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.

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.

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.

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.

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.

The contribution of depressive 'disorder characteristics' to determinations of prognosis for adults with depression: an individual patient data meta-analysis.

BACKGROUND: This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care. METHODS: We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted. RESULTS: Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3-4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3-4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions. CONCLUSIONS: When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.

Is social support pre-treatment associated with prognosis for adults with depression in primary care?

OBJECTIVE: Depressed patients rate social support as important for prognosis, but evidence for a prognostic effect is lacking. We aimed to test the association between social support and prognosis independent of treatment type, and the severity of depression, and other clinical features indicating a more severe illness. METHODS: Individual patient data were collated from all six eligible RCTs (n = 2858) of adults seeking treatment for depression in primary care. Participants were randomized to any treatment and completed the same baseline assessment of social support and clinical severity factors. Two-stage random effects meta-analyses were conducted. RESULTS: Social support was associated with prognosis independent of randomized treatment but effects were smaller when adjusting for depressive symptoms and durations of depression and anxiety, history of antidepressant treatment, and comorbid panic disorder: percentage decrease in depressive symptoms at 3-4 months per z-score increase in social support = -4.14(95%CI: -6.91 to -1.29). Those with a severe lack of social support had considerably worse prognoses than those with no lack of social support: increase in depressive symptoms at 3-4 months = 14.64%(4.25% to 26.06%). CONCLUSIONS: Overall, large differences in social support pre-treatment were associated with differences in prognostic outcomes. Adding the Social Support scale to clinical assessments may be informative, but after adjusting for routinely assessed clinical prognostic factors the differences in prognosis are unlikely to be of a clinically important magnitude. Future studies might investigate more intensive treatments and more regular clinical reviews to mitigate risks of poor prognosis for those reporting a severe lack of social support.

Social and Emotional Wellbeing (SEW) Intervention for Mental Health Promotion Among Resettled Bhutanese Adults in Massachusetts.

Preventative behavioral interventions aimed at reducing mental problems among refugees are limited. We assessed the effect of a Social and Emotional Wellbeing (SEW) intervention on health-promoting behaviors (coping, social-networking, and conflict-resolution) and health-outcomes (stress, anxiety, and depression) among resettled Bhutanese adults in Western Massachusetts. The study was a community-based SEW intervention with pre-posttest evaluation among 44 Bhutanese adults in Western Massachusetts. The SEW is a culturally tailored 5-week, once-weekly health-education, problem solving, and mind-body exercise program to promote stress management skills. We used validated scales to measure outcomes. Mean scores of mental problems decreased by 5.9 for depression, 9.0 for anxiety, and 5.0 for stress post-intervention (p < 0.01). Mean scores increased by 27.3 for coping, 10.6 for social support, and 20.4 for conflict-resolution. Mean social-network scores increased by 4.6 for family, 4.7 for friends, and 1.8 for community networks (p < 0.01). Our Bhutanese participants reported improvement in their mental health after attending SEW intervention.

Effects of psychological treatment of mental health problems in pregnant women to protect their offspring: randomised controlled trial.

BACKGROUND: Perinatal depression and anxiety are associated with unfavourable child outcomes. AIMS: To assess among women with antenatal depression or anxiety the effectiveness of prenatally initiated cognitive-behavioural therapy (CBT) on mother and child compared with care as usual (CAU). Trial registration: Netherlands Trial Register number NTR2242. METHOD: Pregnant women (n = 282) who screened positive for symptoms of depression and/or anxiety were randomised to either CBT (n = 140) or CAU (n = 142). The primary outcome was child behavioural and emotional problems at age 18 months, assessed using the Child Behavior Checklist (CBCL). Secondary outcomes were maternal symptoms during and up to 18 months after pregnancy, neonatal outcomes, mother-infant bonding and child cognitive and motor development at age 18 months. RESULTS: In total, 94 (67%) women in the CBT group and 98 (69%) in the CAU group completed the study. The mean CBCL Total Problems score was non-significantly higher in the CBT group than in the CAU group (mean difference: 1.38 (95% CI -1.82 to 4.57); t = 0.85, P = 0.399). No effects on secondary outcomes were observed except for depression and anxiety, which were higher in the CBT group than in the CAU group at mid-pregnancy. A post hoc analysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group. CONCLUSIONS: Prenatally initiated CBT did not improve maternal symptoms or child outcomes among non-help-seeking women with antenatal depression or anxiety. Our findings are not in line with present recommendations for universal screening and treatment for antenatal depression or anxiety, and future work may include the relevance of baseline help-seeking.

