Prevalence Increases as Treatments Improve: An Evolutionary Perspective on the Treatment-Prevalence Paradox in Depression.

Depression is an eminently treatable disorder that responds to psychotherapy or medications; the efficacy of each has been established in hundreds of controlled trials. Nonetheless, the prevalence of depression has increased in recent years despite the existence of efficacious treatments-a phenomenon known as the treatment-prevalence paradox. We consider several possible explanations for this paradox, which range from a misunderstanding of the very nature of depression, inflated efficacy of the established treatments, and a lack of access to efficacious delivery of treatments. We find support for each of these possible explanations but especially the notion that large segments of the population lack access to efficacious treatments that are implemented as intended. We conclude by describing the potential of using lay therapists and digital technologies to overcome this lack of access and to reach historically underserved populations and simultaneously guarantee the quality of the interventions delivered.

What we got wrong about depression and its treatment.

The paradigm is shifting with respect to how we think about depression and its treatment. Some of that shift can be attributed to new findings with respect to its epidemiology and genetics and the rest can be attributed to the incorporation of a new perspective derived from evolutionary theory. In brief, depression is far more prevalent than previously recognized with the bulk of additional cases involving individuals who do not go on to become recurrent. Nonpsychotic unipolar depression (but not bipolar mania which likely is a "true" disease) appears to be an adaptation that evolved to facilitate rumination in the service of resolving complex social problems in our ancestral past. Cognitive behavior therapy appears to structure that rumination so that patients at elevated risk for recurrence do not get "stuck" blaming themselves for their misfortunes, whereas antidepressant medications may suppress symptoms at the expense of prolonging the underlying episode such that patients remain at elevated risk for relapse whenever they try to discontinue. This means that patients not otherwise at risk for recurrence may be put on medications that they do not need and kept on them indefinitely whether they need to be or not.

Cognitive Behavioral Program for the Prevention of Depression in At-Risk Adolescents: Isolating the Effects of Dose.

The current study estimated effects of intervention dose (attendance) of a cognitive behavioral prevention (CBP) program on depression-free days (DFD) in adolescent offspring of parents with a history of depression. As part of secondary analyses of a multi-site randomized controlled trial, we analyzed the complete intention-to-treat sample of 316 at-risk adolescents ages 13-17. Youth were randomly assigned to the CBP program plus usual care (n=159) or to usual care alone (n=157). The CBP program involved 8 weekly acute sessions and 6 monthly continuation sessions. Results showed that higher CBP program dose predicted more DFDs, with a key threshold of approximately 75% of a full dose in analyses employing instrumental variable methodology to control multiple channels of bias. Specifically, attending at more than 75% of acute phase sessions led to 45.3 more DFDs over the 9-month period post randomization, which accounted for over 12% of the total follow-up days. Instrument sets were informed by study variables and external data including weather and travel burden. In contrast, conventional analysis methods failed to find a significant dose-outcome relation. Application of the instrumental variable approach, which better controls the influence of confounding, demonstrated that higher CBP program dose resulted in more DFDs.

An experimental paradigm for triggering a depressive syndrome.

Research investigating whether depression is an adaptation or a disorder has been hindered by the lack of an experimental paradigm that can test causal relationships. Moreover, studies attempting to induce the syndrome often fail to capture the suite of feelings, thoughts, and behaviors that characterize depression. An experimental paradigm for triggering depressive symptoms can improve our etiological understanding of the syndrome. The present study attempts to induce core symptoms of depression, particularly those related to rumination, in a healthy, nonclinical sample through a controlled social experiment. These symptoms are sad or depressed mood, anhedonia, feelings of worthlessness or guilt, and difficulty concentrating. One hundred and thirty-four undergraduate students were randomly assigned to either an exclusion (E) or control (C) group. Participants in the exclusion group were exposed to a modified Cyberball paradigm, designed to make them feel socially excluded, followed by a dual-interference task to assess whether their exclusion interfered with their working memory. Excluded participants: (a) self-reported a significant increase in sadness and decrease in happiness, but not anxiety or calmness; (b) scored significantly higher in four of five variables related to depressive rumination; and (c) performed significantly worse on a dual-interference task, suggesting an impaired ability to concentrate. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Long-term outcomes of once weekly v. twice weekly sessions of cognitive behavioral therapy and interpersonal psychotherapy for depression.

