The Use of Text Messaging as an Adjunct to Internet-Based Cognitive Behavioral Therapy for Major Depressive Disorder in Youth: Secondary Analysis.

BACKGROUND: As an established treatment for major depressive disorder (MDD), cognitive behavioral therapy (CBT) is now implemented and assessed in internet-based formats that, when combined with smartphone apps, enable secure text messaging. As an adjunct to such internet-based CBT (ICBT) approaches, text messaging has been associated with increased adherence and therapeutic alliance. OBJECTIVE: This study analyzed data from the intervention arm of a randomized control trial evaluating 24-week ICBT for MDD (intervention arm) against standard-care psychiatry (waitlist control). The aim of this secondary analysis was to assess MDD symptom improvement in relation to the frequency and content of text messages sent by ICBT participants to Navigator-Coaches during randomized control trial participation. Higher text frequency in general and in 3 conceptual categories (appreciating alliance, alliance building disclosures, and agreement confirmation) was hypothesized to predict larger MDD symptom improvement. METHODS: Participants were young adults (18-30 years) from the Centre for Addiction and Mental Health. The frequencies of categorized texts from 20 ICBT completers were analyzed with respect to MDD symptom improvement using linear regression models. Texts were coded by 2 independent coders and categorized using content analysis. MDD symptoms were measured using the Beck Depression Inventory-II (BDI-II). RESULTS: Participants sent an average of 136 text messages. Analyses indicated that BDI-II improvement was negatively associated with text messaging frequency in general (ß=-0.029, 95% CI -0.11 to 0.048) and in each of the 3 categories: appreciating alliance (ß=-0.096, 95% CI -0.80 to 0.61), alliance building disclosures (ß=-0.098, 95% CI -0.28 to 0.084), and agreement confirmation (ß=-0.076, 95% CI -0.40 to 0.25). Altogether, the effect of text messaging on BDI-II improvement was uniformly negative across statistical models. More text messaging appeared associated with less MDD symptom improvement. CONCLUSIONS: The hypothesized positive associations between conceptually categorized text messages and MDD symptom improvement were not supported in this study. Instead, more text messaging appeared to indicate less treatment benefit. Future studies with larger samples are needed to discern the optimal use of text messaging in ICBT approaches using adjunctive modes of communication. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052.

Perceptions, Experiences, and Patterns of Cannabis Use in Individuals with Mood and Anxiety Disorders in the Context of Cannabis Legalization and Medical Cannabis Program in Canada - A Qualitative Study.

INTRODUCTION: Perceptions of cannabis as a potential medical treatment for mood and anxiety disorders have been increasing in the context of legalizations, availability, and medical cannabis programs, though current evidence predominately indicates risks and negative effects of cannabis use (CU) on mental health outcomes. This study aims to understand motivations, perceptions, effects, and patterns of CU in individuals with mood and anxiety disorders. METHODS: Thirty-six adult patients diagnosed with mood or anxiety disorders, obsessive-compulsive disorder, or posttraumatic stress disorder who were currently using cannabis completed an in-depth qualitative interview on individual motivations, perceptions, experiences, effects, and patterns of their CU. The thematic analysis focused on phases of CU and sources of cannabis products and information. RESULTS: Reported motivations for initiation of CU included curiosity, peer pressure, and dissatisfaction with conventional treatments. Factors such as psychotropic effects and coping with mental health symptoms and insomnia contributed to the continuation of CU. More negative effects, including cognitive dysfunction, worsening of mood, and anxiety symptoms, were acknowledged with ongoing CU. Concerning findings included common initiation of CU before age 18, combined medical and recreational CU, rare consultation of medical professionals on CU, and potential effects and harms. DISCUSSION: Findings indicate individual complexity of motivations, perceptions, and patterns of CU in the study population. The reported potential beneficial effects of specific cannabis products should be further investigated. Findings emphasize patient-provider dialogue on both CU and conventional treatments. Information from this study can contribute to and inform the development of education, prevention, and intervention strategies.

A randomized sham-controlled trial of high-dosage accelerated intermittent theta burst rTMS in major depression: study protocol.

