Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community.

INTRODUCTION: Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine. METHODS AND ANALYSIS: This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved. ETHICS AND DISSEMINATION: Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: UTN: U1111-1294-9310, ACTRN12623000817640p.

A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression.

LEARNING OBJECTIVES: After participating in this CME activity, the psychiatrist should be better able to:• Compare and contrast therapies used in combination with transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for treating MDD. BACKGROUND: Noninvasive neuromodulation, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has emerged as a major area for treating major depressive disorder (MDD). This review has two primary aims: (1) to review the current literature on combining TMS and tDCS with other therapies, such as psychotherapy and psychopharmacological interventions, and (2) to discuss the efficacy, feasibility, limitations, and future directions of these combined treatments for MDD. METHOD: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three databases: PubMed, PsycInfo, and Cochrane Library. The last search date was December 5, 2023. RESULTS: The initial search revealed 2,519 records. After screening and full-text review, 58 studies (7 TMS plus psychotherapy, 32 TMS plus medication, 7 tDCS plus psychotherapy, 12 tDCS plus medication) were included. CONCLUSIONS: The current literature on tDCS and TMS paired with psychotherapy provides initial support for integrating mindfulness interventions with both TMS and tDCS. Adding TMS or tDCS to stable doses of ongoing medications can decrease MDD symptoms; however, benzodiazepines may interfere with TMS and tDCS response, and antipsychotics can interfere with TMS response. Pairing citalopram with TMS and sertraline with tDCS can lead to greater MDD symptom reduction compared to using these medications alone. Future studies need to enroll larger samples, include randomized controlled study designs, create more uniform protocols for combined treatment delivery, and explore mechanisms and predictors of change.

Analysis of implementation processes in a hybrid effectiveness-implementation trial of interpersonal psychotherapy (IPT) for major depressive disorder in prisons: Training, supervision, and recommendations.

BACKGROUND: There are 10 million admissions to U.S. prisons and jails each year. More than half of those admitted have mental health problems. The goal of this article is to inform: (1) implementation of evidence-based mental health treatments in prisons and jails, an important effort that needs more evidence to guide it; (2) psychotherapy and interpersonal psychotherapy (IPT) training efforts, especially in low-resource settings. METHODS: A randomized hybrid effectiveness-implementation trial of group IPT for major depressive disorder (MDD) in state prisons found that IPT increased rates of MDD remission and lowered posttraumatic stress disorder symptoms relative to prison treatment as usual. The trial used prison counselors, only some of whom had prior psychotherapy training/experience, to deliver IPT. IPT treatment adherence was high (96%), but trial training and supervision were too costly to be scalable outside the trial. The current article reports results from a planned qualitative analysis of 460 structured implementation and supervision documents in that trial to describe training and supervision processes and lessons learned, inform training recommendations, and facilitate future work to optimize training and supervision for under-resourced settings. RESULTS: Themes identified in implementation and supervision process notes reflected: work on psychotherapy basics (reflective listening, focusing on emotions, open-ended questions, specific experiences), IPT case conceptualization (forming a conceptualization, what is and is not therapeutic work, structure and limit setting, structure vs. flexibility), IPT techniques (enhancing social support, role plays, communication analysis), psychotherapy processes (alliance repair, managing group processes), and managing difficult situations (avoidance, specific clients, challenging work settings). Counselors were receptive to feedback; some relied on study supervisors for support in managing stressful prison working conditions. CONCLUSIONS: Findings can be used to make future training and supervision more efficient. Based on our results, we recommend that initial and refresher training focus on IPT case conceptualization, steps for addressing each IPT problem area, and reflective listening. We also recommend supervision through at least counselors' first two rounds of groups. More low-cost, scalable training methods are needed to get mental health treatment to individuals who need it most, who are often served in challenging, low-resource settings such as prisons. This is a mental health access and equity issue. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01685294).

