The complexity of treatment-resistant depression: A data-driven approach.

BACKGROUND: Recent systematic reviews highlight great variability in defining and assessing treatment-resistant depression (TRD). A key problem is that definitions are consensus rather than data-led. This study seeks to offer a comprehensive socio-demographic and clinical description of a relevant sample. METHODS: As part of a pragmatic randomized controlled trial, patients (N = 129) were managed in primary care for persistent depression and diagnosed with TRD. Data included previous treatment attempts, characteristics of the depressive illness, functioning, quality of life, co-occurring problems including suicidality, psychiatric and personality disorders, physical health conditions, and adverse events. RESULTS: Findings show a severe and chronic course of depression with a duration of illness of 25+ years. Overall, 82.9 % had at least one other psychiatric diagnosis and 82.2 % at least one personality disorder; 69.8 % had significant musculoskeletal, gastrointestinal, genitourinary, or cardiovascular and respiratory physical health problems. All but 14 had severe difficulties in social and occupational functioning and reported severely impaired quality of life. Suicidal ideation was high: 44.9 % had made at least one serious suicide attempt and several reported multiple attempts with 17.8 % reporting a suicide attempt during childhood or adolescence. Of the patients, 79.8 % reported at least one adverse childhood experience. LIMITATIONS: Potential for recall bias, not examining possible interactions, and absence of a control group. CONCLUSIONS: Our findings reveal a complex and multifaceted condition and call for an urgent reconceptualization of TRD, which encompasses many interdependent variables and experiences. Individuals with TRD may be at a serious disadvantage in terms of receiving adequate treatment.

Efficacy of high-intensity versus low-intensity psychoanalytically oriented long-term treatments and determinants of outcome: individual participant data Meta-analysis of Long-term Analytic treatment Studies (MeLAS).

INTRODUCTION: Long-term psychodynamic/psychoanalytic psychotherapy (LTPP) is a prevalent treatment option for complex mental disorders. Yet, little is known about the role of treatment intensity in LTPP. We present a study protocol for a systematic review and individual participant data (IPD) meta-analysis aggregating and analysing individual data from randomised and quasi-experimental trials by meta-analysis. The purpose is to (1) determine the treatment effectiveness of LTPP with low versus high intensity (up to 2 weekly sessions vs three or more), (2) compare their joint effectiveness to shorter therapies and treatments as usual, (3) identify predictors and moderators of treatment outcomes and (4) determine reciprocal relationships between different outcome domains (symptomatic and structural/personality change) over the courses of LTPP. METHODS AND ANALYSIS: We include studies from (randomised controlled trial, RCT) and quasi-experimental trials, where at least one condition was LTPP of high or low frequency. Long-term treatment is defined as ≥1 year or ≥50 sessions. To be eligible studies must include a standardised outcome measure of symptoms (global or disorder specific) with at least one proof of reliability. The primary outcome is symptom reduction (global or specific), secondary outcome criteria are reliable change, remission, functional capacities, personality, personality functioning and interpersonal pathology. Relevant studies will mainly be identified by searching relevant databases: PubMed, PsycINFO (via EBSCO), Web of Science (via Elsevier), Chochrane's Central Register of Controlled Trials (via Wiley). Risk of bias will be evaluated in line with the Cochrane assessments tools for quasi-experimental trials and RCTs, respectively. ETHICS AND DISSEMINATION: Aggregation of data from primary trials collected based on ethics votes. Dissemination into clinical practice via open access publications of findings. PROSPERO REGISTRATION NUMBER: CRD42022304982; Pre-results.

Cost-effectiveness of long-term psychoanalytic psychotherapy for treatment-resistant depression: RCT evidence from the Tavistock Adult Depression Study (TADS).

