The development and internal evaluation of a predictive model to identify for whom Mindfulness-Based Cognitive Therapy (MBCT) offers superior relapse prevention for recurrent depression versus maintenance antidepressant medication.

Depression is highly recurrent, even following successful pharmacological and/or psychological intervention. We aimed to develop clinical prediction models to inform adults with recurrent depression choosing between antidepressant medication (ADM) maintenance or switching to Mindfulness-Based Cognitive Therapy (MBCT). Using data from the PREVENT trial (N=424), we constructed prognostic models using elastic net regression that combined demographic, clinical and psychological factors to predict relapse at 24 months under ADM or MBCT. Only the ADM model (discrimination performance: AUC=.68) predicted relapse better than baseline depression severity (AUC=.54; one-tailed DeLong's test: z=2.8, p=.003). Individuals with the poorest ADM prognoses who switched to MBCT had better outcomes compared to those who maintained ADM (48% vs. 70% relapse, respectively; superior survival times [z=-2.7, p=.008]). For individuals with moderate-to-good ADM prognosis, both treatments resulted in similar likelihood of relapse. If replicated, the results suggest that predictive modeling can inform clinical decision-making around relapse prevention in recurrent depression.

Pharmacological interventions for treatment-resistant depression in adults.

BACKGROUND: Although antidepressants are often a first-line treatment for adults with moderate to severe depression, many people do not respond adequately to medication, and are said to have treatment-resistant depression (TRD). Little evidence exists to inform the most appropriate 'next step' treatment for these people. OBJECTIVES: To assess the effectiveness of standard pharmacological treatments for adults with TRD. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (March 2016), CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science (31 December 2018), the World Health Organization trials portal and ClinicalTrials.gov for unpublished and ongoing studies, and screened bibliographies of included studies and relevant systematic reviews without date or language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) with participants aged 18 to 74 years with unipolar depression (based on criteria from DSM-IV-TR or earlier versions, International Classification of Diseases (ICD)-10, Feighner criteria or Research Diagnostic Criteria) who had not responded to a minimum of four weeks of antidepressant treatment at a recommended dose. Interventions were: (1) increasing the dose of antidepressant monotherapy; (2) switching to a different antidepressant monotherapy; (3) augmenting treatment with another antidepressant; (4) augmenting treatment with a non-antidepressant. All were compared with continuing antidepressant monotherapy. We excluded studies of non-standard pharmacological treatments (e.g. sex hormones, vitamins, herbal medicines and food supplements). DATA COLLECTION AND ANALYSIS: Two reviewers used standard Cochrane methods to extract data, assess risk of bias, and resolve disagreements. We analysed continuous outcomes with mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (CI). For dichotomous outcomes, we calculated a relative risk (RR) and 95% CI. Where sufficient data existed, we conducted meta-analyses using random-effects models. MAIN RESULTS: We included 10 RCTs (2731 participants). Nine were conducted in outpatient settings and one in both in- and outpatients. Mean age of participants ranged from 42 - 50.2 years, and most were female. One study investigated switching to, or augmenting current antidepressant treatment with, another antidepressant (mianserin). Another augmented current antidepressant treatment with the antidepressant mirtazapine. Eight studies augmented current antidepressant treatment with a non-antidepressant (either an anxiolytic (buspirone) or an antipsychotic (cariprazine; olanzapine; quetiapine (3 studies); or ziprasidone (2 studies)). We judged most studies to be at a low or unclear risk of bias. Only one of the included studies was not