Effects of repetitive transcranial magnetic stimulation on individual variability of resting-state functional connectivity in major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment. METHODS: Variability in rs-fc was examined in healthy controls (baseline) and individuals with MDD (baseline and after 4-6 weeks of rTMS). Seed-based connectivity was calculated to 4 regions associated with MDD: left dorsolateral prefrontal cortex (DLPFC), right subgenual anterior cingulate cortex (sgACC), bilateral insula, and bilateral precuneus. Individual variability was quantified for each region by calculating the mean correlational distance of connectivity maps relative to the healthy controls; a higher variability score indicated a more atypical/idiosyncratic connectivity pattern. RESULTS: We included data from 66 healthy controls and 252 individuals with MDD in our analyses. Patients with MDD did not show significant differences in baseline variability of rs-fc compared with controls. Treatment with rTMS increased rs-fc variability from the right sgACC and precuneus, but the increased variability was not associated with clinical outcomes. Interestingly, higher baseline variability of the right sgACC was significantly associated with less clinical improvement (p = 0.037, uncorrected; did not survive false discovery rate correction).Limitations: The linear model was constructed separately for each region of interest. CONCLUSION: This was, to our knowledge, the first study to examine individual variability of rs-fc related to rTMS in individuals with MDD. In contrast to our hypotheses, we found that rTMS increased the individual variability of rs-fc. Our results suggest that individual variability of the right sgACC and bilateral precuneus connectivity may be a potential mechanism of rTMS.

Interventions promoting recovery from depression for patients transitioning from outpatient mental health services to primary care: A scoping review.

INTRODUCTION: Major Depressive Disorder (MDD) is one of the most prevalent mental disorders worldwide with significant personal and public health consequences. After an episode of MDD, the likelihood of relapse is high. Therefore, there is a need for interventions that prevent relapse of depression when outpatient mental health care treatment has ended. This scoping review aimed to systematically map the evidence and identify knowledge gaps in interventions that aimed to promote recovery from MDD for patients transitioning from outpatient mental health services to primary care. MATERIALS AND METHODS: We followed the guidance by Joanna Briggs Institute in tandem with the PRISMA extension for Scoping Reviews checklist. Four electronic databases were systematically searched using controlled index-or thesaurus terms and free text terms, as well as backward and forward citation tracking of included studies. The search strategy was based on the identification of any type of intervention, whether simple, multicomponent, or complex. Three authors independently screened for eligibility and extracted data. RESULTS: 18 studies were included for review. The studies had high heterogeneity in design, methods, sample size, recovery rating scales, and type of interventions. All studies used several elements in their interventions; however, the majority used cognitive behavioural therapy conducted in outpatient mental health services. No studies addressed the transitioning phase from outpatient mental health services to primary care. Most studies included patients during their outpatient mental health care treatment of MDD. CONCLUSIONS: We identified several knowledge gaps. Recovery interventions for patients with MDD transitioning from outpatient mental health services to primary care are understudied. No studies addressed interventions in this transitioning phase or the patient's experience of the transitioning process. Research is needed to bridge this gap, both regarding interventions for patients transitioning from secondary to primary care, and patients' and health care professionals' experiences of the interventions and of what promotes recovery. REGISTRATION: A protocol was prepared in advance and registered in Open Science Framework (https://osf.io/ah3sv), published in the medRxiv server (https://doi.org/10.1101/2022.10.06.22280499) and in PLOS ONE (https://doi.org/10.1371/journal.pone.0291559).

A Fully Remote Randomized Trial of Transcranial Alternating Current Stimulation for the Acute Treatment of Major Depressive Disorder.

Objective: Major depressive disorder (MDD) is common, but current treatment options have significant limitations in terms of access and efficacy. This study examined the effectiveness of transcranial alternating current stimulation (tACS) for the acute treatment of MDD.Methods: We performed a triple-blind, fully remote, randomized controlled trial comparing tACS with sham treatment. Adults aged 21-65 years meeting DSM 5 criteria for MDD and having a score on the Beck Depression Inventory, Second Edition (BDI-II), between 20 and 63 were eligible to participate. Participants utilized tACS or sham treatment for two 20-minute treatment sessions daily for 4 weeks. The primary outcome was change in BDI-II score from baseline to the week 2 time point in an intent-to treat analysis, followed by analyses of treatment-adherent participants. Secondary analyses examined change at the week 1 and 4 time points, responder rates, subgroup analyses, other self-report mood measures, and safety. The study was conducted from April to October 2022.Results: A total of 255 participants were randomized to active or sham treatment. Improvement in intent-to-treat analysis was not statistically significant at week 2 (P= .056), but there were significant effects in participants with high adherence (P= .005). Significantly greater improvement at week 1 (P= .020) and greater response at week 4 (P= .028) occurred following tACS. Improvements were significantly larger for female participants. There were no significant effects on secondary mood measures. Side effects were minimal and mild.Conclusions: Rapid, clinically significant improvement in depression in adults with MDD was associated with tACS, particularly for women. Compared to other depression therapies, tACS has 3 key advantages: rapid, clinically significant treatment effect, the ability of patients to use the treatment on their own at home, and the rarity and low impact of adverse events.Trial Registration: ClinicalTrials.gov identifier: NCT05384041.