BACKGROUND: Treatment-resistant depression (TRD) accounts for a large fraction of the burden of depression. The interventions currently used are mostly pharmacological and short-term psychotherapies, but their effectiveness is limited. The Tavistock Adult Depression Study found evidence for the effectiveness of long-term psychoanalytic psychotherapy (LTPP) plus treatment as usual (TAU), versus TAU alone, for TRD. Even after a 2-year follow-up, moderate effect sizes were sustained. This study assessed the cost-effectiveness of this LTPP + TAU. METHODS: We conducted a within-trial economic evaluation using a Bayesian framework. RESULTS: Quality-adjusted life years (QALYs) were 0.16 higher in the LTPP + TAU group compared with TAU. The direct cost of LTPP was £5500, with no substantial compensating savings elsewhere. Overall, average health and social care costs in the LTPP + TAU group were £5000 more than in the TAU group, employment rates were unchanged, and effects on other non-healthcare costs were uncertain. Accordingly, the incremental cost-effectiveness ratio was ≈£33,000/QALY; the probability that LTPP + TAU was cost-effective at a willingness to pay of £20,000/QALY was 18 %. LIMITATIONS: The sample size of this study was relatively small, and the fraction of missing service-use data was approximately 50 % at all time points. The study was conducted at a single site, potentially reducing generalizability. CONCLUSIONS: Although LTPP + TAU was found to be clinically effective for treating TRD, it was not found to be cost-effective compared with TAU. However, given the sustained effects over the follow-up period it is likely that the time horizon of this study was too short to capture all benefits of LTPP augmentation.

Psychotherapy Dropout: Using the Adolescent Psychotherapy Q-Set to Explore the Early In-Session Process of Short-Term Psychodynamic Psychotherapy.

Research suggests that short-term psychodynamic psychotherapy (STPP) is an effective treatment for depression in adolescence, yet treatment dropout is a major concern and what leads to dropout is poorly understood. Whilst studies have begun to explore the role of patient and therapist variables, there is a dearth of research on the actual therapy process and investigation of the interaction between patient and therapist. This study aims to address this paucity through the utilisation of the Adolescent Psychotherapy Q-set (APQ) to examine the early treatment period. The sample includes 69 adolescents aged 16-18 years with major depressive disorder receiving STPP as part of the First Experimental Study of Transference Work-in Teenagers (FEST-IT) trial. Of these, 21 were identified as dropouts and were compared to completers on pre-treatment patient characteristics, symptomatology, functioning, and working alliance. APQ ratings available for an early session from 16 of these drop out cases were analysed to explore the patient-therapist interaction structure. Results from the Q-factor analysis revealed three distinct interaction structures that explained 54.3% of the total variance. The first described a process of mutual trust and collaboration, the second was characterised by patient resistance and emotional detachment, the third by a mismatch and incongruence between therapist and adolescent. Comparison between the three revealed interesting differences which taken together provide further evidence that the reasons why adolescents drop out of therapy vary and are multidimensional in nature.

Non-strategic ignorance: Considering the potential for a paradigm shift in evidence-based mental health.

Randomised controlled trials form a central building block within the prevailing evidence-based mental health paradigm. Both methodology and paradigm have been widely problematised since their emergence in the mid-late twentieth century. We draw on the concept of 'strategic ignorance' to understand why the paradigm still prevails. We present focus group data gathered from 37 participants (service users, public, carers, general practitioners, commissioners) concerning the way they made sense of a randomised controlled trial of psychotherapy for treatment-resistant depression. Thematic analysis of the findings revealed an overall critique of randomised controlled trial methods which we refer to as 'non-strategic ignorance'. Specifically, participants problematised the construct of depression, unseating the premise of the randomised controlled trial; they were sceptical about the purpose and highlighted its failure to show how therapy works or who might benefit; the randomised controlled trial was seen as inadequate for informing decisions about how to select a therapy. Participants assumed the treatment would be cost-effective given the client group and nature of the therapy, irrespective of any randomised controlled trial findings. Each area of lay ('non-strategic') critique has an analogous form within the methodological expert domain. We argue that 'expert' critiques have generally failed to have paradigmatic impact because they represent strategic ignorance. Yet parallel non-strategic critiques have common sense appeal, highlighting the potential power of lay voices. The discussion considers whether the evidence-based mental health paradigm is faced with epistemological problems of such complexity that the conditions exist for a new paradigm in which service user views are central and randomised controlled trials peripheral.