BACKGROUND: Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), can be administered in 1/10th of the time of standard rTMS (~ 3 min vs. 37.5 min) yet achieves similar outcomes in depression. The brief nature of the iTBS protocol allows for the administration of multiple iTBS sessions per day, thus reducing the overall course length to days rather than weeks. This study aims to compare the efficacy and tolerability of active versus sham iTBS using an accelerated regimen in patients with treatment-resistant depression (TRD). As a secondary objective, we aim to assess the safety, tolerability, and treatment response to open-label low-frequency right-sided (1 Hz) stimulation using an accelerated regimen in those who do not respond to the initial week of treatment. METHODS: Over three years, approximately 230 outpatients at the Centre for Addiction and Mental Health and University of British Columbia Hospital, meeting diagnostic criteria for unipolar MDD, will be recruited and randomized to a triple blind sham-controlled trial. Patients will receive five consecutive days of active or sham iTBS, administered eight times daily at 1-hour intervals, with each session delivering 600 pulses of iTBS. Those who have not achieved response by the week four follow-up visit will be offered a second course of treatment, regardless of whether they initially received active or sham stimulation. DISCUSSION: Broader implementation of conventional iTBS is limited by the logistical demands of the current standard course consisting of 4-6 weeks of daily treatment. If our proposed accelerated iTBS protocol enables patients to achieve remission more rapidly, this would offer major benefits in terms of cost and capacity as well as the time required to achieve clinical response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04255784.

The Role of Daily Steps in the Treatment of Major Depressive Disorder: Secondary Analysis of a Randomized Controlled Trial of a 6-Month Internet-Based, Mindfulness-Based Cognitive Behavioral Therapy Intervention for Youth.

BACKGROUND: Current evidence supports physical activity (PA) as an adjunctive treatment for major depressive disorder (MDD). Few studies, however, have examined the relationship between objectively measured PA and MDD treatment outcomes using prospective data. OBJECTIVE: This study is a secondary analysis of data from a 24-week internet-based, mindfulness-based cognitive behavioral therapy program for MDD. The purpose of this analysis was twofold: (1) to examine average daily step counts in relation to MDD symptom improvement, and whether pain moderated this relationship; and (2) to examine whether changes in step activity (ie, step trajectories) during treatment were associated with baseline symptoms and symptom improvement. METHODS: Patients from the Centre for Addiction and Mental Health were part of a randomized controlled trial evaluating the effects of internet-based, mindfulness-based cognitive behavioral therapy for young adults (aged 18-30 years old) with MDD. Data from 20 participants who had completed the intervention were analyzed. PA, in the form of objectively measured steps, was measured using the Fitbit-HR Charge 2 (Fitbit Inc), and self-reported depression severity was measured with the Beck Depression Inventory-II (BDI-II). Linear regression analysis was used to test PA's relationship with depression improvement and the moderating effect of pain severity and pain interference. Growth curve and multivariable regression models were used to test longitudinal associations. RESULTS: Participants walked an average of 8269 steps per day, and each additional +1000-step difference between participants was significantly associated with a 2.66-point greater improvement (reduction) in BDI-II, controlling for anxiety, pain interference, and adherence to Fitbit monitoring (P=.02). Pain severity appeared to moderate (reduce) the positive effect of average daily steps on BDI-II improvement (P=.03). Higher baseline depression and anxiety symptoms predicted less positive step trajectories throughout treatment (Ps≤.001), and more positive step trajectories early in the trial predicted greater MDD improvement at the end of the trial (Ps<.04). However, step trajectories across the full duration of the trial did not significantly predict MDD improvement (Ps=.40). CONCLUSIONS: This study used objective measurements to demonstrate positive associations between PA and depression improvement in the context of cognitive behavioral treatment. Pain appeared to moderate this relationship, and baseline symptoms of anxiety and depression predicted PA trajectories. The findings inform future interventions for major depression. Future research with larger samples should consider additional moderators of PA-related treatment success and the extent to which outcomes are related to PA change in multimodal interventions. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11591.

Neural Correlates of the DEEPP (Anti-suicidal Response to Ketamine in Treatment-Resistant Bipolar Depression) Study: Protocol for a Pilot, Open-Label Clinical Trial.