Treatment resistant late-life depression: A narrative review of psychosocial risk factors, non-pharmacological interventions, and the role of clinical phenotyping.

BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. LIMITATIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.

Brain stimulation over the left DLPFC enhances motivation for effortful rewards in patients with major depressive disorder.

BACKGROUND: Amotivation is a typical feature in major depressive disorder (MDD), which produces reduced willingness to exert effort. The dorsolateral prefrontal cortex (DLPFC) is a crucial structure in goal-directed actions and therefore is a potential target in modulating effortful motivation. However, it remains unclear whether the intervention is effective for patients with MDD. METHODS: We employed transcranial magnetic stimulation (TMS), computational modelling and event-related potentials (ERPs) to reveal the causal relationship between the left DLPFC and motivation for effortful rewards in MDD. Fifty patients underwent both active and sham TMS sessions, each followed by performing an Effort-Expenditure for Rewards Task, during which participants chose and implemented between low-effort/low-reward and high-effort/high-reward options. RESULTS: The patients showed increased willingness to exert effort for rewards during the DLPFC facilitated session, compared with the sham session. They also had a trend in larger P3 amplitude for motivated attention toward chosen options, larger CNV during preparing for effort exertion, and larger SPN during anticipating a high reward. Besides, while behavior indexes for effortful choices were negatively related to depression severity in the sham session, this correlation was weakened in the active stimulation session. CONCLUSIONS: These findings provide behavioral, computational, and neural evidence for the left DLPFC on effortful motivation for rewards. Facilitated DLPFC improves motor preparation and value anticipation after making decisions especially for highly effortful rewards in MDD. Facilitated DLPFC also has a potential function in enhancing motivated attention during cost-benefit trade-off. This neuromodulation effect provides a potential treatment for improving motivation in clinics.

Feasibility, Acceptability, and Preliminary Efficacy of a Smartphone App-Led Cognitive Behavioral Therapy for Depression Under Therapist Supervision: Open Trial.

BACKGROUND: Major depressive disorder affects approximately 1 in 5 adults during their lifetime and is the leading cause of disability worldwide. Yet, a minority receive adequate treatment due to person-level (eg, geographical distance to providers) and systems-level (eg, shortage of trained providers) barriers. Digital tools could improve this treatment gap by reducing the time and frequency of therapy sessions needed for effective treatment through the provision of flexible, automated support. OBJECTIVE: This study aimed to examine the feasibility, acceptability, and preliminary clinical effect of Mindset for Depression, a deployment-ready 8-week smartphone-based cognitive behavioral therapy (CBT) supported by brief teletherapy appointments with a therapist. METHODS: This 8-week, single-arm open trial tested the Mindset for Depression app when combined with 8 brief (16-25 minutes) video conferencing visits with a licensed doctoral-level CBT therapist (n=28 participants). The app offers flexible, accessible psychoeducation, CBT skills practice, and support to patients as well as clinician guidance to promote sustained engagement, monitor safety, and tailor treatment to individual patient needs. To increase accessibility and thus generalizability, all study procedures were conducted remotely. Feasibility and acceptability were assessed via attrition, patient expectations and feedback, and treatment utilization. The primary clinical outcome measure was the clinician-rated Hamilton Depression Rating Scale, administered at pretreatment, midpoint, and posttreatment. Secondary measures of functional impairment and quality of life as well as maintenance of gains (3-month follow-up) were also collected. RESULTS: Treatment credibility (week 4), expectancy (week 4), and satisfaction (week 8) were moderate to high, and attrition was low (n=2, 7%). Participants self-reported using the app or practicing (either on or off the app) the CBT skills taught in the app for a median of 50 (IQR 30-60; week 4) or 60 (IQR 30-90; week 8) minutes per week; participants accessed the app on an average 36.8 (SD 10.0) days and completed a median of 7 of 8 (IQR 6-8) steps by the week 8 assessment. The app was rated positively across domains of engagement, functionality, aesthetics, and information. Participants' depression severity scores decreased from an average Hamilton Depression Rating Scale score indicating moderate depression (mean 19.1, SD 5.0) at baseline to a week 8 mean score indicating mild depression (mean 10.8, SD 6.1; d=1.47; P<.001). Improvement was also observed for functional impairment and quality of life. Gains were maintained at 3-month follow-up. CONCLUSIONS: The results show that Mindset for Depression is a feasible and acceptable treatment option for individuals with major depressive disorder. This smartphone-led treatment holds promise to be an efficacious, scalable, and cost-effective treatment option. The next steps include testing Mindset for Depression in a fully powered randomized controlled trial and real-world clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05386329; https://clinicaltrials.gov/study/NCT05386329?term=NCT05386329.

