The genetics of severe depression.

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have recently achieved extremely large sample sizes and yielded substantial numbers of genome-wide significant loci. Because of the approach to ascertainment and assessment in many of these studies, some of these loci appear to be associated with dysphoria rather than with MDD, potentially decreasing the clinical relevance of the findings. An alternative approach to MDD GWAS is to focus on the most severe forms of MDD, with the hope that this will enrich for loci of larger effect, rendering their identification plausible, and providing potentially more clinically actionable findings. Here we review the genetics of severe depression by using clinical markers of severity including: age of onset, recurrence, degree of impairment, and treatment with ECT. There is evidence for increased family-based and Single Nucleotide Polymorphism (SNP)-based estimates of heritability in recurrent and early-onset illness as well as severe functional impariment. GWAS have been performed looking at severe forms of MDD and a few genome-wide loci have been identified. Several whole exome sequencing studies have also been performed, identifying associated rare variants. Although these findings have not yet been rigorously replicated, the elevated heritability seen in severe MDD phenotypes suggests the value of pursuing additional genome-wide interrogation of samples from this population. The challenge now is generating a cohort of adequate size with consistent phenotyping that will allow for careful and robust classifications and distinctions to be made. We are currently pursuing such a strategy in our 50-site worldwide Gen-ECT-ics consortium.

Clinical Interviewing: An Essential but Neglected Method of Medicine.

Clinical interviewing is the basic method to understand how a person feels and what are the presenting complaints, obtain medical history, evaluate personal attitudes and behavior related to health and disease, give the patient information about diagnosis, prognosis, and treatment, and establish a bond between patient and physician that is crucial for shared decision making and self-management. However, the value of this basic skill is threatened by time pressures and emphasis on technology. Current health care trends privilege expensive tests and procedures and tag the time devoted to interaction with the patient as lacking cost-effectiveness. Instead, the time spent to inquire about problems and life setting may actually help to avoid further testing, procedures, and referrals. Moreover, the dialogue between patient and physician is an essential instrument to increase patient's motivation to engage in healthy behavior. The aim of this paper was to provide an overview of clinical interviewing and its optimal use in relation to style, flow and hypothesis testing, clinical domains, modifications according to settings and goals, and teaching. This review points to the primacy of interviewing in the clinical process. The quality of interviewing determines the quality of data that are collected and, eventually, of assessment and treatment. Thus, interviewing deserves more attention in educational training and more space in clinical encounters than it is currently receiving.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

Effect of Computer-Assisted Cognitive Behavior Therapy vs Usual Care on Depression Among Adults in Primary Care: A Randomized Clinical Trial.

Importance: Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression. Objectives: To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment. Design, Setting, and Participants: This randomized clinical trial included adult primary care patients from clinical practices at the University of Louisville who scored 10 or greater on the Patient Health Questionnaire-9 (PHQ-9) and were randomly assigned to CCBT or TAU for 12 weeks of active treatment. Follow-up assessments were conducted 3 and 6 months after treatment completion. Enrollment occurred from June 24, 2016, to May 13, 2019. The last follow-up assessment was conducted on January 30, 2020. Interventions: CCBT included use of the 9-lesson computer program Good Days Ahead, along with as many as 12 weekly telephonic support sessions of approximately 20 minutes with a master's level therapist, in addition to TAU, which consisted of the standard clinical management procedures at the primary care sites. TAU was uncontrolled, but use of antidepressants and psychotherapy other than CCBT was recorded. Main Outcomes and Measures: The primary outcome measure (PHQ-9) and secondary outcome measures (Automatic Thoughts Questionnaire for negative cognitions, Generalized Anxiety Disorder-7, and the Satisfaction with Life Scale for quality of life) were administered at baseline, 12 weeks, and 3 and 6 months after treatment completion. Satisfaction with treatment was assessed with the Client Satisfaction Questionnaire-8. Results: The sample of 175 patients was predominately female (147 of 174 [84.5%]) and had a high proportion of individuals who identified as racial and ethnic minority groups (African American, 44 of 162 patients who reported [27.2%]; American Indian or Alaska Native, 2 [1.2%]; Hispanic, 4 [2.5%]; multiracial, 14 [8.6%]). An annual income of less than $30 000 was reported by 88 of 143 patients (61.5%). Overall, 95 patients (54.3%) were randomly assigned to CCBT and 80 (45.7%) to TAU. Dropout rates were 22.1% for CCBT (21 patients) and 30.0% for TAU (24 patients). An intent-to-treat analysis found that CCBT led to significantly greater improvement in PHQ-9 scores than TAU at posttreatment (mean difference, -2.5; 95% CI, -4.5 to -0.8; P = .005) and 3 month (mean difference, -2.3; 95% CI, -4.5 to -0.8; P = .006) and 6 month (mean difference, -3.2; 95% CI, -4.5 to -0.8; P = .007) follow-up points. Posttreatment response and remission rates were also significantly higher for CCBT (response, 58.4% [95% CI, 46.4-70.4%]; remission, 27.3% [95% CI, 16.4%-38.2%]) than TAU (response, 33.1% [95% CI, 20.7%-45.5%]; remission, 12.0% [95% CI, 3.3%- 20.7%]). Conclusions and Relevance: In this randomized clinical trial, CCBT was found to have significantly greater effects on depressive symptoms than TAU in primary care patients with depression. Because the study population included people with lower income and lack of internet access who typically have been underrepresented or not included in earlier investigations of CCBT, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings. Additional studies with larger samples are needed to address implementation procedures that could enhance the effectiveness of CCBT and to examine potential factors associated with treatment outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02700009.