BACKGROUND: Twice weekly sessions of cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD) lead to less drop-out and quicker and better response compared to once weekly sessions at posttreatment, but it is unclear whether these effects hold over the long run. AIMS: Compare the effects of twice weekly v. weekly sessions of CBT and IPT for depression up to 24 months since the start of treatment. METHODS: Using a 2 × 2 factorial design, this multicentre study randomized 200 adults with MDD to once or twice weekly sessions of CBT or IPT over 16-24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II and the Longitudinal Interval Follow-up Evaluation. Intention-to-treat analyses were conducted. RESULTS: Compared with patients who received once weekly sessions, patients who received twice weekly sessions showed a significant decrease in depressive symptoms up through month 9, but this effect was no longer apparent at month 24. Patients who received CBT showed a significantly larger decrease in depressive symptoms up to month 24 compared to patients who received IPT, but the between-group effect size at month 24 was small. No differential effects between session frequencies or treatment modalities were found in response or relapse rates. CONCLUSIONS: Although a higher session frequency leads to better outcomes in the acute phase of treatment, the difference in depression severity dissipated over time and there was no significant difference in relapse.

Evidence-based practice in psychology: Context, guidelines, and action.

A science-based approach to understanding health and disease emerged gradually over the past two centuries, while the modern evidence-based approach to health care emerged only about a half-century ago. The evidence-based approach to practice in health service psychology (HSP) gained significant traction after the American Psychological Association (APA) adopted it as policy in 2005, and in 2021, APA approved the first comprehensive set of guidelines for practicing HSP in an evidence-based manner. Several authors of this 2021 set of guidelines along with an additional subject matter expert wrote the current article. This article outlines the development of evidence-based practice in psychology, discusses the strengths and weaknesses of each of the three components of evidence-based practice (i.e., best available research, clinical expertise, and patient characteristics, culture, and preferences), and highlights the complexity involved in integrating related considerations during clinical decision making. The article then discusses strategies for the systematic application of this approach in HSP to improve the effectiveness of behavioral health care and strengthen population health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cost-effectiveness of twice-weekly versus once-weekly sessions of cognitive-behavioural therapy and interpersonal psychotherapy for depression at 12 months after start of treatment: randomised controlled trial.

BACKGROUND: Cost-effective treatments are needed to reduce the burden of depression. One way to improve the cost-effectiveness of psychotherapy might be to increase session frequency, but keep the total number of sessions constant. AIM: To evaluate the cost-effectiveness of twice-weekly compared with once-weekly psychotherapy sessions after 12 months, from a societal perspective. METHOD: An economic evaluation was conducted alongside a randomised controlled trial comparing twice-weekly versus once-weekly sessions of psychotherapy (cognitive-behavioural therapy or interpersonal psychotherapy) for depression. Missing data were handled by multiple imputation. Statistical uncertainty was estimated with bootstrapping and presented with cost-effectiveness acceptability curves. RESULTS: Differences between the two groups in depressive symptoms, physical and social functioning, and quality-adjusted life-years (QALY) at 12-month follow-up were small and not statistically significant. Total societal costs in the twice-weekly session group were higher, albeit not statistically significantly so, than in the once-weekly session group (mean difference €2065, 95% CI -686 to 5146). The probability that twice-weekly sessions are cost-effective compared with once-weekly sessions was 0.40 at a ceiling ratio of €1000 per point improvement in Beck Depression Inventory-II score, 0.32 at a ceiling ratio of €50 000 per QALY gained, 0.23 at a ceiling ratio of €1000 per point improvement in physical functioning score and 0.62 at a ceiling ratio of €1000 per point improvement in social functioning score. CONCLUSIONS: Based on the current results, twice-weekly sessions of psychotherapy for depression are not cost-effective over the long term compared with once-weekly sessions.

Examining Predictors of Depression and Anxiety Symptom Change in Cognitive Behavioral Immersion: Observational Study.