Managing major depressive disorder in adolescents in primary care.

ABSTRACT: Major depressive disorder (MDD) remains a significant risk to adolescent health and well-being, recently amplified by the COVID-19 pandemic. Access to adolescent mental health care services remains challenging in many areas, resulting in many adolescents diagnosed with MDD remaining untreated. Primary care providers are becoming increasingly crucial in promptly diagnosing and treating this concern. Various clinical guidelines can support clinicians in developing strategies for screening, diagnosing, and managing a vulnerable population with MDD. Standardized screenings, algorithms, and treatment guidelines can help improve the quality of life and functional impairment of those with MDD.

Family-Based Treatment for Anxiety, Depression, and ADHD for a Parent and Child.

Children with mental illness commonly live with caregivers who suffer from mental illness. Integrated mental-health-treatment approaches can provide more convenient and comprehensive care for families. This case report describes family-based treatment (FBT) for one parent/child dyad. The parent was a 37-year-old female with a history of anxiety and major depressive disorder and concern for symptoms of attention-deficit/hyperactivity disorder (ADHD). The child was an 8-year-old female with generalized anxiety disorder and concern for ADHD and behavioral problems. The parent received individual cognitive behavioral therapy (CBT) and parent management training. The child received CBT. Both also received medication management. The FBT team met regularly for coordinated treatment planning. Self-reported assessments via the Child Behavior Checklist showed meaningful improvement; anxiety decreased to nonclinical range week 12 and depression decreased to nonclinical range week 8. Clinician assessments showed improvement for both patients. Though more time intensive, FBT can yield significant improvement, particularly for children. Pragmatic approaches to treatment planning are important to minimize barriers to FBT.

Depression in Persons With Epilepsy: Lessons From Case Review.

BACKGROUND: Major depressive disorder is highly prevalent among persons with epilepsy (PWEs). Between 30% and 50% of PWEs suffer from depression. Many factors contribute to this prevalence, including the psychosocial impact of the diagnosis, restrictions on driving and certain types of work, and adverse effects associated with antiseizure medications. Without proper treatment, depressed PWEs have increased risks for suicide, strained relationships, lowered seizure control, and impairment in functioning. Our objective was to use the existing literature and insights from our experience in treating depression and anxiety in PWEs within an academic mood disorders center. We aimed to provide practical guidance for health care professionals who treat depression in this population. METHODS: Persons with epilepsy and depression were identified by their treating psychiatrists. Their electronic health records were reviewed and compiled for this report, with a total of 12 included in this review. Records were reviewed regarding antiseizure medications, psychotropic medications, light therapy, psychotherapy, other interventions, and treatment response. RESULTS: Based on our review of literature, as well as review of cases of individuals with epilepsy and comorbid psychiatric conditions, we recommend a step-wise evidence-based approach of optimizing psychiatric medication doses, augmenting with additional medication and/or implementing nonpharmacological interventions such as light therapy and psychotherapy. CONCLUSIONS: In PWEs, improvement in depression, other psychiatric symptoms, and function are the goals of drug and nondrug interventions. Depression care has the potential to significantly improve the quality of life of PWEs and reduce both morbidity and mortality.

Non-invasive vagus nerve stimulation conditions increased invigoration and wanting in depression.