Computer-Assisted CBT and Mobile Apps for Depression: Assessment and Integration Into Clinical Care.

A surge in the development of computer-assisted cognitive-behavioral therapy (CCBT) and mobile apps for depression has provided many tools with potential for enhancing treatment delivery. This article assesses progress in evaluation and implementation of CCBT and mobile apps for depression, with a focus on providing practical information on clinical applications. Advantage and disadvantages of these technologies are identified, outcome research is reviewed, and recommendations are made for clinical use. With increasing use of computer technology in everyday life, it is likely that clinicians and patients will pursue opportunities to employ computer tools in treatment for depression.

Improving Cost-effectiveness and Access to Cognitive Behavior Therapy for Depression: Providing Remote-Ready, Computer-Assisted Psychotherapy in Times of Crisis and Beyond.

INTRODUCTION: There is growing evidence that computer-delivered or computer-assisted forms of cognitive behavior therapy (CCBT) are helpful, but cost-effectiveness versus standard therapies is not well established. OBJECTIVE: To evaluate the cost-effectiveness of a therapist-supported method for CCBT in comparison to standard cognitive behavior therapy (CBT). METHODS: A total of 154 drug-free major depressive disorder outpatients were randomly assigned to either 16 weeks of standard CBT (up to twenty 50-min sessions) or CCBT using the Good Days Ahead program (including up to 5.5 h of therapist contact). Outcomes were assessed at baseline, weeks 8 and 16, and at 3 and 6 months post-treatment. Economic analyses took into account the costs of services received and work/social role impairment. RESULTS: In the context of almost identical efficacy, a form of CCBT that used only about one third the amount of therapist contact as conventional CBT was highly cost-effective compared to conventional therapy and reduced the adjusted cost of treatment by USD 945 per patient. CONCLUSIONS: A method of CCBT that blended internet-delivered modules and abbreviated therapeutic contact reduced the cost of treatment substantially without adversely affecting outcomes. Results suggest that use of this approach can more than double the access to CBT. Because clinician support in CCBT can be provided by telephone, videoconference, and/or email, this highly efficient form of treatment could be a major advance in remote treatment delivery.

Development of the National Network of Depression Centers Mood Outcomes Program: A Multisite Platform for Measurement-Based Care.

OBJECTIVES: Mood disorders are among the most burdensome public health concerns. The National Network of Depression Centers (NNDC) is a nonprofit consortium of 26 leading clinical and academic member centers in the United States providing care for patients with mood disorders, including depression and bipolar disorder. The NNDC has established a measurement-based care program called the Mood Outcomes Program whereby participating sites follow a standard protocol to electronically collect patient-reported outcome assessments on depression, anxiety, and suicidal ideation in routine clinical care. This article describes the approaches taken to develop and implement the program. METHODS: Since 2015, eight pilot sites have implemented the program and followed more than 10,000 patients. This pilot study presents descriptive statistics based on the first 24-month period of data collection. RESULTS: In this sample, 58.6% of patients with bipolar disorder (N=849) and 57.5% of patients with unipolar depression (N=3,998) remained symptomatic at follow-up. Lifetime rates of planned or actual suicide attempts were high, ranging from 27.6% for patients with unipolar mood disorders to 33.5% for patients with bipolar disorder. Men, unmarried individuals, and those with comorbid anxiety had a poorer longitudinal course. This initial snapshot of clinical burden is consistent with public health data indicating that mood disorders are severely debilitating. CONCLUSIONS: This study demonstrates the potential of the Mood Outcomes Program to create a nationwide "learning health system" for mood disorders. This goal will be further realized as the program expands in reach and scope across additional NNDC sites.

