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Mind-body programs can improve mental health and well-being in military populations. This pilot study of a virtual synchronous resilience intervention was conducted from 2018 to 2020 among 26 military personnel. Participants completed self-report psychosocial questionnaires before and after the 6-week program, including measures of posttraumatic stress disorder, depression, stress, resilience, and mindfulness. The intervention included eliciting the relaxation response, adaptive coping strategies, and healthy behaviors. Pre-post changes were calculated using paired t tests and effect sizes ( d ). Significant improvements were found for depression (Patient Health Questionnaire-8), stress reactivity (Measure of Current Status-Abbreviated Scale), and mindfulness (Cognitive Affective Mindfulness Scale-Revised). A 6-week resilience intervention can help military personnel improve mental health, coping, and stress management. [ Psychiatr Ann . 2022;52(5):186–190.]

The purpose of this study was to examine differences between military veterans and service members with and without a psychiatric assistance dog (PAD) who were receiving cognitive behavioral therapy (CBT) for post-traumatic stress disorder (PTSD). Six hundred eighty-two military veterans presented at a 2-week intensive, outpatient CBT program for PTSD from February 2016 to February 2020. Self-reports of symptoms and rates of treatment completion by PAD ownership were assessed. Patients with PADs ( n = 93) reported higher scores on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( P = .04; Cohen's d = 0.23) and Neurobehavioral Symptom Inventory ( P < .01; Cohen's d = 0.34) at baseline. PTSD symptom change was comparable between participants with and without PADs ( P > .05). Dropout was higher among owners of PADs, but this difference was not significant ( P = .11). Among military populations, those with PADs may experience more severe PTSD and neuro-cognitive symptoms, but having a PAD was not associated with treatment outcome in intensive CBT. [ Psychiatr Ann . 2022;52(5):191–198.]

Military service can add stress to military-connected family members, and this stress has been linked to their overall well-being. This study examined the acceptability and explored the effectiveness of a mind-body stress management program for military-connected families and whether it was more effective delivered in person or online. Participants ( n = 55; 96% female; M age = 39.98±10.11) completed assessments of mood, functioning, mindfulness, and coping at pre- and post-program, as well as post-program qualitative feedback surveys. All participants reported that they felt comfortable during the program, and most (>90%) reported that it was helpful and would recommend it for others. Participants experienced significant improvement in stress, depressive symptoms, and self-efficacy (Cohen's d > 0.60). No significant differences in the outcomes for the in-person versus the online program were found. This program, whether delivered online or in person, seems to improve stress, self-efficacy, and depressive symptoms in military-connected families. [ Psychiatr Ann . 2022;52(5):179–185.]

Background: Childhood trauma affects the course of mood disorders. Researchers are now considering childhood trauma as an influential factor in the treatment of mood disorders. However, the role of childhood trauma in the treatment of bipolar disorder remains understudied. Methods: The effect of childhood trauma on treatment outcomes was evaluated among participants randomised to treatment with lithium or quetiapine in the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study by clinician assessment. Mixed effects linear regression models were used to analyse rates of improvement in symptom severity (assessed with the Bipolar Inventory of Symptoms Scale and the Clinical Global Impression Scale for Bipolar Disorder) and functional impairment (assessed with the Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool). Results: A history of any childhood trauma was reported by 52.7% of the sample (N = 476). Although participants with a history of any childhood trauma presented with greater symptom severity and functional impairment at most study visits, participants with and without a history of any childhood trauma showed similar rates of improvement in symptom severity and functional impairment over the 24 weeks of treatment. Conclusion: This is the first study to explore the association between childhood trauma and treatment outcomes during treatment with lithium or quetiapine in the context of a randomised trial. In Bipolar CHOICE, a history of childhood trauma did not inhibit improvement in symptom severity or functional impairment. Nevertheless, these findings need replication across different settings.

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.

Objective: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. Methods: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4–0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment. Results: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP ( N = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) ( p = 0.59). Users of Li+AC ( N = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC ( N = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p Conclusion: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic.