Personality and outcome in individuals with treatment-resistant depression-Exploring differential treatment effects in the Tavistock Adult Depression Study (TADS).

OBJECTIVE: Although research over the past decades has investigated the impact of the personality dimensions of dependency and self-criticism on treatment outcome, little is known of how these personality features influence responsiveness to treatment in patients with severe, chronic forms of depression. METHOD: The present study uses data from the Tavistock Adult Depression Study, a randomized controlled trial investigating the effectiveness of long-term psychoanalytic psychotherapy (LTPP) compared with treatment as usual (TAU) for individuals diagnosed with treatment-resistant depression. Patients were rated with the Anaclitic-Introjective Depression Assessment Q-sort, which distinguishes between two more maladaptive (Submissive and Dismissive) and two less maladaptive (Needy and Self-Critical) subdimensions of dependent or anaclitic and self-critical or introjective depression. Multilevel modeling was used to compare individuals' growth curves of depression severity as measured by the Hamilton Rating Scale for Depression over the 18-month treatment period and 2-year follow-up. Rates of clinically significant change were also determined. RESULTS: As expected, depressed patients with more maladaptive dependent and self-critical features did not benefit from LTPP or TAU. Patients with less maladaptive self-critical features benefited from both LTPP and TAU, while those with less maladaptive dependent features showed considerable gains from LTPP but not from TAU, with medium to large effect sizes. CONCLUSIONS: Findings of this study are consistent with existing research suggesting the need to modify and tailor treatments in accordance with individuals' pretreatment personality features. Given the time and cost-intensive nature of longer-term treatment, this may be particularly important in patients with treatment-resistant depression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The economic cost of treatment-resistant depression in patients referred to a specialist service.

BACKGROUND: Patients with treatment-resistant depression (TRD) suffer very significant morbidity and are at a disadvantage concerning optimal clinical management. There are high associated societal costs. AIMS: A detailed analysis of health economic costs in the United Kingdom in a group manifesting a severe form of TRD in the 12 months before their participation in a major randomized controlled treatment trial. METHODS: The sample consisted of 118 participants from the Tavistock Adult Depression Study. Recruitment was from primary care on the basis of current major depression disorder of at least 2 years' duration and two failed treatment attempts. Service utilization was assessed based on self-report and general practitioner (GP) medical records. Generalized linear models were used to identify predictors of cost. RESULTS: All participants used GP services. Use of other doctors and practice nurses was also high. The mean total societal cost was £22 124, 80% of which was due to lost work and care required of families. Level of general functioning was found to be the most consistent predictor of costs. CONCLUSIONS: Severe forms of TRD are associated with high costs in which unpaid care and lost work predominate. Treatments that improve functioning may reduce the large degree of burden.

The Anaclitic-Introjective Depression Assessment: Development and preliminary validity of an observer-rated measure.

BACKGROUND: The two-configurations model developed by Blatt and colleagues offers a comprehensive conceptual and empirical framework for understanding depression. This model suggests that depressed patients struggle, at different developmental levels, with issues related to dependency (anaclitic issues) or self-definition (introjective issues), or a combination of both. AIMS: This paper reports three studies on the development and preliminary validation of the Anaclitic-Introjective Depression Assessment, an observer-rated assessment tool of impairments in relatedness and self-definition in clinical depression based on the item pool of the Shedler-Westen Assessment Procedure. METHOD: Study 1 describes the development of the measure using expert consensus rating and Q-methodology. Studies 2 and 3 report the assessment of its psychometric properties, preliminary reliability, and validity in a sample of 128 patients diagnosed with treatment-resistant depression. RESULTS: Four naturally occurring clusters of depressed patients were identified using Q-factor analysis, which, overall, showed meaningful and theoretically expected relationships with anaclitic/introjective prototypes as formulated by experts, as well as with clinical, social, occupational, global, and relational functioning. CONCLUSION: Taken together, findings reported in this paper provide preliminary evidence for the reliability and validity of the Anaclitic-Introjective Depression Assessment, an observer-rated measure that allows the detection of important nuanced differentiations between and within anaclitic and introjective depression.