Computer-Assisted Cognitive-Behavior Therapy and Mobile Apps for Depression and Anxiety.

PURPOSE OF REVIEW: We reviewed research on computer-assisted cognitive-behavior therapy (CCBT) and mobile applications with the goals of assessing the effectiveness of these newer methods of delivering or augmenting treatment and making recommendations on the clinical use of computer tools in psychotherapy of depression and anxiety. RECENT FINDINGS: Research on CCBT has found solid evidence for efficacy when the use of a therapeutic computer program is supported by a clinician or other helping professionals. Lower levels of efficacy or ineffectiveness typically have been found when computer programs are used as stand-alone treatments. A large number of mobile apps have been created that claim to be useful for depression and/or anxiety. However, considerable caution is warranted in evaluating mobile apps and recommending them to patients. Research on mobile apps is still in an early stage of development. A number of well-established CCBT programs have been studied in multiple randomized, controlled trials and have been found to be effective. Such programs appear to have adequate quality, security, and efficacy to be used in clinical practice. Mobile apps offer easy portability and immediate access to coping strategies and may be useful for augmenting treatment. But clinicians need to select apps with integrity and reliable content for clinical use.

Computer-Assisted Cognitive-Behavior Therapy for Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy of computer-assisted forms of cognitive-behavior therapy for major depressive disorder (MDD) and examine the role of clinician support and other factors that might affect outcomes. DATA SOURCES: Ovid MEDLINE, PsycINFO, PubMed, and Scopus from their beginnings to July 18, 2016. Keywords were "randomized, controlled trials of computer-assisted cognitive-behavior therapy for depression" and "randomized, controlled trials of mobile apps for cognitive-behavior therapy of depression." STUDY SELECTION: Of 223 studies identified in the search, 183 were excluded yielding a sample of 40 randomized, controlled investigations of computer-assisted cognitive-behavior therapy (CCBT) for depression. DATA EXTRACTION: Data were abstracted independently by two authors, and consensus was reached by discussion with a third author. RESULTS: The overall mean effect size for CCBT compared to control conditions was g = 0.502, a moderately large effect. Studies that provided support from a clinician or other person yielded significantly larger effects (g = 0.673) than studies in which no support was provided (g = 0.239). Completion rate and study setting also influenced outcomes. Lower mean effect sizes were observed in studies with lower completion rates and in studies conducted in primary care practices. CONCLUSIONS: CCBT with a modest amount of support from a clinician or other helping person was found to be efficacious with relatively large mean effect sizes on measures of depressive symptoms. Self-guided CCBT for depression was considerably less effective. Future research should focus on enhancing the implementation of CCBT, including evaluating the amount and type of support needed for effective delivery, methods to improve engagement with computer-assisted therapies, and ways to improve treatment outcome in primary care settings.

Dissemination of computer-assisted cognitive-behavior therapy for depression in primary care.

Computer-assisted cognitive-behavior therapy (CCBT) for depression in primary care will be evaluated in a trial with 240 patients randomly assigned to CCBT or treatment as usual (TAU). The study will disseminate a therapy method found to be effective in psychiatric settings into primary care - a setting in which there have been significant problems in the delivery of adequate, evidence-based treatment for depression. The study will include a high percentage of disadvantaged (low-income) patients - a population that has been largely ignored in previous research in CCBT. There have been no previous studies of CCBT for depression in primary care that have enrolled large numbers of disadvantaged patients. The form of CCBT used in this study is designed to increase access to effective therapy, provide a cost-effective method, and be a sustainable model for wide-spread use in primary care. In order to deliver therapy in a practical manner that can be replicated in other primary care practices, patients with significant symptoms of depression will receive treatment with an empirically supported computer program that builds cognitive-behavior therapy skills. Support for CCBT will be provided by telephone and/or e-mail contact with a care coordinator (CC) instead of face-to-face treatment with a cognitive-behavior therapist. Outcome will be assessed by measuring CCBT completion rate, comprehension of CBT concepts, and satisfaction with treatment, in addition to ratings of depressive symptoms, negative thoughts, and quality of life. The cost-effectiveness analysis and exploration of possible predictors of outcome should help clinicians, health care organizations, and others plan further dissemination of CCBT in primary care.

Computer-Assisted Cognitive-Behavior Therapy in Medical Care Settings.