BACKGROUND: Major depressive disorder (MDD) is often marked by impaired motivation and reward processing, known as anhedonia. Many patients do not respond to first-line treatments, and improvements in motivation can be slow, creating an urgent need for rapid interventions. Recently, we demonstrated that transcutaneous auricular vagus nerve stimulation (taVNS) acutely boosts effort invigoration in healthy participants, but its effects on depression remain unclear. OBJECTIVE: To assess the impact of taVNS on effort invigoration and maintenance in a sample that includes patients with MDD, evaluating the generalizability of our findings. METHODS: We used a single-blind, randomized crossover design in 30 patients with MDD and 29 matched (age, sex, and BMI) healthy control participants (HCP). RESULTS: Consistent with prior findings, taVNS increased effort invigoration for rewards in both groups during Session 1 (p = .040), particularly for less wanted rewards in HCP (pboot < 0.001). However, invigoration remained elevated in all participants, and no acute changes were observed in Session 2 (Δinvigoration = 3.3, p = .12). Crucially, throughout Session 1, we found taVNS-induced increases in effort invigoration (pboot = 0.008) and wanting (pboot = 0.010) in patients with MDD, with gains in wanting maintained across sessions (Δwanting = 0.06, p = .97). CONCLUSIONS: Our study replicates the invigorating effects of taVNS in Session 1 and reveals its generalizability to depression. Furthermore, we expand upon previous research by showing taVNS-induced conditioning effects on invigoration and wanting within Session 1 in patients that were largely sustained. While enduring motivational improvements present challenges for crossover designs, they are highly desirable in interventions and warrant further follow-up research.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

Lower odds of successful community discharge after medical hospitalization for Veterans with schizophrenia: A retrospective cohort study of national data.

Medical comorbidity, particularly cardiovascular diseases, contributes to high rates of hospital admission and early mortality in people with schizophrenia. The 30 days following hospital discharge represents a critical period for mitigating adverse outcomes. This study examined the odds of successful community discharge among Veterans with schizophrenia compared to those with major affective disorders and those without serious mental illness (SMI) after a heart failure hospital admission. Data for Veterans hospitalized for heart failure were obtained from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. Psychiatric diagnoses and medical comorbidities were assessed in the year prior to hospitalization. Successful community discharge was defined as remaining in the community without hospital readmission, death, or hospice for 30 days after hospital discharge. Logistic regression analyses adjusting for relevant factors were used to examine whether individuals with a schizophrenia diagnosis showed lower odds of successful community discharge versus both comparison groups. Out of 309,750 total Veterans in the sample, 7377 (2.4%) had schizophrenia or schizoaffective disorder and 32,472 (10.5%) had major affective disorders (bipolar disorder or recurrent major depressive disorder). Results from adjusted logistic regression analyses demonstrated significantly lower odds of successful community discharge for Veterans with schizophrenia compared to the non-SMI (Odds Ratio [OR]: 0.63; 95% Confidence Interval [CI]: 0.60, 0.66) and major affective disorders (OR: 0.65, 95%; CI: 0.62, 0.69) groups. Intervention efforts should target the transition from hospital to home in the subgroup of Veterans with schizophrenia.

The efficacy of electroconvulsive therapy in adolescent major depressive disorder with suicidal ideation: A propensity score-matched, retrospective cohort study.

BACKGROUND: More evidence is needed to validate the use of ECT in adolescent depression. This study aims to compare the effectiveness of electroconvulsive therapy (ECT) to conventional medication therapy for adolescents with major depression with suicidal ideation. METHODS: In this retrospective cohort study, we reviewed inpatient records from the First Affiliated Hospital of Chongqing Medical University spanning December 2016 to June 2021. We focused on adolescents diagnosed with severe depression presenting with suicidal tendencies. To equalize baseline differences between patients, we used the one-to-one propensity score matching to match patients who received ECT treatment with those who did not. Multivariate regression analysis was utilized to adjust for potential confounders, and subgroup analyses and sensitivity analyses were conducted to verify the robustness of our findings. RESULTS: Of the 626 patients in this study, 474 underwent ECT treatment while 152 received medication treatment, all aged between 10 and 18 years. Once matched, each group contained 143 patients. The ECT group demonstrated a significantly higher response rate and greater reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores (all P < 0.001). Additionally, the ECT group was more effective in reducing suicidal ideation, with fewer individuals retaining such ideation at discharge. In the multivariable regression analysis, both ECT treatment and shorter disease duration were independently linked to enhanced antidepressant efficacy. Subgroup analyses and sensitivity analyses verified the robustness of the main study effect. CONCLUSIONS: For adolescents with major depressive disorder and suicidal ideation, combining ECT with pharmacotherapy is more effective than pharmacotherapy alone before medications reach full effect.