IntroductionThe psychological wellbeing of healthcare workers has been impacted by the high levels of stress many have experienced during the COVID-19 pandemic. This study aimed to examine the feasibility and acceptability of a brief online course focused on introducing skills that could increase resilience and decreases emotional distress in healthcare workers during the pandemic.Materials and MethodsEmployees of a large healthcare system completed a survey at baseline, one month, and two months later. The online course, called Resilience Training for Healthcare Workers, consists of three 12-20 minute videos focused on evidence-based skills that support aspects of emotional resilience: mindfulness, mentalization, and self-compassion.ResultsA total of 554 participants completed the baseline survey, endorsing moderate to high levels of emotional distress. Of those who completed all three assessments and participated in the course (n = 38), significant improvements in resilience and reductions in emotional distress were found across two months, in comparison to those who did not participate in the course.DiscussionThese findings suggest that a brief, online intervention can improve the mental health of healthcare workers during a crisis such as the COVID-19 pandemic.

Background To mitigate the psychological burdens of COVID-19 for frontline clinicians (FCs), we adapted an existing evidence-based resiliency program, Stress Management and Resilience Training Relaxation Response Program (SMART-3RP), for FCs. This analysis explores moderators of stress coping to determine which subgroups of FCs benefited most from SMART-3RP. Methods 102 FCs from Mass General Brigham hospitals engaged in the adapted SMART-3RP. Assessments were completed at group entry (Week 0) and completion (Week 4). The primary outcome was stress coping, and we examined 15 possible baseline moderators. We fit linear mixed effects regression models and assessed potential baseline moderators using a likelihood ratio test. We report model-based estimates and confidence intervals for each moderator-by-time interaction (i.e., differential effect), where positive/negative values indicate more/less improvement in average perceived stress coping. Results Stress coping improved from Week 0 to Week 4 (mean improvement [95% CI] = 0.9 [0.6 to 1.2]). FCs with higher anxiety (differential effect [95% CI] = 0.3 [0.1 to 0.4]), depression (0.4 [0.2 to 0.6]), and loneliness (0.4 [0.1 to 0.6]), but lower levels of mindfulness (CAMS-Rfocus: 1.0 [0.4 to 1.6]; CAMS-Raccept: 1.3 [0.7 to 2.0]) and self-compassion (0.4, [0.1 to 0.8]) at baseline experienced greater benefits in perceived stress coping from the SMART-3RP. Baseline health uncertainty along with sociodemographic and work characteristics did not moderate stress coping. Discussion Results highlight particular sub-populations of FCs that may benefit more from a stress management intervention, especially during emergency responses (e.g., COVID-19 pandemic).

Background Physical activity can mitigate the risk of cardiovascular diseases, but the presence of mood disorders makes it challenging to follow or develop a regular exercise habit. We conducted an online comparative effectiveness study (Healthy Hearts Healthy Minds) to evaluate whether an online psychosocial intervention adjunctive to an activity monitor (Fitbit) can improve adherence to physical activity among individuals with mood disorders who have or are at-risk for cardiovascular disease (CVD). Methods In this paper, we explore design considerations (including both procedural challenges and achievements) of relevance to our study. Results Challenges of this study included navigating a complex IRB review process, integrating two study platforms, automating study procedures, and optimizing participant engagement. Achievements of this study included building trust with collaborators, leveraging existing online communities, generating daily data reports, and conducting patient-centered research. Limitations These design considerations are based on a single online comparative effectiveness study, and other online intervention studies may be presented with other unique challenges that are specific to their study format or aims. Consistent with some of the generalizability challenges facing other online studies, participants in this study were overall highly educated (most had at least a college degree). Conclusions We successfully conducted a large-scale virtual online intervention to increase physical activity of participants with comorbid mood and cardiovascular disorders by overcoming substantial operational and technical challenges. We hope that this exploration of design considerations in the context of our online study can inform upcoming online intervention studies.

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder.

Background Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder. Methods The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response. Results Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms. Conclusions Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history.

Background Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior. Methods We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures. Results On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052= 2.9, p = 0.003 for body weight, F8,3052= 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770= 2.0, p = 0.002), BMI (F1,2767= 2.0, p = 0.002), and waist circumference (women only, F25,1621= 2.9, p Limitations Bipolar CHOICE was not designed to study anthropometric outcomes. Conclusions Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.