A sea change for sick doctors - how do doctors fare after presenting to a specialist psychotherapy service?

BACKGROUND: Little is known about doctors who present to services following an episode of psychological distress. MedNet is a psycho-dynamically informed confidential self-referral service for doctors. AIMS: To examine the health and work trajectory of MedNet clients between 2002 and 2007 followed up in 2010. METHOD: We report and compare service-monitoring data for 124 doctors on engagement with health services, whether in work or not, sick leave utilised, and reported distress measured by CORE-OM at intake and at one follow-up time point. RESULTS: 95.6% of doctors continue to work and progress in their careers. 58.3% remained engaged with services. Sick leave had reduced significantly at follow-up. Distress was significantly reduced, but no differences were found with respect to social functioning and well-being. An interesting shift was observed in doctors' use of medication from treating somatic complaints towards treating mood symptoms. CONCLUSIONS: Doctors show improvements and continue to progress in their careers after a psychotherapeutically orientated intervention. A shift in doctors' perception of their difficulties is indicated from more somatic to psychological concerns. Many doctor-patients continue with ongoing professional support.

Pragmatic randomized controlled trial of long-term psychoanalytic psychotherapy for treatment-resistant depression: the Tavistock Adult Depression Study (TADS).

This pragmatic randomized controlled trial tested the effectiveness of long-term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment-as-usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long-standing major depression who had failed at least two different treatments and were considered to have treatment-resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6-monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow-up. The primary outcome measure was the 17-item version of the Hamilton Depression Rating Scale (HDRS-17), with complete remission defined as a HDRS-17 score ≤8, and partial remission defined as a HDRS-17 score ≤12. Secondary outcome measures included self-reported depression as assessed by the Beck Depression Inventory - II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation - Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42-month follow-up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow-up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer-based and self-reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long-term outcome of treatment-resistant depression. End-of-treatment evaluations or short follow-ups may miss the emergence of delayed therapeutic benefit.

Tavistock Adult Depression Study (TADS): a randomised controlled trial of psychoanalytic psychotherapy for treatment-resistant/treatment-refractory forms of depression.

BACKGROUND: Long-term forms of depression represent a significant mental health problem for which there is a lack of effective evidence-based treatment. This study aims to produce findings about the effectiveness of psychoanalytic psychotherapy in patients with treatment-resistant/treatment-refractory depression and to deepen the understanding of this complex form of depression. METHODS/DESIGN INDEX GROUP: Patients with treatment resistant/treatment refractory depression. DEFINITION & INCLUSION CRITERIA: Current major depressive disorder, 2 years history of depression, a minimum of two failed treatment attempts, ≥14 on the HRSD or ≥21 on the BDI-II, plus complex personality and/or psycho-social difficulties. EXCLUSION CRITERIA: Moderate or severe learning disability, psychotic illness, bipolar disorder, substance dependency or receipt of test intervention in the previous two years. DESIGN: Pragmatic, randomised controlled trial with qualitative and clinical components. TEST INTERVENTION: 18 months of weekly psychoanalytic psychotherapy, manualised and fidelity-assessed using the Psychotherapy Process Q-Sort. CONTROL CONDITION: Treatment as usual, managed by the referring practitioner. RECRUITMENT: GP referrals from primary care. RCT MAIN OUTCOME: HRSD (with ≤14 as remission). SECONDARY OUTCOMES: depression severity (BDI-II), degree of co-morbid disorders Axis-I and Axis-II (SCID-I and SCID-II-PQ), quality of life and functioning (GAF, CORE, Q-les-Q), object relations (PROQ2a), Cost-effectiveness analysis (CSRI and GP medical records). FOLLOW-UP: 2 years. Plus: a). Qualitative study of participants' and therapists' problem formulation, experience of treatment and of participation in trial. (b) Narrative data from semi-structured pre/post psychodynamic interviews to produce prototypes of responders and non-responders. (c) Clinical case-studies of sub-types of TRD and of change. DISCUSSION: TRD needs complex, long-term intervention and extended research follow-up for the proper evaluation of treatment outcome. This pushes at the limits of the design of randomised therapeutic trials. We discuss some of the consequent problems and suggest how they may be mitigated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40586372.