BACKGROUND: Suicide is among the top 10 leading causes of death worldwide. Of people who died by suicide, the majority are diagnosed with depression. It is estimated that 25%-60% of people with bipolar depression (BD) will attempt suicide at least once, and 10%-15% will die by suicide. Several treatments, such as lithium, clozapine, electroconvulsive therapy, and cognitive behavioral therapy, have been shown to be effective in treating suicidality. However, these treatments can be difficult to tolerate or may take months to take effect. Ketamine, a glutamate N-methyl-D-aspartate antagonist, has been shown to have rapid antisuicidal effect and antidepressant qualities, and is thus a promising intervention to target acute suicidality in patients with BD. However, the biological mechanism underlying its therapeutic action remains poorly understood. Enhancing our understanding of underlying mechanisms of action for ketamine's effectiveness in reducing suicidality is critical to establishing biological markers of treatment response and developing tailored, personalized interventions for patients with BD. OBJECTIVE: This is an open-label clinical trial to test the safety and feasibility of repeated ketamine infusions to treat acute suicidality. The primary objective is to test the safety and feasibility of ketamine intervention. The secondary objective is to examine ketamine's potential neurophysiological mechanisms of action by assessing cortical excitation and inhibition to determine potential biomarkers of clinical response. Other objectives are to evaluate the effect of ketamine on acute suicidality and other clinical outcomes, such as depressive symptoms and quality of life, to inform a future larger trial. METHODS: This open-label clinical trial aims to test the safety and feasibility of repeated ketamine infusions in patients with BD for suicidality and to assess ketamine's neurophysiological effects. A sterile form of racemic ketamine hydrochloride will be administered over a 40-minute intravenous infusion 2 times per week on nonconsecutive days for 4 weeks (8 sessions). We will recruit 30 adults (24-65 year olds) over 2 years from an academic psychiatric hospital in Toronto, Canada. RESULTS: This study is currently ongoing and actively recruiting participants. So far, 5 participants have completed the trial, 1 is currently in active treatment, and 8 participants are on the waitlist to be screened. We anticipate initial results being available in the fall of 2023. This proposal was presented as a poster presentation at the Research to Reality Global Summit on Psychedelic-Assisted Therapies and Medicine, held in May 2022 in Toronto, Canada. CONCLUSIONS: Developing effective interventions for acute suicidality in high-risk populations such as those with BD remains a major therapeutic challenge. Ketamine is a promising treatment due to its rapid antidepressant and antisuicidal effects, but its underlying neurophysiological mechanisms of action remain unknown. TRIAL REGISTRATION: ClinicalTrials.gov NCT05177146; https://clinicaltrials.gov/ct2/show/NCT05177146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41013.

A qualitative exploration of the mental health challenges and therapeutic needs of Canadian correctional workers.

Purpose: Correctional work is described as a high-stress environment associated with increased prevalence of mental health disorders in employees. Identifying appropriate healthcare services necessitates investigating the mental health challenges and needs of correctional workers (CWs). Methods: Individual interviews (n = 9; 5 M and 4 W) and a mixed gender focus group (n = 6; 3 M and 3 W) were conducted to gather a general sense of the mental health landscape. Data were analyzed to develop a targeted and comprehensive question guide for gender-specific focus groups (n = 14 unique participants; 6 M and 8 W). Results: Eight themes emerged from the gender-specific focus groups. Themes focusing on work culture described the negative repercussions of job stress and the inability to discuss challenges openly due to confidentiality concerns and feelings of seclusion associated with the CW profession. Men were more likely to be subjected to physical violence and women to emotional and sexual harassment from staff and inmates. Themes related to mental health care described the benefits and limitations of the current services and digital mental healthcare. Stigma and accessibility were notable treatment barriers. Lastly, sector-specific therapy was seen as an important component in enhancing engagement and therapist interaction. Conclusion: The study demonstrates the interconnection between work culture and CW mental health that needs to be acknowledged when addressing mental health care.

Benefits of Digital Mental Health Care Interventions for Correctional Workers and Other Public Safety Personnel: A Narrative Review.

