification is advised for those presenting with moderate (6-8 symptoms) to severe depressions (>8 symptoms) and in those with either overt suicidal risk and/or high levels of personal impairment. In such cases, the time allowed for response to psychosocial interventions should be no more than 2-4 weeks, after which fluoxetine should be prescribed. Further research should focus on evaluating the efficacy of specific psychological treatments against brief psychological intervention, determining the characteristics of patients with severe depression who are non-responsive to fluoxetine, relapse prevention in severe depression and improving tools for determining treatment responders and non-responders.

Cost-effectiveness of selective serotonin reuptake inhibitors and routine specialist care with and without cognitive behavioural therapy in adolescents with major depression.

BACKGROUND: Major depression is an important and costly problem among adolescents, yet evidence to support the provision of cost-effective treatments is lacking. AIMS: To assess the short-term cost-effectiveness of combined selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) together with clinical care compared with SSRIs and clinical care alone in adolescents with major depression. METHOD: Pragmatic randomised controlled trial in the UK. Outcomes and costs were assessed at baseline, 12 and 28 weeks. RESULTS: The trial comprised 208 adolescents, aged 11-17 years, with major or probable major depression who had not responded to a brief initial psychosocial intervention. There were no significant differences in outcome between the groups with and without CBT. Costs were higher in the group with CBT, although not significantly so (P=0.057). Cost-effectiveness analysis and exploration of the associated uncertainty suggest there is less than a 30% probability that CBT plus SSRIs is more cost-effective than SSRIs alone. CONCLUSIONS: A combination of CBT plus SSRIs is not more cost-effective in the short-term than SSRIs alone for treating adolescents with major depression in receipt of routine specialist clinical care.

Do care patterns change over time in a newly established mental health service? A report from the UK700 trial.

PURPOSE: Data on the process of mental health care is scant. Most studies focus on services at their inception when activity may be atypical and then usually present data only mean values for the reported variables over the whole study period. We aimed to test whether care delivery changes over time, and to describe any changes at the individual patient and team levels. METHODS: Process data on 272 patients in three new intensive case management (ICM) teams were collected over 2 years. Interventions were prospectively recorded using clinician-derived categories. Changes over time are described at both patient and team level. RESULTS: The number of contacts and the proportion of face-to-face activity were remarkably constant after the first month at the patient level. The proportion of 'psychiatric' interventions (main focus on medication or a specific 'mental health' intervention performed) increased greatly after the first 6 months. The care activity received by individual patients varied considerably. Overall, teams varied significantly in the extent to which their activity rates were sustained over time. CONCLUSIONS: New ICM teams deliver highly individualised care with more marked differences in treatment patterns between patients in the same team than mean differences between teams. The early 'engagement' period is marked by a greater focus on social care. There is evidence of differences in sustainability of the services by site.

The Nottingham study of neurotic disorder: predictors of 12 year costs.

OBJECTIVE: To examine the relationship between clinical, demographic and socio-economic characteristics and the long-term costs of a cohort of neurotic patients. METHOD: Analysis of the costs of a cohort of 210 people entered in the Nottingham study of neurotic disorders, a randomized controlled evaluation of five treatments for neurotic disorders. Service use data were collected at 5 and 12 years after study entry. Multiple regression analyses were conducted. RESULTS: The total cost per patient over the 12-year follow-up period was calculated to be $11,940 (SD $15,520) ( pound7450, SD pound9690). Higher costs were significantly associated with the presence of general neurotic syndrome, an initial diagnosis of dysthymia and a recurrent episode of illness. CONCLUSION: The total costs of care for a range of neurotic disorders are broadly comparable with other estimates of costs reported in the literature for similar populations. Those responsible for higher costs in the longer-term have comorbid anxiety, depressive and personality disorders.

Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study.

BACKGROUND: We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD: Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months. RESULTS: Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20). CONCLUSION: Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.