industry-sponsored. There was no evidence of a difference in depression severity when current treatment was switched to mianserin (MD on Hamilton Rating Scale for Depression (HAM-D) = -1.8, 95% CI -5.22 to 1.62, low-quality evidence)) compared with continuing on antidepressant monotherapy. Nor was there evidence of a difference in numbers dropping out of treatment (RR 2.08, 95% CI 0.94 to 4.59, low-quality evidence; dropouts 38% in the mianserin switch group; 18% in the control). Augmenting current antidepressant treatment with mianserin was associated with an improvement in depression symptoms severity scores from baseline (MD on HAM-D -4.8, 95% CI -8.18 to -1.42; moderate-quality evidence). There was no evidence of a difference in numbers dropping out (RR 1.02, 95% CI 0.38 to 2.72; low-quality evidence; 19% dropouts in the mianserin-augmented group; 38% in the control). When current antidepressant treatment was augmented with mirtazapine, there was little difference in depressive symptoms (MD on Beck Depression Inventory (BDI-II) -1.7, 95% CI -4.03 to 0.63; high-quality evidence) and no evidence of a difference in dropout numbers (RR 0.50, 95% CI 0.15 to 1.62; dropouts 2% in mirtazapine-augmented group; 3% in the control). Augmentation with buspirone provided no evidence of a benefit in terms of a reduction in depressive symptoms (MD on Montgomery and Asberg Depression Rating Scale (MADRS) -0.30, 95% CI -9.48 to 8.88; low-quality evidence) or numbers of drop-outs (RR 0.60, 95% CI 0.23 to 1.53; low-quality evidence; dropouts 11% in buspirone-augmented group; 19% in the control). Severity of depressive symptoms reduced when current treatment was augmented with cariprazine (MD on MADRS -1.50, 95% CI -2.74 to -0.25; high-quality evidence), olanzapine (MD on HAM-D -7.9, 95% CI -16.76 to 0.96; low-quality evidence; MD on MADRS -12.4, 95% CI -22.44 to -2.36; low-quality evidence), quetiapine (SMD -0.32, 95% CI -0.46 to -0.18; I2 = 6%, high-quality evidence), or ziprasidone (MD on HAM-D -2.73, 95% CI -4.53 to -0.93; I2 = 0, moderate-quality evidence) compared with continuing on antidepressant monotherapy. However, a greater number of participants dropped out when antidepressant monotherapy was augmented with an antipsychotic (cariprazine RR 1.68, 95% CI 1.16 to 2.41; quetiapine RR 1.57, 95% CI: 1.14 to 2.17; ziprasidone RR 1.60, 95% CI 1.01 to 2.55) compared with antidepressant monotherapy, although estimates for olanzapine augmentation were imprecise (RR 0.33, 95% CI 0.04 to 2.69). Dropout rates ranged from 10% to 39% in the groups augmented with an antipsychotic, and from 12% to 23% in the comparison groups. The most common reasons for dropping out were side effects or adverse events. We also summarised data about response and remission rates (based on changes in depressive symptoms) for included studies, along with data on social adjustment and social functioning, quality of life, economic outcomes and adverse events. AUTHORS' CONCLUSIONS: A small body of evidence shows that augmenting current antidepressant therapy with mianserin or with an antipsychotic (cariprazine, olanzapine, quetiapine or ziprasidone) improves depressive symptoms over the short-term (8 to 12 weeks). However, this evidence is mostly of low or moderate quality due to imprecision of the estimates of effects. Improvements with antipsychotics need to be balanced against the increased likelihood of dropping out of treatment or experiencing an adverse event. Augmentation of current antidepressant therapy with a second antidepressant, mirtazapine, does not produce a clinically important benefit in reduction of depressive symptoms (high-quality evidence). The evidence regarding the effects of augmenting current antidepressant therapy with buspirone or switching current antidepressant treatment to mianserin is currently insufficient. Further trials are needed to increase the certainty of these findings and to examine long-term effects of treatment, as well as the effectiveness of other pharmacological treatment strategies.

Effectiveness of an integrated telehealth service for patients with depression: a pragmatic randomised controlled trial of a complex intervention.