BACKGROUND: Depressive and anxiety disorders are the most common mental disorders, and there is a critical need for effective, affordable, and accessible interventions. Cognitive Behavioral Immersion (CBI) is a novel group-based cognitive behavioral skills training program delivered by lay coaches in the metaverse that can be accessed through various modalities including virtual reality (VR) head-mounted displays or flat-screen devices. Combining its ability to offer empirically supported therapy skills in a digital setting that can still facilitate interpersonal variables (eg, working alliance and sense of social support) with the aid of lay coaches, CBI has the potential to help fill this critical need. OBJECTIVE: This study had 2 primary aims. First, we aimed to examine changes in depression and anxiety symptoms in a sample of individuals who participated in CBI. Second, we aimed to examine 2 interpersonal process variables (working alliance and web-based social support) as predictors of symptom changes. We predicted CBI participants would experience depression and anxiety symptom improvements and that such improvements would be associated with an increase in both interpersonal process variables. METHODS: The study sample consists of 127 participants who endorsed clinical levels of depression or anxiety symptoms during their first CBI session and attended at least 2 sessions. Participants were asked to complete self-report measures of depression symptoms, anxiety symptoms, alliance, and web-based social support throughout their participation in CBI. RESULTS: Repeated measures ANOVAs determined that depression and anxiety symptom scores differed significantly across sessions (Ps<.01). We also found participants' web-based social support predicted improvement in depression symptoms (P=.01), but neither the alliance nor web-based social support predicted change in anxiety symptoms (Ps>.05). We also observed a significant difference in anxiety symptoms between participants who used a VR head-mounted display to access CBI and those who did not, such that participants who used VR head-mounted displays endorsed lower anxiety symptoms than those who did not at nearly every session (P=.04). CONCLUSIONS: Participation in CBI is associated with both depression and anxiety symptom improvement. Web-based social support may play an important role in fostering changes in depression symptoms. Future studies are encouraged to continue examining the process of change in CBI with special attention paid to methods that can elucidate causal mechanisms of change.

Effects of an Artificial Intelligence Platform for Behavioral Interventions on Depression and Anxiety Symptoms: Randomized Clinical Trial.

BACKGROUND: The need for scalable delivery of mental health care services that are efficient and effective is now a major public health priority. Artificial intelligence (AI) tools have the potential to improve behavioral health care services by helping clinicians collect objective data on patients' progress, streamline their workflow, and automate administrative tasks. OBJECTIVE: The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an AI platform for behavioral health in facilitating better clinical outcomes for patients receiving outpatient therapy. METHODS: The study was conducted at a community-based clinic in the United States. Participants were 47 adults referred for outpatient, individual cognitive behavioral therapy for a main diagnosis of a depressive or anxiety disorder. The platform provided by Eleos Health was compared to a treatment-as-usual (TAU) approach during the first 2 months of therapy. This AI platform summarizes and transcribes the therapy session, provides feedback to therapists on the use of evidence-based practices, and integrates these data with routine standardized questionnaires completed by patients. The information is also used to draft the session's progress note. Patients were randomized to receive either therapy provided with the support of an AI platform developed by Eleos Health or TAU at the same clinic. Data analysis was carried out based on an intention-to-treat approach from December 2022 to January 2023. The primary outcomes included the feasibility and acceptability of the AI platform. Secondary outcomes included changes in depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7) scores as well as treatment attendance, satisfaction, and perceived helpfulness. RESULTS: A total of 72 patients were approached, of whom 47 (67%) agreed to participate. Participants were adults (34/47, 72% women and 13/47, 28% men; mean age 30.64, SD 11.02 years), with 23 randomized to the AI platform group, and 24 to TAU. Participants in the AI group attended, on average, 67% (mean 5.24, SD 2.31) more sessions compared to those in TAU (mean 3.14, SD 1.99). Depression and anxiety symptoms were reduced by 34% and 29% in the AI platform group versus 20% and 8% for TAU, respectively, with large effect sizes for the therapy delivered with the support of the AI platform. No group difference was found in 2-month treatment satisfaction and perceived helpfulness. Further, therapists using the AI platform submitted their progress notes, on average, 55 hours earlier than therapists in the TAU group (t=-0.73; P<.001). CONCLUSIONS: In this randomized controlled trial, therapy provided with the support of Eleos Health demonstrated superior depression and anxiety outcomes as well as patient retention, compared with TAU. These findings suggest that complementing the mental health services provided in community-based clinics with an AI platform specializing in behavioral treatment was more effective in reducing key symptoms than standard therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05745103; https://classic.clinicaltrials.gov/ct2/show/NCT05745103.

