Web-Based Mindfulness-Based Interventions for Well-being: Randomized Comparative Effectiveness Trial.

BACKGROUND: Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being. OBJECTIVE: The primary aim of this study was to determine whether a standard 8-session web-based mindfulness-based cognitive therapy (MBCT) program, compared with a brief 3-session mindfulness intervention, improved overall participant well-being. In addition, we sought to explore whether the treatment effects differed based on the baseline characteristics of the participants (ie, moderators). METHODS: Participants were recruited from 17 patient-powered research networks, web-based communities of stakeholders interested in a common research area. Participants were randomized to either a standard 8-session MBCT or a brief 3-session mindfulness training intervention accessed on the web. The participants were followed for 12 weeks. The primary outcome of the study was well-being, as measured by the World Health Organization-Five Well-Being Index. We hypothesized that MBCT would be superior to a brief mindfulness training. RESULTS: We randomized 4411 participants, 3873 (87.80%) of whom were White and 3547 (80.41%) of female sex assigned at birth. The mean baseline World Health Organization-Five Well-Being Index score was 50.3 (SD 20.7). The average self-reported well-being in each group increased over the intervention period (baseline to 8 weeks; model-based slope for the MBCT group: 0.78, 95% CI 0.63-0.93, and brief mindfulness group: 0.76, 95% CI 0.60-0.91) as well as the full study period (ie, intervention plus follow-up; baseline to 20 weeks; model-based slope for MBCT group: 0.41, 95% CI 0.34-0.48; and brief mindfulness group: 0.33, 95% CI 0.26-0.40). Changes in self-reported well-being were not significantly different between MBCT and brief mindfulness during the intervention period (model-based difference in slopes: -0.02, 95% CI -0.24 to 0.19; P=.80) or during the intervention period plus 12-week follow-up (-0.08, 95% CI -0.18 to 0.02; P=.10). During the intervention period, younger participants (P=.05) and participants who completed a higher percentage of intervention sessions (P=.005) experienced greater improvements in well-being across both interventions, with effects that were stronger for participants in the MBCT condition. Attrition was high (ie, 2142/4411, 48.56%), which is an important limitation of this study. CONCLUSIONS: Standard MBCT improved well-being but was not superior to a brief mindfulness intervention. This finding suggests that shorter mindfulness programs could yield important benefits across the general population of individuals with various medical conditions. Younger people and participants who completed more intervention sessions reported greater improvements in well-being, an effect that was more pronounced for participants in the MBCT condition. This finding suggests that standard MBCT may be a better choice for younger people as well as treatment-adherent individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03844321; https://clinicaltrials.gov/ct2/show/NCT03844321.

Cardiometabolic risk markers during mood-stabilizing treatment: Correlation with drug-specific effects, depressive symptoms and treatment response.

BACKGROUND: Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response. METHODS: We analyzed data from two similar 24-weeks comparative effectiveness trials, with a combined sample of 770 participants randomized to two different lithium doses, quetiapine (300 mg/day), or standard treatment without lithium. Glucose, lipids and vital signs were measured before and after 24 weeks of treatment. We calculated several cardiovascular risk scores, assessed baseline correlations and compared the four treatment arms via multiple linear regression models. RESULTS: Higher cholesterol and LDL levels were associated with greater depression severity, showing differential correlations to specific symptoms, particularly agitation, low energy and suicidality. Those randomized to quetiapine showed a significant worsening of cardiometabolic markers during the 24-week trial. Neither baseline nor change in lipid levels correlated with differential treatment response. LIMITATIONS: Study duration was short from the perspective of cardiometabolic risk markers, and all treatment arms included patients taking adjunct antipsychotics. The trials compared quetiapine to lithium, but not to other medications known to affect similar risk factors. CONCLUSIONS: Treatment with 300 mg/day quetiapine for 24 weeks, representing a short and common dose course, resulted in increased cardiometabolic risk markers, emphasizing the importance of monitoring during mood-stabilizing treatment. The symptom-specific associations are in line with previous studies in unipolar depression, suggesting a cardiometabolic-depression link that needs to be further studied in bipolar depression.

Targeting Mitochondrial Dysfunction for Bipolar Disorder.

People with bipolar disorder (BD) all too often have suboptimal long-term outcomes with existing treatment options. They experience relapsing episodes of depression and mania and also have interepisodic mood and anxiety symptoms. We need to have a better understanding of the pathophysiology of BD if we are to make progress in improving these outcomes. This chapter will focus on the critical role of mitochondria in human functioning, oxidative stress, and the biological mechanisms of mitochondria in BD. Additionally, this chapter will present the evidence that, at least for some people, BD is a product of mitochondrial dysregulation. We review the modulators of mitochondria, the connection between current BD medication treatments and mitochondria, and additional medications that have theoretical potential to treat BD.

Psychotic symptoms during bipolar depressive episodes and suicidal ideation.

BACKGROUND: Psychotic symptoms during bipolar depressive episodes, especially in outpatients, are under recognized and studied by clinicians and researchers. We examined the relationship between psychotic symptoms during a depressive episode and suicidal ideation in bipolar patients. METHODS: Participants (N = 351) were adult, depressed outpatients with bipolar disorder (BD) in a comparative effectiveness study of quetiapine versus lithium. Psychotic symptoms were assessed via Bipolar Inventory of Signs and Symptoms Scale (BISS) and depressive episodes via Mini-International Neuropsychiatric Interview (MINI). Because only 4.84% (N = 17) endorsed psychotic symptoms, we performed iterative multivariate matching with non-psychotic participants. On every matched population, a multiple regression analysis examined whether psychotic symptoms were associated with suicidal ideation, via the Concise Health Risk Taking scale (CHRT-12). RESULTS: Averaged across the 50 matched populations, current psychotic symptoms predicted active suicidal ideation on the CHRT, but not a passive propensity toward suicide or total CHRT scores, after adjusting for common correlates of suicidality (e.g., previous suicidal behavior) (ß=0.59, p=.01, R2= 0.41). LIMITATIONS: Our study was limited by three factors. First, the generalizability of our study was limited as the sample included only outpatients. Next, the analysis was cross-sectional and does not allow for causal interpretation. Lastly, our study lacked information regarding the content and mood congruency of participants' psychosis. CONCLUSION: While a small proportion of BD outpatients had current symptoms of psychosis during their depressive episode, those who did were more likely to endorse active suicidal thoughts, including suicide methods and plans.