The effects of once- versus twice-weekly sessions on psychotherapy outcomes in depressed patients.

BACKGROUND: It is unclear what session frequency is most effective in cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression. AIMS: Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression. METHOD: We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients 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 at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted. RESULTS: Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates (n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00-2.18). CONCLUSIONS: In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes.

The antidepressant standoff: why it continues and how to resolve it.

BACKGROUND: Antidepressant medications (ADMs) are widely used and long-term use is increasing. Given this extensive use and recommendation of ADMs in guidelines, one would expect ADMs to be universally considered effective. Surprisingly, that is not the case; fierce debate on their benefits and harms continues. This editorial seeks to understand why the controversy continues and how consensus can be achieved. METHODS: 'Position' paper. Critical analysis and synthesis of relevant literature. RESULTS: Advocates point at ADMs impressive effect size (number needed to treat, NNT = 6-8) in acute phase treatment and continuation/maintenance ADM treatment prevention relapse/recurrence in acute phase ADM responders (NNT = 3-4). Critics point at the limited clinically significant surplus value of ADMs relative to placebo and argue that effectiveness is overstated. We identified multiple factors that fuel the controversy: certainty of evidence is low to moderate; modest efficacy on top of strong placebo effects allows critics to focus on small net efficacy and advocates on large gross efficacy; ADM withdrawal symptoms masquerade as relapse/recurrence; lack of association between ADM treatment and long-term outcome in observational databases. Similar problems affect psychological treatments as well, but less so. We recommend four approaches to resolve the controversy: (1) placebo-controlled trials with relevant long-term outcome assessments, (2) inventive analyses of observational databases, (3) patient cohort studies including effect moderators to improve personalized treatment, and (4) psychological treatments as universal first-line treatment step. CONCLUSIONS: Given the public health significance of depression and increased long-term ADM usage, new approaches are needed to resolve the controversy.

Temporal pathways of change in two randomized controlled trials for depression and harmful drinking in Goa, India.

BACKGROUND: The current study explored the temporal pathways of change within two treatments, the Healthy Activity Program (HAP) for depression and the Counselling for Alcohol Problems (CAP) Program for harmful drinking. METHODS: The study took place in the context of two parallel randomized controlled trials in Goa, India. N = 50 random participants who met a priori criteria were selected from each treatment trial and examined for potential direct and mediational pathways. In HAP, we examined the predictive roles of therapy quality and patient-reported activation, assessing whether activation mediated the effects of therapy quality on depression (Patient Health Questionnaire-9) outcomes. In CAP, we examined the predictive roles of therapy quality and patient change- and counter-change-talk, assessing whether change- or counter-change-talk mediated the effects of therapy quality on daily alcohol consumption. RESULTS: In HAP, therapy quality (both general and treatment-specific skills) was associated with patient activation; patient activation but not therapy quality significantly predicted depression outcomes, and patient activation mediated the effects of higher general skills on subsequent clinical outcomes [a × b = -2.555, 95% confidence interval (CI) -5.811 to -0.142]. In CAP, higher treatment-specific skills, but not general skills, were directly associated with drinking outcomes, and reduced levels of counter-change talk both independently predicted, and mediated the effects of higher general skills on, reduced alcohol consumption (a × b = -24.515, 95% CI -41.190 to -11.060). Change talk did not predict alcohol consumption and was not correlated with counter-change talk. CONCLUSION: These findings suggest that therapy quality in early sessions operated through increased patient activation and reduced counter-change talk to reduce depression and harmful drinking respectively.

Validation of the Health-Related Felt Stigma and Concealment Questionnaire.