Cognitive Behavioral Immersion for Substance Use Disorders: A Feasibility and Pilot Study of a Peer-Based Coaching Program in the Metaverse.

Introduction: Cognitive Behavioral Immersion (CBI) is a novel cognitive-behavioral skills program delivered by lay coaches in the metaverse through immersive virtual reality technology. Objectives: The objective for this study was to run a feasibility and pilot study of CBI for individuals in recovery from a substance use disorder. Methods: Data from 48 participants were used and program usage was assessed. Participants were asked to complete questionnaires assessing affect, perceived online social support, and group therapy alliance throughout their participation in the program. Structured qualitative interviews were also conducted with a subset of participants (n = 11) to understand the feasibility of the novel program. Results: Participants experienced a significant increase in their positive affect and non-significant decrease in their negative affect during their most recently attended session. Participants also experienced a nonsignificant increase in online social support across their participation in the program. Structured qualitative interviews revealed eight primary themes, including both advantages (community, psychoeducational impact, immersion, comparability with other interventions, coping in the pandemic, and anonymity) and areas of improvement (challenges and technological usability) of the program. Conclusion: This study provides preliminary support for the feasibility and potential effects of CBI and its incorporation of lay coaches to lead cognitive-behavioral skills groups in the metaverse. Future research is encouraged to examine the feasibility and efficacy of this program for a broader array of clinical presentations.

Cognitive restructuring and psychotherapy outcome: A meta-analytic review.

Cognitive restructuring (CR) is one method that is hypothesized to play a role in the process of change across many psychotherapies and for a variety of clinical presentations. In this article, we define and illustrate CR. We then present a meta-analysis of four studies (including a total of 353 clients) examining the effect of CR measured within session on psychotherapy outcomes. The overall CR-outcome association was r = .35 (95% CI [.24, .44]; equivalent of d = 0.85). While more research on CR and immediate psychotherapy outcomes is needed, there is accumulating encouraging evidence regarding the therapeutic effect of CR. We conclude by advancing implications for clinical training and therapeutic practices. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Can integrating the Memory Support Intervention into cognitive therapy improve depression outcome? A randomized controlled trial.

We investigated if improving a patient's memory for the content of their treatment, via the Memory Support Intervention, improves illness course and functional outcomes. The platform for investigating this question was major depressive disorder (MDD) and cognitive therapy (CT). Adults diagnosed with MDD (N = 178) were randomly allocated to CT + Memory Support (n = 91) or CT-as-usual (n = 87). Both treatments were comprised of 20-26, 50-min sessions over 16 weeks. Blind assessments were conducted before and immediately following treatment (post-treatment) and 6 months later (6FU). Patient memory for treatment, assessed with a free recall task, was higher in CT + Memory Support for past session recall at post-treatment. Both treatment arms were associated with reductions in depressive symptoms and functional impairment except: CT + Memory Support exhibited lower depression severity at 6FU (b = -3.09, p = 0.050, d = -0.27), and greater reduction in unhealthy days from baseline to 6FU (b = -4.21, p = 0.010, d = -1.07), compared to CT-as-usual. While differences in illness course and functional outcomes between the two treatment arms were limited, it is possible that future analyses of the type of memory supports and longer follow-up may yield more encouraging outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01790919. Registered October 6, 2016.

Efficacy and moderators of cognitive therapy versus behavioural activation for adults with depression: study protocol of a systematic review and meta-analysis of individual participant data.

BACKGROUND: Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data. AIMS: This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602). METHOD: Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes. CONCLUSIONS: To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.

Peer-led family-centred problem management plus for immigrants (PMP-I) for mental health promotion among immigrants in USA: protocol for a pilot, randomised controlled feasibility trial.