Chronic exposure to stressors and potentially psychologically traumatic events contributes to the high prevalence of mental health disorders in correctional workers (CWs) and other public safety personnel (PSP). Digital mental health interventions are an accessible and scalable method of improving and maintaining the mental health of this population. The current review explores the benefits of digital mental health interventions for PSP-with a focus on CWs-and how these innovations can address the limitations in in-person mental health care. A systematic literature search of five databases (Medline, PsycInfo, Embase, CINAHL, Google Scholar) was conducted until March 2022. The search yielded 16 publications that focused on digital mental health interventions or care available to CWs and other PSP. The benefits of digital innovations were summarized into five categories which discussed (1) their ability to enhance accessibility and reduce stigma; (2) the provision of evidence-based and structured psychotherapy programs; (3) variability in the degree of therapist engagement; (4) the integration of proactive interventions; and (5) enhancing engagement by acknowledging unique experiences and interpersonal relationships. Although digital mental health technologies for CWs are still in their infancy, there is strong evidence to support their effectiveness in ameliorating symptoms of mental distress. Future research should consider how ethnicity, gender, culture, sexual orientation, and socioeconomic status can be integrated into these therapies and how the interplay between different stakeholders and organizations can impact the effectiveness of online therapies and programs.

Correction: Comparing Online and On-Site Cognitive Behavior Therapy in Major Depressive Disorder: Protocol for a Noninferiority Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/29726.].

Comparing Online and On-Site Cognitive Behavior Therapy in Major Depressive Disorder: Protocol for a Noninferiority Randomized Controlled Trial.

BACKGROUND: The incidence of mental health disorders in Canada is increasing with costs of CAD $51 billion (US $40 billion) per year. Depression is the most prevalent cause of disability while cognitive behavioral therapy (CBT) is the best validated behavioral depression treatment. CBT, when combined with mindfulness meditation (CBT-M), has strong evidence for increased efficacy. While randomized controlled trials (RCTs) have demonstrated online CBT-M efficacy, comparisons with in-office delivery are lacking. OBJECTIVE: The aim of this research is to assess whether online group CBT-M (with standard psychiatric care) is non-inferior in efficacy and more cost-effective than office-based, on-site group CBT-M at post-intervention and 6-months follow-up in major depressive disorder. The study will also assess whether digitally recorded data (ie, online workbooks completed, Fitbit step count, and online text messages) predict depression symptom reduction in online participants. METHODS: This single-center, two-arm, noninferiority RCT employs assessor-blinded and self-report outcomes and economic evaluation. The research site is the Centre for Addiction and Mental Health (Toronto), a research-based psychiatry institution where participants will be identified from service wait lists and through contacts with other Toronto clinics. Inclusion criteria are as follows: (1) aged 18-60 years, any ethnicity; (2) Beck Depression Inventory-II (BDI-II) of mild severity (score ≥14) with no upper severity limit; (3) Mini-International Neuropsychiatric Interview-confirmed, psychiatric major depressive disorder diagnosis; (4) fluent in English. All patients are diagnosed by staff psychiatrists. Exclusion criteria are as follows: (1) receipt of weekly structured psychotherapy; (2) observation of Diagnostic and Statistical Manual of Mental Disorders (5th Edition) criteria for severe alcohol or substance use disorder (in past 3 months), borderline personality disorder, schizophrenia (or other primary psychotic disorder), bipolar disorder, or obsessive-compulsive disorder; (3) clinically significant suicidal ideation (imminent intent or attempted suicide in the past 6 months); and (4) treatment-resistant depression. All participants receive standard psychiatric care, experimental participants receive online group CBT-M, and controls receive standard care in-office group CBT-M. The online group program (in collaboration with NexJ Health, Inc) combines smartphone and computer-accessed workbooks with mental health phone counselling (16 hours in 16 weeks) that coordinates software interactions (eg, secure text messaging and Fitbit-tracked walking). The primary outcome is BDI-II, and secondary outcomes are anxiety (Beck Anxiety Inventory), depression (ie, Quick Inventory of Depressive Symptomatology and 17-item Hamilton Depression Rating Scale), mindfulness (Five-Facet Mindfulness Questionnaire), quality of life (European Quality of Life Five Dimension), and pain (Brief Pain Inventory). RESULTS: Based on prior studies with the BDI-II and 80% power to reject an inferiority hypothesis with a 1-sided type I error rate of 5%, a sample of 78 per group is adequate to detect small-to-medium-effect sizes. CONCLUSIONS: This study assesses online CBT-M efficacy and noninferiority in relation to in-person CBT, and the cost-effectiveness of both interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04825535; https://www.clinicaltrials.gov/ct2/show/NCT04825535. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29726.