OBJECTIVE: Stigma is associated with many health conditions, including chronic pain. Research on health-related stigma is limited by the lack of validated instruments that distinguish among various stigma-related constructs. We aimed to develop and validate such a measure for pediatric functional abdominal pain (FAP). Felt stigma (FS) was defined as comprising both perceived and internalized stigma. Stigma concealment (SC) was defined as efforts by stigmatized individuals to prevent others from learning of their condition. METHODS: Using a theory-driven approach, we adapted items from existing self-report measures of stigma to construct the health-related FS and Concealment Questionnaire (FSC-Q). Patients with FAP (N = 179, ages 11-17) completed the preliminary FSC-Q and health-related measures hypothesized to be associated with stigma. Cognitive interviewing and exploratory factor analysis (EFA) informed the final version of the measure. RESULTS: EFA identified a 2-factor model comprised of FS and SC. The FS and SC scales exhibited good internal consistency and construct validity. Consistent with study hypotheses, both factors were significantly associated with anxiety, depression, pain catastrophizing, pain threat, physical symptoms, and pain interference/disability. Higher FS was associated with higher mental healthcare utilization. The subset of participants meeting criteria for irritable bowel syndrome (IBS) reported higher FS and SC compared with those without IBS. CONCLUSION: The FSC-Q may help advance research on health-related stigma in FAP and other chronic health conditions by allowing for assessment of distinct stigma-related constructs.

Interpersonal Psychotherapy Versus Cognitive Therapy for Depression: How They Work, How Long, and for Whom-Key Findings From an RCT.

OBJECTIVE: Although the effectiveness of interpersonal psychotherapy (IPT) and cognitive therapy (CT) for major depression has been established, little is known about how and for whom they work and how they compare in the long term. The latter is especially relevant for IPT because research on its long-term effects has been limited. This overview paper summarizes findings from a Dutch randomized controlled trial on the effects and mechanisms of change of IPT versus CT for major depression. METHODS: Adult outpatients with depression (N=182) were randomly assigned to CT (N=76), IPT (N=75), or a 2-month waitlist control group followed by patient's treatment of choice (N=31). The primary outcome was depression severity. Other outcomes were quality of life, social and general psychological functioning, and scores on various mechanism measures. Interventions were compared at the end of treatment and up to 17 months follow-up. RESULTS: On average, IPT and CT were both superior to waitlist, and their outcomes did not differ significantly from one another. However, the pathway through which change occurred appeared to differ. For a majority of participants, one of the interventions was predicted to be more beneficial than the other. No support for the theoretical models of change was found. CONCLUSIONS: Outcomes of IPT and CT did not appear to differ significantly. IPT may have an enduring effect not different from that of CT. The field would benefit from further refinement of study methods to disentangle mechanisms of change and from advances in the field of personalized medicine (i.e., person-specific analyses and treatment selection methods).

Long-term outcomes of acute treatment with cognitive therapy v. interpersonal psychotherapy for adult depression: follow-up of a randomized controlled trial.

BACKGROUND: Although equally efficacious in the acute phase, it is not known how cognitive therapy (CT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD) compare in the long run. This study examined the long-term outcomes of CT v. IPT for MDD. METHODS: One hundred thirty-four adult (18-65) depressed outpatients who were treated with CT (n = 69) or IPT (n = 65) in a large open-label randomized controlled trial (parallel group design; computer-generated block randomization) were monitored across a 17-month follow-up phase. Mixed regression was used to determine the course of self-reported depressive symptom severity (Beck Depression Inventory II; BDI-II) after treatment termination, and to test whether CT and IPT differed throughout the follow-up phase. Analyses were conducted for the total sample (n = 134) and for the subsample of treatment responders (n = 85). Furthermore, for treatment responders, rates of relapse and sustained response were examined for self-reported (BDI-II) and clinician-rated (Longitudinal Interval Follow-up Evaluation; LIFE) depression using Cox regression. RESULTS: On average, the symptom reduction achieved during the 7-month treatment phase was maintained across follow-up (7-24 months) for CT and IPT, both in the total sample and in the responder sample. Two-thirds (67%) of the treatment responders did not relapse across the follow-up period on the BDI-II. Relapse rates assessed with the LIFE were somewhat lower. No differential effects between conditions were found. CONCLUSIONS: Patients who responded to IPT were no more likely to relapse following treatment termination than patients who responded to CT. Given that CT appears to have a prophylactic effect following successful treatment, our findings suggest that IPT might have a prophylactic effect as well.