Objective Equine-assisted activities and therapies (EAATs) have been a growing adjunctive integrative health modality, as they allow participants to practice mindfulness, emotional regulation, and self-mastery or self-esteem building skills. Preliminary evidence suggests that these programs may be helpful in reducing posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms. The current study examines the acceptability of integrating an EAAT program as part of a two-week, intensive clinical program for veterans with PTSD and/or traumatic brain injury (TBI). Methods A family member or support person could accompany veterans and participate in the program. One hundred and six participants (veteran n = 62, family n = 44) left the urban environment in an intensive outpatient program (IOP) to attend a two-day, weekend EAAT in rural New Hampshire. Satisfaction surveys were conducted on the last day of the program and examined using thematic analysis. Results The following themes were reported in the surveys: ability of horses to catalyze emotional rehabilitation, effectiveness of immersion in equine-assisted activities, program’s ability to foster interpersonal relationships and necessity of education about PTSD for staff. Participants also reported enjoying the program as highlighted by qualitative feedback, a mean score of 9.76 (standard deviation [SD] = 0.61) as reported by veterans and a mean score of 9.91 (SD = 0.29) as reported by family members on a 10-point visual analog scale with higher scores indicating a greater overall experience. Conclusion These data offer preliminary evidence that an adjunct EAAT program is acceptable for veterans with PTSD and/or TBI participating in an IOP.

Background The ADHD Self Report Scale is a self-report measure that assesses attentional problems. We sought to validate the ASRS by establishing neural correlates using functional magnetic imaging in healthy controls and individuals with bipolar disorder (BD), who commonly exhibit attentional problems. Methods ASRS questionnaires and functional MRI data in conjunction with the Multi-source Interference Task (MSIT) were collected from 36 healthy control and 36 BD participants. We investigated task specific changes in the dorsal anterior cingulate cortex (dACC, Brodmann area 32) and their correlations with ASRS subscale scores, inattention and hyperactivity, in both cohorts. Results As hypothesized, the dACC showed significant increases in BOLD activation between the interference and noninterference conditions. For the ASRS scale as well as its Inattention and Hyperactivity subscales, there was a significant negative correlation with the dACC BOLD for the whole group. Conclusions The ASRS is sensitive to attentional difficulties in BD, suggesting that it is a valid tool for assessing attentional difficulties in patients with BD.

Depressed individuals are more likely to die from cardiovascular disease (CVD) than those without depression. People with CVD have higher rates of depression than those without and have higher mortality rates if they have comorbid depression. While physical activity (PA) improves both, few people engage in enough. We compared self-guided internet-based cognitive behavior therapy (CBT) + Fitbit or mindfulness-based cognitive therapy (MBCT) + Fitbit, with Fitbit only to increase daily steps for participants with depression who have low PA.Adult participants (N = 340) were recruited from two online patient-powered research networks and randomized to one of three study interventions for 8 weeks with an additional 8 weeks of follow-up. Using linear mixed effects models, we evaluated the effect of the intervention on average daily steps (NCT03373110).Average daily steps increased 2.8 steps per day in MBCT+Fitbit, 2.9 steps/day in CBT + Fitbit, but decreased 8.2 steps/day in Fitbit Only. These changes were not statistically different between the MBCT+Fitbit and CBT + Fitbit groups, but were different from Fitbit Only across the initial 8-week period. Group differences were not maintained across follow-up. Exploratory analyses identified comorbid anxiety disorders, self-reported PA, and employment status as moderators.Changes in daily steps over both 8- and 16-week periods-regardless of intervention group-were minimal. The results emphasize the limits of using self-guided web-based psychotherapy with an activity tracker to increase PA in participants with a history of depression and low PA.

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

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 purpose of this study was to compare standard with brief mindfulness training to improve overall well-being. METHODS Participants were recruited from 17 Patient-Powered Research Networks, online communities of stakeholders interested in a common area of research. Participants were randomized to either a standard 8-session mindfulness based cognitive therapy (MBCT) or a brief 3-session mindfulness training intervention accessed online. Participants were followed for 12 weeks. The primary outcome of the study was well-being as measured by the World Health Organization (WHO)-5 Index. We hypothesized that MBCT would be superior to brief mindfulness training. RESULTS We randomized 4,411 participants, 88% of whom were white and 80% female sex assigned at birth. Baseline WHO-5 score mean was 50.3 (SD = 20.7). Average self-reported well-being in each group increased over the intervention period (baseline to 8 weeks) (model-based slope [95% CI] for MBCT group: 0.78 [0.63, 0.93]; brief mindfulness group: 0.76 [0.60, 0.91]) as well as the full study period (i.e., intervention plus follow-up; baseline to 20 weeks) (model-based slope [95% CI] for MBCT group: 0.41 [0.34, 0.48]; brief mindfulness group: 0.33 [0.26, 0.40]). Change in self-reported well-being was not statistically significantly different between MBCT and brief mindfulness during the intervention period (model-based difference in slopes [95% CI]: -0.02 [-0.24, 0.19], P = .80) or during the intervention period plus 12-week follow-up (-0.08 [-0.18, 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, effects that were stronger for participants in the MBCT condition. CONCLUSIONS Standard MBCT improved well-being but was not superior to a brief mindfulness intervention. Younger patients and those able to complete more training sessions improved the most. CLINICALTRIAL ClinicalTrials.gov, NCT03844321, https://clinicaltrials.gov/ct2/show/NCT03844321