Exploring women's experiences of treatment for binge eating disorder: Methylphenidate vs. cognitive behavioural therapy.

OBJECTIVE: The current qualitative study explored the personal experiences of a sample of women with binge eating disorder (BED). The women were previously enrolled in a 12-week randomized controlled trial comparing pharmacotherapy (methylphenidate [MP]) and cognitive behavioural therapy (CBT). METHODS: Semi-structured interviews were conducted with 15 women who completed the trial (8 MP, 7 CBT) to obtain their narrative accounts. Key themes were then identified from transcribed tape recordings, using thematic analysis. RESULTS: Participants described self-awareness as bringing greater attention to their binge eating, and to their thoughts and emotions. Furthermore, both groups valued the interpersonal relationships with the clinicians and their ability to create a safe and comforting environment. In the MP group, many participants described the medication as reducing their preoccupation with food, and hence, binge frequency. In CBT, there was a focus on psychoeducation and obtaining a "toolbox" of long-term binge-management skills that could also be used following treatment. In both groups, stress was described as a primary trigger for a binge and/or a cause of relapse. DISCUSSION: Although patients reported having a positive experience in the therapies, it is suggested that broader stress regulation skills training would be useful to evaluate further, to bolster relapse prevention skills. These qualitative findings add a much-needed lived-experience perspective on clinical treatments for binge eating. This is especially significant considering that a psychostimulant similar to MP is the only approved pharmacotherapy for BED, and to date, little is known about the patient's subjective experiences when taking this medication.

Vagally Mediated Heart Rate Variability Is Associated With Executive Function Changes in Patients With Treatment-Resistant Depression Following Magnetic Seizure Therapy.

OBJECTIVES: Magnetic seizure therapy (MST) is a novel investigational brain stimulation modality for patients with treatment-resistant depression (TRD). MST is a potential alternative seizure-based treatment to electroconvulsive therapy (ECT), given that it may offer equivalent antidepressant efficacy, yet with a relative sparing of cognitive functioning. Heart rate variability (HRV) is a marker of central autonomic functioning. We aimed to explore the relationships among baseline HRV, age, clinical outcome, and executive function following MST, in patients with TRD. MATERIALS AND METHODS: Eighty-eight TRD patients (55 females; 18-70 years) were enrolled and 48 patients completed a course of MST in an open-label study. Patients received MST treatments two to three times per week, using one of three stimulation frequencies (ie, 100 Hz, 50 Hz, or 25 Hz) at 100% stimulator output. Root mean square of the successive R-R differences (RMSSD), an index of HRV, was computed from a baseline electrocardiogram (ECG) recording. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D24) and the Quick Inventory of Depressive Symptomatology (QIDS16). Executive function was assessed using the Trail Making Test and the Mazes Test from the MATRICS battery. RESULTS: Baseline RMSSD was correlated with baseline HAM-D24 (r = -0.340, p = 0.001) and baseline Mazes Test (r = 0.417, p = 0.0007) but not with baseline Trail Making Test. Furthermore, baseline RMSSD was not correlated with changes on the HAM-D24, QIDS16, or total scores on the Trail Making Test. However, there was a significant correlation between baseline RMSSD and improvement on the Mazes Test following MST (r = 0.502, p = 0.0004). CONCLUSIONS: Since this is an open-label trial, the influence of the placebo effect cannot be excluded. However, our results suggest that baseline RMSSD may be a state-biomarker of depression and executive function impairment. Additionally, while baseline vagally mediated resting cardiac activity did not predict the outcome of depression, it may mediate executive function improvements following MST.