Safety and efficacy of repetitive stimulation of the left dorsolateral prefrontal cortex using transcranial focused ultrasound in treatment-resistant depressed patients: A non-inferiority randomized controlled trial protocol.

BACKGROUND: About 30% of patients diagnosed with major depressive disorder fail with the mainstream pharmacological treatment. Patients who do not achieve clinical remission of symptoms, even with two different antidepressants, are classified with treatment-resistant depression (TDR). This condition imposes an additional burden with increased Disability Adjusted Life Years. Therefore, complementary treatments, such as neuromodulation, are necessary. The transcranial focused ultrasound (tFUS) has emerged in the past few years as a reliable method for non-invasive neuromodulation in humans and may help treat TRD. This study aims to propose a research protocol for a non-inferiority randomized clinical trial of TDR with tFUS. METHODS: Patients with documented TRD will be screened upon entering the TRD outpatient clinic at UFMG (Brazil). One hundred patients without a clinical history of other psychiatric illness, anatomical abnormalities on magnetic resonance imaging (MRI), or treatment with electroconvulsive therapy will be invited to participate. Patients will be randomized (1:1) into two groups: 1) treatment with a previously established protocol of transcranial magnetic stimulation; and 2) treatment with a similar protocol using the stimulation. Besides regular consultations in the outpatient clinic, both groups will attend 7 protocolled spaced days of brain stimulation targeted at the left dorsolateral prefrontal cortex. They will also be submitted to 4 sessions of image studies (2 MRIs, 2 positron-emission tomography), 3 of neuropsychological assessments (at baseline, 1 week and 2 months after treatment), the Montgomery-Åsberg Depression Rating Scale to analyze the severity of depressive symptoms. DISCUSSION: This clinical trial intends to verify the safety and clinical efficacy of tFUS stimulation of the dorsolateral prefrontal cortex of patients with TRD, compared with a previously established neuromodulation method.

The effect of the Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with major depressive disorder in Iran: a randomized controlled trial.

BACKGROUND: Depression is one of the most common mental disorders that leads to anxiety, sleep disturbances, and suicidal thoughts. Due to the high cost of treatment and the reluctance of many patients to seek medical help, major depressive disorder (MDD) is becoming more prevalent. Therefore, alternative methods like smartphone applications can help prevent and improve depression symptoms. The present study aimed to determine the effect of the newly developed Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with MDD. METHODS: This randomized controlled trial with a pretest-posttest design was conducted on Iranian patients with MDD in 2022. Sixty-four patients were recruited using convenience sampling and randomly assigned to two control and intervention groups. The intervention was conducted using the Yara smartphone application for three months. Data were collected using the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Beck Scale for Suicidal Ideation (BSSI). Data were first entered into IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA) and then analyzed using descriptive and analytical statistics. RESULTS: There was no statistically significant difference in the mean score of anxiety and sleep quality between the intervention and control groups before the intervention (p ≥ .05). However, this difference in the mean score of anxiety and sleep quality was statistically significant in the two groups after the intervention (p < .05). The results showed no statistically significant difference in the mean score of suicidal thoughts between the two groups before and after the intervention (p ≥ .05). The use of the Yara smartphone application had a significant positive effect on anxiety and sleep quality in depressed patients (p < .001). At the same time, it had no significant effect on suicidal thoughts (p ≥ .05). CONCLUSION: Considering the positive effect of using the Yara smartphone application on reducing anxiety and improving sleep quality in depressed patients, this application can help alleviate the problems of depressed patients alongside existing treatment methods. Thus, this application is recommended for this group of patients in psychiatric clinics and departments. The Yara application's effectiveness was not approved on suicidal thoughts in this study so that further investigation would be necessary. TRIAL REGISTRATION: Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N7).

Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial.

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (Mage = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (ß = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580 .

Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination.

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.