Where are the breaks in translation from theory to clinical practice (and back) in addressing depression? An empirical graph-theoretic approach.

BACKGROUND: Research in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents. METHODS: We used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents). RESULTS: These analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected. CONCLUSIONS: These analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups.

Component studies of psychological treatments of adult depression: A systematic review and meta-analysis.

OBJECTIVES: A recent report from the US Institute of Medicine indicated that identifying core elements of psychosocial interventions is a key step in successfully bringing evidence-based psychosocial interventions into clinical practice. Component studies have the best design to examine these core elements. Earlier reviews resulted in heterogeneous sets of studies and probably missed many studies. METHODS: We conducted a comprehensive search of component studies on psychotherapies for adult depression and included 16 studies with 22 comparisons. RESULTS: Fifteen components were examined of which four were examined in more than one comparison. The pooled difference between the full treatments and treatments with one component removed was g = 0.21 (95% CI: 0.03∼0.39). One study had sufficient statistical power to detect a small effect size and found that adding emotion regulation skills increased the effects of CBT. None of the other studies had enough power to detect an effect size smaller than g = 0.55. Only one study had low risk of bias. CONCLUSIONS: The currently available component studies do not have the statistical power nor the quality to draw any meaningful conclusion about key ingredients of psychotherapies for adult depression.

Cross-sectional networks of depressive symptoms before and after antidepressant medication treatment.

PURPOSE: Recent reviews have questioned the efficacy of selective serotonin reuptake inhibitors (SSRIs) above placebo response, and their working mechanisms remain unclear. New approaches to understanding the effects of SSRIs are necessary to enhance their efficacy. The aim of this study was to explore the possibilities of using cross-sectional network analysis to increase our understanding of symptom connectivity before and after SSRI treatment. METHODS: In two randomized controlled trials (total N = 178), we estimated Gaussian graphical models among 20 symptoms of the Beck Depression Inventory-II before and after 8 weeks of treatment with the SSRI paroxetine. Networks were compared on connectivity, community structure, predictability (proportion explained variance), and strength centrality (i.e., connectedness to other symptoms in the network). RESULTS: Symptom severity for all individual BDI-II symptoms significantly decreased over 8 weeks of SSRI treatment, whereas interconnectivity and predictability of the symptoms significantly increased. At baseline, three communities were detected; five communities were detected at week 8. CONCLUSIONS: Findings suggest the effects of SSRIs can be studied using the network approach. The increased connectivity, predictability, and communities at week 8 may be explained by the decrease in depressive symptoms rather than specific effects of SSRIs. Future studies with larger samples and placebo controls are needed to offer insight into the effects of SSRIs. TRIAL REGISTRATION: The trials described in this manuscript were funded by the NIMH. Pennsylvania/Vanderbilt study: 5 R10 MH55877 ( https://projectreporter.nih.gov/project_info_description.cfm?aid=6186633&icde=28344168&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC&MMOpt= ). Washington study: R01 MH55502 ( https://projectreporter.nih.gov/project_info_description.cfm?aid=2034618&icde=28344217&ddparam=&ddvalue=&ddsub=&cr=5&csb=default&cs=ASC ).

Sustained effectiveness and cost-effectiveness of the Healthy Activity Programme, a brief psychological treatment for depression delivered by lay counsellors in primary care: 12-month follow-up of a randomised controlled trial.