INTRODUCTION: Research is needed to investigate preventive strategies to reduce mental health burden and assess effective implementation among immigrants. Problem management plus (PMP) is a low-intensity multicomponent psychological intervention developed by the World Health Organization (WHO) that trained laypeople can deliver. PMP has been adapted as a prevention intervention and developed as PMP for immigrants (PMP-I), including psychoeducation, problem-solving, behavioural activations and mind-body exercise, to address immigrants' multiple stressors. This pilot trial aims to assess the feasibility and acceptability of PMP-I and provide a preliminary estimate of the difference between PMP-I versus community support services pamphlets on the primary outcomes of interest (stress, anxiety and depressive symptoms) to inform the design of a large-scale intervention. METHODS AND ANALYSIS: The feasibility and acceptability of PMP-I will be assessed by measuring recruitment, session attendance, retention rates, programme acceptability and the fidelity of intervention delivery. This pilot trial will test preliminary effects of PMP-I vs community support services pamphlets in a randomised controlled trial (N=232 participants from 116 families (2 members/family); 58 families randomised to condition intervention or control) on stress, anxiety and depressive symptoms (primary outcomes), chronic physiological stress assessed in hair cortisol (secondary outcomes), and coping, family conflict resolution, and social networking (targets), with assessment at baseline, postintervention and 3-month postintervention. Eligibility criteria for the primary study participants include Bhutanese ≥18 years resettled in Massachusetts with a score of ≤14 on the Patient Health Questionnaire-9. All family members will be invited to participate in the family-based intervention (one session/week for 5 weeks). Multilevel modelling will compare the longitudinal change in outcomes for each treatment arm. ETHICS AND DISSEMINATION: The Institutional Review Board of the University of Massachusetts Amherst approved this study (Protocol: 1837). Written informed consent will be obtained from all participants. The study results will be used to inform the design of a large-scale intervention and will be disseminated in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT04453709.

Components of smartphone cognitive-behavioural therapy for subthreshold depression among 1093 university students: a factorial trial.

BACKGROUND: Internet-based cognitive-behavioural therapy (iCBT) is effective for subthreshold depression. However, which skills provided in iCBT packages are more effective than others is unclear. Such knowledge can inform construction of more effective and efficient iCBT programmes. OBJECTIVE: To examine the efficacy of five components of iCBT for subthreshold depression. METHODS: We conducted an factorial trial using a smartphone app, randomly allocating presence or absence of five iCBT skills including self-monitoring, behavioural activation (BA), cognitive restructuring (CR), assertiveness training (AT) and problem-solving. Participants were university students with subthreshold depression. The primary outcome was the change on the Patient Health Questionnaire-9 (PHQ-9) from baseline to week 8. Secondary outcomes included changes in CBT skills. FINDINGS: We randomised a total of 1093 participants. In all groups, participants had a significant PHQ-9 reduction from baseline to week 8. Depression reduction was not significantly different between presence or absence of any component, with corresponding standardised mean differences (negative values indicate specific efficacy in favour of the component) ranging between -0.04 (95% CI -0.16 to 0.08) for BA and 0.06 (95% CI -0.06 to 0.18) for AT. Specific CBT skill improvements were noted for CR and AT but not for the others. CONCLUSIONS: There was significant reduction in depression for all participants regardless of the presence and absence of the examined iCBT components. CLINICAL IMPLICATION: We cannot yet make evidence-based recommendations for specific iCBT components. We suggest that future iCBT optimisation research should scrutinise the amount and structure of components to examine. TRIAL REGISTRATION NUMBER: UMINCTR-000031307.

Self-critical perfectionism, dependency and entropy during cognitive behavioural therapy for depression.

OBJECTIVES: This study examined whether 'personality vulnerability' (i.e., self-critical perfectionism or dependency) predicts the trajectory of change, as well as variability and instability (i.e., entropy) of symptoms, during cognitive behaviour therapy (CBT) for depression. DESIGN: Study participants were outpatients (N = 312) experiencing a primary mood disorder. Participants received CBT for depression group sessions over 15 weeks. Self-report measures of self-critical perfectionism, dependency, and depression were collected longitudinally. METHODS: A latent growth mixture modelling (LGMM) statistical approach was used to evaluate the presence of latent classes of individuals based on their longitudinal pattern of symptom change during CBT and to evaluate whether baseline self-critical perfectionism or dependency predicts class membership. A Latent Acceleration Score (LAS) model evaluated whether perfectionism or dependency led to variability in depression symptom change (e.g., velocity) by considering changes in velocity (e.g., acceleration and/or deceleration). RESULTS: LGMM indicated the presence of two latent classes that represent symptom improvement (N = 239) or minimal symptom improvement over time (N = 73). Elevated baseline self-critical perfectionism, but not dependency, predicted a greater likelihood of membership in the class of participants who demonstrated minimal symptom improvement over time. The second analysis examined whether baseline self-critical perfectionism also predicts depression symptom variability and instability. The LAS perfectionism model demonstrated that perfectionism accelerates depression symptom change during the first seven sessions of treatment, then has a decelerating effect on depression symptom change. CONCLUSIONS: Results indicated that higher baseline self-critical perfectionism predicted higher variability and instability in depression symptoms and variability in acceleration and deceleration, over the course of treatment.