The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial.

BACKGROUND: Major depressive disorder is among the most disabling illnesses worldwide, with a lifetime prevalence of 16.2%. Research suggests that 20% to 40% of patients with depression do not respond to pharmacotherapy, developing treatment-resistant depression. Electroconvulsive therapy is the gold standard for treating individuals with treatment-resistant depression, with remission rates of approximately 75% to 90%. However, 10% to 25% of patients do not respond to electroconvulsive therapy, and many are unable to tolerate it due to the side effects. Both groups are considered to be patients who do not respond to electroconvulsive therapy, because both groups continue to exhibit symptoms of severe depression, have a limited number of treatment options available, and are in need of rapid treatment. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been shown to exert rapid antidepressant effects in patients with treatment-resistant depression when administered in subanesthetic doses through 40-minute intravenous infusions. Recently, a ketamine compound, esketamine (Spravato), that is administered through the intranasal route received regulatory approval by the US Food and Drug Administration and Health Canada to treat depression. However, esketamine is challenging to access due to high costs and limited availability. Racemic ketamine (rketamine) is cheap and easy to access; however, the effects in patients who have not responded to electroconvulsive therapy have yet to be understood or tested. This study will use transcranial magnetic stimulation to study mechanisms of human brain cortical physiology at the systemic level to identify neurobiomarkers of response. OBJECTIVE: The objective of this open-label pilot clinical trial is to test the feasibility and safety of intranasal ketamine in patients who have not responded to electroconvulsive therapy. The primary outcome is to determine the feasibility of a larger randomized controlled trial to test the efficacy of intranasal ketamine for patients who have not responded to electroconvulsive therapy for clinical indicators in unipolar depression. The secondary outcome is to determine the preliminary effects of an intervention on clinical outcomes, such as depressive symptoms, suicidal ideation, and quality of living. The third outcome is to explore neurophysiological changes as measured by transcranial magnetic stimulation electromyography and electroencephalography to measure changes in cortical excitability as potential predictors of clinical response. METHODS: A sterile solution of racemic ketamine hydrochloride will be administered twice per week for 4 weeks (8 sessions) intranasally to patients with treatment-resistant depression who did not respond to or could not tolerate an acute course of electroconvulsive therapy. We will recruit 25 adults (24-65 years old) over the course of 2 years from an academic psychiatric hospital in Toronto, Canada. RESULTS: This study has received ethics approval, and funding has been secured. The study is currently active. CONCLUSIONS: This is the first study to test repeated doses of intranasal rketamine in patients who have not responded to electroconvulsive therapy for depression. Results from this study will (1) inform the development of a larger adequately powered randomized controlled trial to test the efficacy of intranasal ketamine for depression and (2) determine potential neurophysiological markers of clinical response. TRIAL REGISTRATION: Clinical Trials.gov NCT05137938; http://clinicaltrials.gov/ct2/show/NCT05137938. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30163.

Continuation Magnetic Seizure Therapy for Treatment-Resistant Unipolar or Bipolar Depression.

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute treatment, there are no published studies of continuation MST for the prevention of relapse.Methods: Patients with TRD with a DSM-IV diagnosis of major depressive disorder or bipolar disorder who met response criteria after acute MST were offered continuation MST in a prospective, open-label trial between February 2012 and June 2019. They received 12 continuation MST sessions with decreasing frequency over the course of 6 months, with additional booster sessions if their depression symptoms started to worsen. The primary outcome was relapse of depression or psychiatric hospitalization. Secondary outcomes included relapse of suicidal ideation and neurocognitive outcomes.Results: Thirty participants completing at least one assessment during continuation MST were included in the analysis; 10 (33.3%) relapsed, with no significant differences in survival distributions between unipolar and bipolar groups (χ2 = 0.3, P = .58). Mean (SD) survival time was 18.6 (1.6) weeks. All 17 participants who achieved resolution of baseline suicidality after acute MST remained free of suicidality during the continuation phase. Except for improvement in verbal fluency, neurocognitive test scores did not change during continuation MST.Conclusions: During 6 months of continuation MST, two-thirds of participants sustained improvements in depressive symptoms without any adverse cognitive effects. Future studies of continuation MST are warranted, particularly in comparison to ECT.Trial Registration: ClinicalTrials.gov identifier: NCT01596608.