BACKGROUND: The Healthy Activity Programme (HAP), a brief behavioural intervention delivered by lay counsellors, enhanced remission over 3 months among primary care attendees with depression in peri-urban and rural settings in India. We evaluated the sustainability of the effects after treatment termination, the cost-effectiveness of HAP over 12 months, and the effects of the hypothesized mediator of activation on clinical outcomes. METHODS AND FINDINGS: Primary care attendees aged 18-65 years screened with moderately severe to severe depression on the Patient Health Questionnaire 9 (PHQ-9) were randomised to either HAP plus enhanced usual care (EUC) (n = 247) or EUC alone (n = 248), of whom 95% completed assessments at 3 months, and 91% at 12 months. Primary outcomes were severity on the Beck Depression Inventory-II (BDI-II) and remission on the PHQ-9. HAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up (difference in mean BDI-II score between 3 and 12 months = -0.34; 95% CI -2.37, 1.69; p = 0.74), with lower symptom severity scores than participants who received EUC alone (adjusted mean difference in BDI-II score = -4.45; 95% CI -7.26, -1.63; p = 0.002) and higher rates of remission (adjusted prevalence ratio [aPR] = 1.36; 95% CI 1.15, 1.61; p < 0.009). They also fared better on most secondary outcomes, including recovery (aPR = 1.98; 95% CI 1.29, 3.03; p = 0.002), any response over time (aPR = 1.45; 95% CI 1.27, 1.66; p < 0.001), higher likelihood of reporting a minimal clinically important difference (aPR = 1.42; 95% CI 1.17, 1.71; p < 0.001), and lower likelihood of reporting suicidal behaviour (aPR = 0.71; 95% CI 0.51, 1.01; p = 0.06). HAP plus EUC also had a marginal effect on WHO Disability Assessment Schedule score at 12 months (aPR = -1.58; 95% CI -3.33, 0.17; p = 0.08); other outcomes (days unable to work, intimate partner violence toward females) did not statistically significantly differ between the two arms. Economic analyses indicated that HAP plus EUC was dominant over EUC alone, with lower costs and better outcomes; uncertainty analysis showed that from this health system perspective there was a 95% chance of HAP being cost-effective, given a willingness to pay threshold of Intl$16,060-equivalent to GDP per capita in Goa-per quality-adjusted life year gained. Patient-reported behavioural activation level at 3 months mediated the effect of the HAP intervention on the 12-month depression score (ß = -2.62; 95% CI -3.28, -1.97; p < 0.001). Serious adverse events were infrequent, and prevalence was similar by arm. We were unable to assess possible episodes of remission and relapse that may have occurred between our outcome assessment time points of 3 and 12 months after randomisation. We did not account for or evaluate the effect of mediators other than behavioural activation. CONCLUSIONS: HAP's superiority over EUC at the end of treatment was largely stable over time and was mediated by patient activation. HAP provides better outcomes at lower costs from a perspective covering publicly funded healthcare services and productivity impacts on patients and their families. TRIAL REGISTRATION: ISRCTN registry ISRCTN95149997.

Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial.

BACKGROUND: Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy-cognitive behavioural therapy (CBT)-is complex and costly. A simpler therapy-behavioural activation (BA)-might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression. METHODS: In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity [Patient Health Questionnaire 9 (PHQ-9) score of <19 vs ≥19], antidepressant use, and recruitment site) to BA from junior mental health workers or CBT from psychological therapists. Randomisation done at the Peninsula Clinical Trials Unit was concealed from investigators. Treatment was given open label, but outcome assessors were masked. The primary outcome was depression symptoms according to the PHQ-9 at 12 months. We analysed all those who were randomly allocated and had complete data (modified intention to treat [mITT]) and also all those who were randomly allocated, had complete data, and received at least eight treatment sessions (per protocol [PP]). We analysed safety in the mITT population. The non-inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954. FINDINGS: Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points [SD 7·5], BA 8·4 PHQ-9 points [7·0], mean difference 0·1 PHQ-9 points [95% CI -1·3 to 1·5], p=0·89; PP: CBT 7·9 PHQ-9 points [7·3]; BA 7·8 [6·5], mean difference 0·0 PHQ-9 points [-1·5 to 1·6], p=0·99). Two (1%) non-trial-related deaths (one [1%] multidrug toxicity in the BA group and one [1%] cancer in the CBT group) and 15 depression-related, but not treatment-related, serious adverse events (three in the BA group and 12 in the CBT group) occurred in three [2%] participants in the BA group (two [1%] patients who overdosed and one [1%] who self-harmed) and eight (4%) participants in the CBT group (seven [4%] who overdosed and one [1%] who self-harmed). INTERPRETATION: We found that BA, a simpler psychological treatment than CBT, can be delivered by junior mental health workers with less intensive and costly training, with no lesser effect than CBT. Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals. FUNDING: National Institute for Health Research.