Socioeconomic Indicators of Treatment Prognosis for Adults With Depression: A Systematic Review and Individual Patient Data Meta-analysis.

Importance: Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression. Objective: To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis for adults treated for depression in primary care, independent of treatment and after accounting for clinical prognostic factors. Data Sources: The Embase, International Pharmaceutical Abstracts, MEDLINE, PsycINFO, and Cochrane (CENTRAL) databases were searched from database inception to October 8, 2021. Study Selection: Inclusion criteria were as follows: randomized clinical trials that used the Revised Clinical Interview Schedule (CIS-R; the most common comprehensive screening and diagnostic measure of depressive and anxiety symptoms in primary care randomized clinical trials), measured socioeconomic factors at baseline, and sampled patients with unipolar depression who sought treatment for depression from general physicians/practitioners or who scored 12 or more points on the CIS-R. Exclusion criteria included patients with depression secondary to a personality or psychotic disorder or neurologic condition, studies of bipolar or psychotic depression, studies that included children or adolescents, and feasibility studies. Studies were independently assessed against inclusion and exclusion criteria by 2 reviewers. Data Extraction and Synthesis: Data were extracted and cleaned by data managers for each included study, further cleaned by multiple reviewers, and cross-checked by study chief investigators. Risk of bias and quality were assessed using the Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Individual Participant Data (PRISMA-IPD) reporting guidelines. Main Outcomes and Measures: Depressive symptoms at 3 to 4 months after baseline. Results: This systematic review and individual patient data meta-analysis identified 9 eligible studies that provided individual patient data for 4864 patients (mean [SD] age, 42.5 (14.0) years; 3279 women [67.4%]). The 2-stage random-effects meta-analysis end point depressive symptom scale scores were 28% (95% CI, 20%-36%) higher for unemployed patients than for employed patients and 18% (95% CI, 6%-30%) lower for patients who were homeowners than for patients living with family or friends, in hostels, or homeless, which were equivalent to 4.2 points (95% CI, 3.6-6.2 points) and 2.9 points (95% CI, 1.1-4.9 points) on the Beck Depression Inventory II, respectively. Financial strain and educational attainment were associated with prognosis independent of treatment, but unlike employment and housing status, there was little evidence of associations after adjusting for clinical prognostic factors. Conclusions and Relevance: Results of this systematic review and meta-analysis revealed that unemployment was associated with a poor prognosis whereas home ownership was associated with improved prognosis. These differences were clinically important and independent of the type of treatment received. Interventions that address employment or housing difficulties could improve outcomes for patients with depression.

Clinical research challenges posed by difficult-to-treat depression.

Approximately one-third of individuals in a major depressive episode will not achieve sustained remission despite multiple, well-delivered treatments. These patients experience prolonged suffering and disproportionately utilize mental and general health care resources. The recently proposed clinical heuristic of 'difficult-to-treat depression' (DTD) aims to broaden our understanding and focus attention on the identification, clinical management, treatment selection, and outcomes of such individuals. Clinical trial methodologies developed to detect short-term therapeutic effects in treatment-responsive populations may not be appropriate in DTD. This report reviews three essential challenges for clinical intervention research in DTD: (1) how to define and subtype this heterogeneous group of patients; (2) how, when, and by what methods to select, acquire, compile, and interpret clinically meaningful outcome metrics; and (3) how to choose among alternative clinical trial design options to promote causal inference and generalizability. The boundaries of DTD are uncertain, and an evidence-based taxonomy and reliable assessment tools are preconditions for clinical research and subtyping. Traditional outcome metrics in treatment-responsive depression may not apply to DTD, as they largely reflect the only short-term symptomatic change and do not incorporate durability of benefit, side effect burden, or sustained impact on quality of life or daily function. The trial methodology will also require modification as trials will likely be of longer duration to examine the sustained impact, raising complex issues regarding control group selection, blinding and its integrity, and concomitant treatments.

Life events and treatment prognosis for depression: A systematic review and individual patient data meta-analysis.

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