BACKGROUND: Many countries are exploring the potential of telehealth interventions to manage the rising number of people with chronic disorders. However, evidence of the effectiveness of telehealth is ambiguous. Based on an evidence-based conceptual framework, we developed an integrated telehealth service (the Healthlines Service) for chronic disorders and assessed its effectiveness in patients with depression. We aimed to compare the Healthlines Depression Service plus usual care with usual care alone. METHODS: This study was a pragmatic, multicentre, randomised controlled trial with participants recruited from 43 general practices in three areas of England. To be eligible, participants needed to have access to the internet and email, a Patient Health Questionnaire 9 (PHQ-9) score of at least 10, and a confirmed diagnosis of depression. Participants were individually assigned (1:1) to either the Healthlines Depression Service plus usual care or usual care alone. Random assignment was done by use of a web-based automated randomisation system, stratified by site and minimised by practice and PHQ-9 score. Participants were aware of their allocation, but outcomes were analysed masked. The Healthlines Service consisted of regular telephone calls from non-clinical, trained health advisers who followed standardised scripts generated by interactive software. After an initial assessment and goal-setting telephone call, the advisers called each participant on six occasions over 4 months, and then made up to three more calls at intervals of roughly 2 months to provide reinforcement and to detect relapse. Advisers supported participants in the use of online resources (including computerised cognitive behavioural therapy) and sought to encourage healthier lifestyles, optimise medication, and improve treatment adherence. The primary outcome was the proportion of participants responding to the intervention (defined as PHQ-9 <10 and reduction in PHQ-9 of ≥5 points) at 4 months after randomisation. The primary analysis was based on the intention-to-treat principle without imputation and all serious adverse events were investigated. This trial is registered with Current Controlled Trials, number ISRCTN 14172341. FINDINGS: Between July 24, 2012, and July 31, 2013, we recruited 609 participants, randomly assigning 307 to the Healthlines Service plus usual care and 302 to usual care. Primary outcome data were available for 525 (86%) participants. At 4 months, 68 (27%) of 255 individuals in the intervention group had a treatment response compared with 50 (19%) of 270 individuals in the usual care group (adjusted odds ratio 1·7, 95% CI 1·1-2·5, p=0·019). Compared with usual care alone, intervention participants reported improvements in anxiety, better access to support and advice, greater satisfaction with the support they received, and improvements in self-management and health literacy. During the trial, 70 adverse events were reported by participants, one of which was related to the intervention (increased anxiety from discussing depression) and was not serious. INTERPRETATION: This telehealth service based on non-clinically trained health advisers supporting patients in use of internet resources was both acceptable and effective compared with usual care. Our results provide support for the development and assessment of similar interventions in other chronic disorders to expand care provision. FUNDING: National Institute for Health Research (NIHR).

The effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse/recurrence: results of a randomised controlled trial (the PREVENT study).

BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse/recurrence. Maintenance antidepressant medication (m-ADM) for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to m-ADM. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce the risk of relapse/recurrence compared with usual care but has not yet been compared with m-ADM in a definitive trial. OBJECTIVES: To establish whether MBCT with support to taper and/or discontinue antidepressant medication (MBCT-TS) is superior to and more cost-effective than an approach of m-ADM in a primary care setting for patients with a history of recurrent depression followed up over a 2-year period in terms of preventing depressive relapse/recurrence. Secondary aims examined MBCT's acceptability and mechanism of action. DESIGN: Single-blind, parallel, individual randomised controlled trial. SETTING: UK general practices. PARTICIPANTS: Adult patients with a diagnosis of recurrent depression and who were taking m-ADM. INTERVENTIONS: Participants were randomised to MBCT-TS or m-ADM with stratification by centre and symptomatic status. Outcome data were collected blind to treatment allocation and the primary analysis was based on the principle of intention to treat. Process studies using quantitative and qualitative methods examined MBCT's acceptability and mechanism of action. MAIN OUTCOMES MEASURES: The primary outcome measure was time to relapse/recurrence of depression. At each follow-up the following secondary outcomes were recorded: number of depression-free days, residual depressive symptoms, quality of life, health-related quality of life and psychiatric and medical comorbidities. RESULTS: In total, 212 patients were randomised to MBCT-TS and 212 to m-ADM. The primary analysis did not find any evidence that MBCT-TS was superior to m-ADM in terms of the primary outcome of time to depressive relapse/recurrence over 24 months [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.67 to 1.18] or for any of the secondary outcomes. Cost-effectiveness analysis did not support the hypothesis that MBCT-TS is more cost-effective than m-ADM in terms of either relapse/recurrence or quality-adjusted life-years. In planned subgroup analyses, a significant interaction was found between treatment group and reported childhood abuse (HR 1.89, 95% CI 1.06 to 3.38), with delayed time to relapse/recurrence for MBCT-TS participants with a more abusive childhood compared with those with a less abusive history. Although changes in mindfulness were specific to MBCT (and not m-ADM), they did not predict outcome in terms of relapse/recurrence at 24 months. In terms of acceptability, the qualitative analyses suggest that many people have views about (dis)/continuing their ADM, which can serve as a facilitator or a barrier to taking part in a trial that requires either continuation for 2 years or discontinuation. CONCLUSIONS: There is no support for the hypothesis that MBCT-TS is superior to m-ADM in preventing depressive relapse/recurrence among individuals at risk for depressive relapse/recurrence. Both treatments appear to confer protection against relapse/recurrence. There is an indication that MBCT may be most indicated for individuals at greatest risk of relapse/recurrence. It is important to characterise those most at risk and carefully establish if and why MBCT may be most indicated for this group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN26666654. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula and will be published in full in Health Technology Assessment; Vol. 19, No. 73. See the NIHR Journals Library website for further project information.

Examining reward-seeking, negative self-beliefs and over-general autobiographical memory as mechanisms of change in classroom prevention programs for adolescent depression.

BACKGROUND: Effective methods to prevent adolescent depressive symptoms could reduce suffering and burden across the lifespan. However, psychological interventions delivered to adolescents show efficacy only in symptomatic or high-risk youth. Targeting causal risk factors and assessing mechanistic change can help devise efficacious universal or classroom based prevention programs. METHODS: A non-randomized longitudinal design was used to compare three classroom-based prevention programs for adolescent depression (Behavioral Activation with Reward Processing, "Thinking about Reward in Young People" (TRY); Cognitive Behavioral Therapy (CBT) and Mindfulness Based Cognitive Therapy (MBCT)), and determine cognitive mechanisms of change in these programs. Cognitive mechanisms examined were reward-seeking, negative self-beliefs (assessed with behavioral tasks) and over-general autobiographical memory. 256 healthy adolescents aged 13-14 participated with 236 (92%) and 227 (89%) completing the pre- and post-assessments. RESULTS: TRY was the only intervention associated with a reduction in depressive symptoms at follow-up. Reward-seeking increased following TRY. In the other programs there were non-significant changes in cognitive mechanisms, with more reflective negative self-beliefs in CBT and fewer over-general autobiographical memories in MBCT In the TRY program, which focused on increasing sensitivity to rewarding activities, reward seeking increased and this was associated with decreased depressive symptoms. LIMITATIONS: Due to the infeasibility of a cluster randomized controlled trial, a non-randomized design was used. CONCLUSIONS: Increased reward-seeking was associated with decreased depressive symptoms and may be a mechanism of depressive symptom change in the intervention with a focus on enhancing sensitivity and awareness of reward. This study provides preliminary evidence to suggest that incorporating activities to enhance reward sensitivity may be fruitful in randomized controlled trials of universal prevention programs for depression.

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. METHODS: In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. FINDINGS: Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18; p=0·43), nor did the number of serious adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance antidepressants groups. No adverse events were attributable to the interventions or the trial. INTERPRETATION: We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

Update to the study protocol for a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment depressive relapse/recurrence: the PREVENT trial.