PURPOSE OF REVIEW: We reviewed research on computer-assisted cognitive-behavior therapy (CCBT) performed in medical settings with the goals of assessing the effectiveness of this newer method of treatment delivery, evaluating the need for clinician support of therapeutic computer programs, and making suggestions for future research and clinical implementation. RECENT FINDINGS: The overall results of randomized, controlled trials suggest that CCBT can be an effective treatment for depression in primary care patients and health care anxiety. Also, it can be a useful component of treatment for somatic conditions including irritable bowel syndrome, diabetes, fibromyalgia, and chronic pain. The amount and type of clinician support needed for maximizing effectiveness remains unclear. CCBT offers promise for overcoming barriers to delivering effective psychotherapy in medical settings. We recommend that next steps for researchers include more definitive studies of the influence of clinician support, investigations focused on implementation in clinical practices, cost-benefit analyses, and use of technological advances.

Methodological Recommendations for Trials of Psychological Interventions.

Recent years have seen major developments in psychotherapy research that suggest the need to address critical methodological issues. These recommendations, developed by an international group of researchers, do not replace those for randomized controlled trials, but rather supplement strategies that need to be taken into account when considering psychological treatments. The limitations of traditional taxonomy and assessment methods are outlined, with suggestions for consideration of staging methods. Active psychotherapy control groups are recommended, and adaptive and dismantling study designs offer important opportunities. The treatments that are used, and particularly their specific ingredients, need to be described in detail for both the experimental and the control groups. Assessment should be performed blind before and after treatment and at long-term follow-up. A combination of observer- and self-rated measures is recommended. Side effects of psychotherapy should be evaluated using appropriate methods. Finally, the number of participants who deteriorate after treatment should be noted according to the methods that were used to define response or remission.

Computer-Assisted Cognitive-Behavior Therapy for Depression in Primary Care: Systematic Review and Meta-Analysis.

OBJECTIVE: To examine evidence for the effectiveness of computer-assisted cognitive-behavior therapy (CCBT) for depression in primary care and assess the impact of therapist-supported CCBT versus self-guided CCBT. METHODS: A search for randomized studies of CCBT compared to control groups for treating depression in primary care settings was conducted using Ovid MEDLINE, PsycINFO, PubMed, and Scopus. We extracted the following information from the studies that met inclusion criteria: mean depression rating scale scores before and after treatment, number of patients, type of control group and CCBT program, therapist support time and method of support, and treatment completion rate. Meta-analyses compared differences between posttreatment mean scores in each condition, as well as mean scores at follow-up. Study quality and possible bias also were assessed. RESULTS: Eight studies of CCBT for depression in primary care met inclusion criteria. The overall effect size was g = 0.258, indicating a small but significant advantage for CCBT over control conditions. Therapist support was provided in 4 of the 8 studies. The effect size for therapist-supported CCBT was g = 0.372-a moderate effect. However, the effect size for self-guided CCBT was g = 0.038, indicating little effect. CONCLUSIONS: Implementation of therapist-supported CCBT in primary care settings could enhance treatment efficiency, reduce cost, and improve access to effective treatment for depression. However, evidence to date suggests that self-guided CCBT offers no benefits over usual primary care.

Improving the Efficiency of Psychotherapy for Depression: Computer-Assisted Versus Standard CBT.

OBJECTIVE: The authors evaluated the efficacy and durability of a therapist-supported method for computer-assisted cognitive-behavioral therapy (CCBT) in comparison to standard cognitive-behavioral therapy (CBT). METHOD: A total of 154 medication-free patients with major depressive disorder seeking treatment at two university clinics were randomly assigned to either 16 weeks of standard CBT (up to 20 sessions of 50 minutes each) or CCBT using the "Good Days Ahead" program. The amount of therapist time in CCBT was planned to be about one-third that in CBT. Outcomes were assessed by independent raters and self-report at baseline, at weeks 8 and 16, and at posttreatment months 3 and 6. The primary test of efficacy was noninferiority on the Hamilton Depression Rating Scale at week 16. RESULTS: Approximately 80% of the participants completed the 16-week protocol (79% in the CBT group and 82% in the CCBT group). CCBT met a priori criteria for noninferiority to conventional CBT at week 16. The groups did not differ significantly on any measure of psychopathology. Remission rates were similar for the two groups (intent-to-treat rates, 41.6% for the CBT group and 42.9% for the CCBT group). Both groups maintained improvements throughout the follow-up. CONCLUSIONS: The study findings indicate that a method of CCBT that blends Internet-delivered skill-building modules with about 5 hours of therapeutic contact was noninferior to a conventional course of CBT that provided over 8 additional hours of therapist contact. Future studies should focus on dissemination and optimizing therapist support methods to maximize the public health significance of CCBT.