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD). Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly. OBJECTIVE: We compared the efficacy and tolerability of a twice-daily versus once-daily iTBS protocol in patients with TRD. We hypothesized that twice-daily iTBS would result in a greater improvement in depression scores compared to once-daily iTBS. METHODS: 208 participants (131 females) with TRD were randomized to receive either iTBS (600 pulses) delivered twice-daily with a 54-min interval between treatments or once-daily (1200 pulses) with 1 sham treatment with the same interval between treatments, to ensure equal levels of daily therapeutic contact and blinding of patients and raters. The primary outcome measure was change in depression scores on the Hamilton Rating Scale for Depression (HRSD-17) after 10 days of treatment and 30 days of treatments. RESULTS: HRSD-17 scores improved in both the twice-daily and once-daily iTBS groups; however, these improvements did not significantly differ between the two groups at either the 10-day or 30-day timepoints. Response and remission rates were low (<10%) in both groups after 10 days and consistent with prior reports at 30 days; these rates did not differ between the treatment groups. CONCLUSIONS: These results suggest that twice-daily iTBS does not accelerate response to iTBS and is not different from once-daily treatment in terms of improving depressive symptoms in patients with TRD. Clinicaltrials.gov ID: NCT02729792 (https://clinicaltrials.gov/ct2/show/NCT02729792).

Delivering an Online Cognitive Behavioral Therapy Program to Address Mental Health Challenges Faced by Correctional Workers and Other Public Safety Personnel: Protocol for a Mixed Methods Study.

BACKGROUND: Public safety personnel have regular and often intense exposure to potentially traumatic events at work, especially workplace violence in the case of correctional workers. Subsequently, correctional workers are at higher risk of developing mental health problems such as posttraumatic stress disorder. Public safety personnel are up to 4 times more likely to experience suicidal ideation, suicidal attempts, and death by suicide compared to the general population. Despite this high prevalence, help-seeking behaviors from public safety personnel are low due to stigma and irregular work hours limiting access to care. Innovative treatments are needed to address these challenges. OBJECTIVE: This study will investigate the efficacy of an electronically delivered cognitive behavioral therapy (e-CBT) program tailored to correctional workers' mental health problems. METHODS: This study is composed of 4 phases. In phase 1, we will interview correctional workers individually and in focus groups to identify personal, social, and cultural factors affecting their mental health and barriers to care. Phase 2 will use the information gathered from the interviews to develop gender- and diagnosis-specific e-CBT modules. These will be presented to a new group of participants who will provide further feedback on their usability and accessibility. In phase 3, we will randomly assign participants to either an e-CBT or treatment as usual arm. The program will be evaluated with validated symptomatology questionnaires and interviews. Phase 4 will use this additional information to fine-tune the e-CBT modules for a larger-scale randomized controlled trial design comparing the e-CBT program to in-person CBT. All e-CBT modules will be delivered through a secure online platform. RESULTS: The study received ethics approval in December 2020, and participant recruitment began in March 2021. Participant recruitment has been conducted through targeted advertisements and physician referrals. To date, there have been 15 participants recruited for Phase 1, and it is expected to conclude in July 2021, with phase 2 beginning in September 2021. Complete data collection and analysis from all phases are expected to conclude by July 2023. Linear and binomial regression (for continuous and categorical outcomes, respectively) will be conducted along with interpretive qualitative methods. CONCLUSIONS: If proven efficacious and feasible, this e-CBT program can provide a high-quality and clinically validated resource to address the mental health problems of correctional workers. Additionally, findings can contribute to the development of innovative treatments for other public safety professions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04666974; https://www.clinicaltrials.gov/ct2/show/NCT04666974. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30845.

Electroconvulsive therapy with a memory reactivation intervention for post-traumatic stress disorder: A randomized controlled trial.