BACKGROUND: Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. A recently developed treatment, mindfulness-based cognitive therapy (MBCT), shows potential as a brief group program for people with recurring depression.This trial asks the policy research question; is MBCT with support to taper/discontinue antidepressant medication (MBCT-TS) superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant medication (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? An explanatory research question also asks whether an increase in mindfulness skills is the key mechanism of change.The design is a single-blind, parallel randomized controlled trial examining MBCT-TS versus m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT-TS with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. RESULTS: Depressive relapse/recurrence over two years is the primary outcome variable. Analyses will be conducted following CONSORT standards and overseen by the trial's Data Monitoring and Safety Committee. Initial analyses will be conducted on an intention-to-treat basis, with subsequent analyses being per protocol. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre- and post-treatment and a qualitative study of service users' views and experiences. CONCLUSIONS: If the results of our exploratory trial are extended to this definitive trial, MBCT-TS will be established as an alternative approach to maintenance antidepressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches. TRIAL REGISTRATION: Trial registered 7 May 2009; ISRCTN26666654.

Effects of emotion perception training on mood in undergraduate students: randomised controlled trial.

We investigated the effects of emotion perception training on depressive symptoms and mood in young adults reporting high levels of depressive symptoms (trial registration: ISRCTN02532638). Participants were randomised to an intervention procedure designed to increase the perception of happiness over sadness in ambiguous facial expressions or a control procedure, and completed self-report measures of depressive symptoms and mood. Those in the intervention condition had lower depressive symptoms and negative mood at 2-week follow-up, but there was no statistical evidence for a difference. There was some evidence for increased positive mood. Modification of emotional perception may lead to an increase in positive affect.

Study protocol for a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment in the prevention of depressive relapse/recurrence: the PREVENT trial.

BACKGROUND: Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. We need to develop psychological therapies that prevent depressive relapse/recurrence. A recently developed treatment, Mindfulness-based Cognitive Therapy (MBCT, see http://www.mbct.co.uk) shows potential as a brief group programme for people with recurring depression. In two studies it has been shown to halve the rates of depression recurring compared to usual care.This trial asks the policy research question, is MBCT superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and, secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? An explanatory research question asks is an increase in mindfulness skills the key mechanism of change? METHODS/DESIGN: The design is a single blind, parallel RCT examining MBCT vs. m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT plus ADM-tapering with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. Depressive relapse/recurrence over two years is the primary outcome variable. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre/post-treatment and a qualitative study of service users' views and experiences. DISCUSSION: If the results of our exploratory trial are extended to this definitive trial, MBCT will be established as an alternative approach to maintenance anti-depressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches. TRIAL REGISTRATION NUMBER: ISRCTN26666654.

Mindfulness-based 'third wave' cognitive and behavioural therapies versus other psychological therapies for depression.

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all third wave CBT approaches compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different third wave CBT approaches (ACT,compassionate mind training, functional analytic psychotherapy, extended behavioural activation and meta-cognitive therapy) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all third wave CBT approaches compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression.

Mindfulness-based 'third wave' cognitive and behavioural therapies versus treatment as usual for depression.

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all third wave CBT approaches compared with treatment as usual/waiting list/attention placebo control conditions for acute depression.To examine the effectiveness and acceptability of different third wave CBT approaches (ACT, compassionate mind training, functional analytic psychotherapy, meta-cognitive therapy, dialectical behaviour therapy, MBCT, extended behavioural activation and meta-cognitive therapy) compared with treatment as usual/waiting list/attention placebo control conditions for acute depression.To examine the effectiveness and acceptability of all third wave CBT approaches compared with different types of comparator (standard care, no treatment, waiting list, attention placebo) for acute depression.

Interpersonal, cognitive analytic and other integrative therapies versus other psychological therapies for depression.

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all integrative therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different integrative therapy models (IPT, CAT, psychodynamic-interpersonal therapy, CBASP, counselling) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all integrative therapies compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, cognitive-behavioural, third wave CBT) for acute depression.