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.

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.

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.

Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: an open-label clinical trial

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov

Magnetic seizure therapy (MST) for major depressive disorder.

Electroconvulsive therapy (ECT) is effective for major depressive disorder (MDD) but its effects on memory limit its widespread use. Magnetic seizure therapy (MST) is a potential alternative to ECT that may not adversely affect memory. In the current trial, consecutive patients with MDD consented to receive MST applied over the prefrontal cortex according to an open-label protocol. Depressive symptoms and cognition were assessed prior to, during and at the end of treatment. Patients were treated two to three times per week with high-frequency MST (i.e., 100 Hz) (N = 24), medium frequency MST (i.e., 60 or 50 Hz) (N = 26), or low-frequency MST (i.e., 25 Hz MST) (N = 36) using 100% stimulator output. One hundred and forty patients were screened; 86 patients with MDD received a minimum of eight treatments and were deemed to have an adequate course of MST; and 47 completed the trial per protocol, either achieving remission (i.e., 24-item Hamilton Rating Scale for Depression score <10 and a relative reduction of >60% at two consecutive assessments; n = 17) or received a maximum of 24 sessions (n = 30). High-frequency (100 Hz) MST produced the highest remission rate (33.3%). Performance on most cognitive measures remained stable, with the exception of significantly worsened recall consistency of autobiographical information and significantly improved brief visuospatial memory task performance. Under open conditions, MST led to clinically meaningful reduction in depressive symptoms in patients with MDD and produced minimal cognitive impairment. Future studies should compare MST and ECT under double-blind randomized condition.

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

BACKGROUND: About 70% of all mental health disorders appear before the age of 25 years. When untreated, these disorders can become long-standing and impair multiple life domains. When compared with all Canadian youth (of different ages), individuals aged between 15 and 25 years are significantly more likely to experience mental health disorders, substance dependencies, and risks for suicidal ideation and death by suicide. Progress in the treatment of youth, capitalizing on their online responsivity, can strategically address depressive disorders. OBJECTIVE: We will conduct a randomized controlled trial to compare online mindfulness-oriented cognitive behavioral therapy (CBT-M) combined with standard psychiatric care versus psychiatric care alone in youth diagnosed with major depressive disorder. We will enroll 168 subjects in the age range of 18 to 30 years; 50% of subjects will be from First Nations (FN) backgrounds, whereas the other 50% will be from all other ethnic backgrounds. There will be equal stratification into 2 intervention groups (INT1 and INT2) and 2 wait-list control groups (CTL1 and CTL2) with 42 subjects per group, resulting in an equal number of INT1 and CTL1 of FN background and INT2 and CTL2 of non-FN background. METHODS: The inclusion criteria are: (1) age 18 to 30 years, FN background or other ethnicity; (2) Beck Depression Inventory (BDI)-II of at least mild severity (BDI-II score ≥14) and no upper limit; (3) Mini-International Neuropsychiatric Interview (MINI)-confirmed psychiatric diagnosis of major depressive disorder; and (4) fluent in English. All patients are diagnosed by a Centre for Addiction and Mental Health psychiatrist, with diagnoses confirmed using the MINI interview. The exclusion criteria are: (1) individuals receiving weekly structured psychotherapy; (2) individuals who meet the Diagnostic and Statistical Manual of Mental Disorders criteria for severe alcohol/substance use disorder in the past 3 months, or who demonstrate clinically significant suicidal ideation defined as imminent intent, or who have attempted suicide in the past 6 months; and (3) individuals with comorbid diagnoses of borderline personality, schizophrenia, bipolar disorder, and/or obsessive compulsive disorder. All subjects are provided standard psychiatric care defined as 1 monthly session that focuses on appropriate medication, with session durations of 15 to 30 min. Experimental subjects receive an additional intervention consisting of the CBT-M online software program (in collaboration with Nex J Health, Inc). Exposure to and interaction with the online workbooks are combined with navigation-coaching delivered by phone and secure text message interactions. RESULTS: The outcomes selected, combined with measurement blinding, are key features in assessing whether significant benefits regarding depression and anxiety symptoms occur. CONCLUSIONS: If results confirm the hypothesis that youth can be effectively treated with online CBT-M, effective services may be widely delivered with less geographic restriction. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11591.

A randomized comparison of long acting methylphenidate and cognitive behavioral therapy in the treatment of binge eating disorder.

Cognitive behavioral therapy (CBT) is a well-established treatment for binge eating disorder (BED); however, this treatment is underutilized, highlighting the need for additional treatment alternatives. Dopamine neurotransmission has been associated with dysregulated eating, and pharmaceutical agents targeting the dopamine system are associated with decreased binge eating and weight. The primary objective of the current investigation was to evaluate the efficacy of psychostimulant medication versus current best practices in the treatment of BED symptoms, in a randomized trial of methylphenidate versus CBT for BED. The secondary objective was to evaluate the ability of impulsivity to predict treatment outcomes. Female outpatients with BED were randomized to receive methylphenidate (n = 22) or CBT (n = 27) for 12 weeks. The primary outcome was objective binge episode frequency; secondary outcomes included subjective binge episode frequency, body mass index (BMI), BED symptoms, and quality of life. Results showed that both treatments had a significant impact on primary and secondary outcomes. Methylphenidate and CBT were associated with decreases in subjective and objective binge episodes; methylphenidate was associated with greater decreases in BMI. Two impulsivity traits predicted clinical outcomes. Results provide preliminary support for the therapeutic benefit of methylphenidate in BED treatment, and prognostic utility of impulsivity in this context.

Characteristics of ictal EEG in Magnetic Seizure Therapy at various stimulation frequencies.

OBJECTIVES: The first objective of this study aimed to elucidate the relationship between seizure characteristics and Magnetic Seizure Therapy (MST) treatment outcome. The second objective was to determine the effect of stimulation frequency on seizure characteristics. METHODS: Using a between-subjects design, we compared the seizures of patients with unipolar depression receiving MST at three separate stimulation frequencies: 25 Hz (n = 34), 50 Hz (n = 16) and 100 Hz (n = 11). Seizures were rated for overall seizure adequacy on a scale of 0-6, with one point given for each measure that was considered to be adequate according to the ECT literature: (1) seizure EEG duration (2) motor duration, (3) post-ictal suppression, (4) ictal EEG maximum amplitude, (5) Global Seizure Strength, and (6) Symmetry. Mixed-effect models were used to evaluate the effect of frequency on seizure characteristics and the relationships between seizure characteristics and clinical outcome. RESULTS: (1) 100 Hz induced seizures that were less adequate than seizures induced with 50 Hz and 25 Hz stimulations. Seizures induced by 50 Hz stimulations had longer slow-wave phase durations and total EEG durations than the 100 Hz and 25 Hz groups. Global seizure strength was less robust in seizures induced by 100 Hz MST compared to the other stimulation frequencies. (2) Shorter polyspike durations and smaller slow-wave amplitude predicted reductions in overall symptoms of depression as measured by the 24-item Hamilton Depression Scale. CONCLUSION: Analysis of our first objective revealed stimulation frequency significantly influences measures of overall seizure adequacy. However, our results also revealed these descriptions of seizure adequacy based on ECT literature may not be useful for MST-induced seizures, as the characteristics of MST-induced seizure characteristics may predict clinical response in a different manner. SIGNIFICANCE: These results may help to distinguish the biological processes impacted by stimulation frequency and may suggest different mechanisms of action between convulsive therapies and challenge the current understanding of seizure adequacy for MST.