BACKGROUND: Post-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects OBJECTIVE/HYPOTHESIS: To test the use of ECT to disrupt the reconsolidation of traumatic memories as a potential treatment for PTSD METHODS: Participants were adults from the civilian population and were referred for ECT treatment for severe depression with comorbid PTSD symptoms. Twenty-eight participants were randomly assigned to reactivation of a traumatic or non-traumatic memory using audio script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included a comparison of the change in heart rate while listening to the script RESULTS: Twenty-five female patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time CONCLUSIONS: ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT with non-traumatic memory reactivation. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04027452. IDENTIFIER: NCT04027452.

Online Mindfulness-Based Cognitive Behavioral Therapy Intervention for Youth With Major Depressive Disorders: Randomized Controlled Trial.

BACKGROUND: Approximately 70% of mental health disorders appear prior to 25 years of age and can become chronic when ineffectively treated. Individuals between 18 and 25 years old are significantly more likely to experience mental health disorders, substance dependencies, and suicidality. Treatment progress, capitalizing on the tendencies of youth to communicate online, can strategically address depressive disorders. OBJECTIVE: We performed a randomized controlled trial (RCT) that compared online mindfulness-based cognitive behavioral therapy (CBT-M) combined with standard psychiatric care to standard psychiatric care alone in youth (18-30 years old) diagnosed with major depressive disorder. METHODS: Forty-five participants were randomly assigned to CBT-M and standard care (n=22) or to standard psychiatric care alone (n=23). All participants were provided standard psychiatric care (ie, 1 session per month), while participants in the experimental group received an additional intervention consisting of the CBT-M online software program. Interaction with online workbooks was combined with navigation coaching delivered by phone and secure text messaging. RESULTS: In a two-level linear mixed-effects model intention-to-treat analysis, significant between-group differences were found for the Beck Depression Inventory-II score (difference -8.54, P=.01), Quick Inventory of Depressive Symptoms score (difference -4.94, P=.001), Beck Anxiety Inventory score (difference -11.29, P<.001), and Brief Pain Inventory score (difference -1.99, P=.03), while marginal differences were found for the Five Facet Mindfulness Questionnaire-Nonjudging subscale (difference -2.68, P=.05). CONCLUSIONS: These results confirm that youth depression can be effectively treated with online CBT-M that can be delivered with less geographic restriction. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052.

A pilot study of magnetic seizure therapy for treatment-resistant obsessive-compulsive disorder.

BACKGROUND: There is growing interest in the potential of neuromodulation options in treatment-resistant obsessive-compulsive disorder (OCD). Magnetic seizure therapy (MST), is a new treatment intervention in which generalized seizures are induced with transcranial magnetic stimulation. We conducted a pilot study to assess the efficacy and cognitive effects of MST in patients with treatment-resistant OCD. METHODS: In an open-label pilot study, participants with treatment-resistant OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores of ≥16 were treated with up to 24 acute treatments. The primary clinical outcomes were clinical response (Y-BOCS score reduction ≥30%) and remission (final Y-BOCS score ≤8). A neurocognitive battery, the Quick Inventory for Depressive Symptoms-Self Report (QIDS-SR), the Beck Scale for Suicidal Ideation (SSI), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were also completed as secondary measures. RESULTS: Ten participants with OCD who had not responded to medications or psychotherapy enrolled in the study and seven completed an adequate trial (defined as ≥8 treatments). MST was associated with minimal cognitive effects except for some decrease in autobiographical memory and no serious adverse effects. Only one participant met the predefined criteria for response, and none for remission. The baseline and endpoint Y-BOCS scores were not statistically different. CONCLUSION: Overall, MST was not beneficial in a small group of patients with treatment-resistant OCD. At this time, other studies of MST for OCD are not warranted until different coil placements targeting other brain circuits can be proposed.

Neurophysiological markers of response to theta burst stimulation in youth depression.

BACKGROUND: Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated. METHODS: Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16-24 years old). In 16 age-matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS-evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting-state functional magnetic resonance imaging (fMRI) data was also collected at baseline. RESULTS: Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC. CONCLUSIONS: TMS-probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre-treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population.