Chronic and recurrent depression in primary care: socio-demographic features, morbidity, and costs.

Background. Major depression is often chronic or recurrent and is usually treated within primary care. Little is known about the associated morbidity and costs. Objectives. To determine socio-demographic characteristics of people with chronic or recurrent depression in primary care and associated morbidity, service use, and costs. Method. 558 participants were recruited from 42 GP practices in the UK. All participants had a history of chronic major depression, recurrent major depression, or dysthymia. Participants completed questionnaires including the BDI-II, Work and Social Adjustment Scale, Euroquol, and Client Service Receipt Inventory documenting use of primary care, mental health, and other services. Results. The sample was characterised by high levels of depression, functional impairment, and high service use and costs. The majority (74%) had been treated with an anti-depressant, while few had seen a counsellor (15%) or a psychologist (3%) in the preceding three months. The group with chronic major depression was most depressed and impaired with highest service use, whilst those with dysthymia were least depressed, impaired, and costly to support but still had high morbidity and associated costs. Conclusion. This is a patient group with very significant morbidity and high costs. Effective interventions to reduce both are required.

Why do some voluntary patients feel coerced into hospitalisation? A mixed-methods study.

This study aimed to investigate factors linked to perceived coercion at admission and during treatment among voluntary inpatients. Quantitative and qualitative methods were used. Two hundred seventy patients were screened for perceived coercion at admission. Those who felt coerced into admission rated their perceived coercion during treatment a month after admission. Patient characteristics and experiences were tested as predictors of coercion. In-depth interviews on experiences leading to perceived coercion were conducted with 36 participants and analysed thematically. Thirty-four percent of patients felt coerced into admission and half of those still felt coerced a month later. No patient characteristics were associated with perceived coercion. Those whose satisfaction with treatment increased more markedly between baseline and a month later were less likely to feel coerced a month after admission. In the qualitative interviews three themes leading to perceived coercion were identified: viewing the hospital as ineffective and other treatments as more appropriate, not participating in the admission and treatment and not feeling respected. Involving patients in the decision-making and treating them with respect may reduce perceived coercion.

The fatal outcome of an individual with anorexia nervosa and Sheehan's syndrome as a result of acute enterocolitis: a case report.

OBJECTIVES: To illustrate the close association between a disturbed psychosocial up-bringing, frequent physical illness, and medical interventions. METHOD: We report a case of a 44-year-old woman with anorexia nervosa (AN) and Sheehan's syndrome who died as a result of a toxic cardiac arrest. RESULTS: The patient presented with a BMI of 13.6 kg/m(2). She refused any intensive-care treatment and died from toxic cardiac arrest. Postmortem examination revealed an acute gastroenterocolitis. DISCUSSION: The history of this patient illustrates how psychological deprivation led to eating disturbances, early pregnancy, and the life-threatening delivery of twins. This resulted in a diagnosis of Sheehan's syndrome, hepatitis C, and a ventricular ulcer. A psychosocial event triggered a late exacerbation of her AN. A helpful alliance between patient and staff did not occur as she rejected it.