Using network analysis, we estimated the structure of relations among manic and depressive symptoms, respectively, in 486 patients (59% women; age: M = 37, SD = 12.1) with bipolar disorder prior to their entering a clinical trial. We computed three types of networks: (a) Gaussian graphical models (GGMs) depicting regularized partial correlations, (b) regression-based GGMs depicting nonregularized partial correlations, and (c) directed acyclic graphs (DAGs) via a Bayesian hill-climbing algorithm. Low energy and elevated energy were consistently identified as central nodes in the GGMs and as key parent nodes in the DAGs. Across analyses, pessimism about the future and depressed mood were the symptoms most strongly associated with suicidal thoughts and behavior. These exploratory analyses provide rich information about how bipolar disorder symptoms relate to one another, thereby furnishing a foundation for investigating how bipolar disorder symptoms may operate as a causal system. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background We aimed to study the probability of bipolar depression response at 24 weeks given initial non-response. Methods We combined two multi-site, 24-week trials including similar populations following the same evidence-based guidelines randomizing patients to lithium or quetiapine. Additional mood-stabilizing treatment was possible if clinically indicated. We report cumulative proportions of response (>50% improvement in MADRS) and remission (MADRS Results We included 592 participants with bipolar depression (mean 39 years, 59% female, mean MADRS 25). Among 393 (66%) participants without response after 2 weeks, 46% responded by 24 weeks; for 291 (49%) without response at 4 weeks, 40% responded and 33% remitted by 24 weeks; for 222 (38%) without a response at 6 weeks, 36% responded and 29% remitted by 24 weeks; for 185 (31%) without a response at 8 weeks, 29% responded and 24% remitted by 24 weeks. Rates were similar for participants who had started an additional mood-stabilizing drug during the first 6 or 8 weeks. Conclusions Among patients with bipolar depression and non-response after 6 weeks treatment, representing an adequate bipolar depression trial, only one-third responded by 24 weeks. These results highlight the need for better treatment alternatives for non-responders to evidence-based treatments for bipolar depression.

Individuals with bipolar disorder are at greater risk for cardiovascular disease and are less likely to adhere to lifestyle interventions than the general population. To decrease cardiovascular risk and improve adherence to lifestyle interventions, we developed the Nutrition Exercise and Wellness Treatment (NEW Tx). NEW Tx is an 18 session, 20-week cognitive behavioral therapy (CBT)-based treatment comprising 3 modules: Nutrition, Exercise, and Wellness. To evaluate the feasibility and acceptability of this intervention as well as predictors of treatment satisfaction and expectations, 38 adult outpatients with bipolar disorder were randomized to either NEW Tx or a waitlist control condition. There was no statistically significant difference in drop-out rates between the groups (26.3% in NEW Tx, 31.6% in the control condition). In the NEW Tx condition, participants attended a mean of 66.7% of sessions and reported moderate to high satisfaction. There were no study-related adverse events. We also found that expectations, but not perceived credibility (or believability), of NEW Tx (as measured by the Credibility/ Expectancy Questionnaire) at baseline predicted treatment satisfaction (as measured by the Care Satisfaction Questionnaire) post-treatment. Manic symptoms at baseline predicted treatment satisfaction, and marital status predicted one’s expectations of lifestyle interventions. Data suggest that NEW Tx is a feasible and acceptable intervention for individuals with bipolar disorder and that further research is warranted to explore potential moderators of treatment expectations and credibility in this clinical population.

Post-9/11 service members may return from military service with a complicated set of symptoms and conditions, such as posttraumatic stress disorder (PTSD), depression, substance misuse, and traumatic brain injury (TBI), that interfere with reintegration and impair functioning. Although evidence-based treatments that facilitate recovery exist, their successful delivery at a sufficient dose is limited. Barriers to accessing treatment combined with challenges compiling a comprehensive treatment team further delay delivery of effective evidence-based care for PTSD, TBI, and co-occurring mental health conditions. This paper describes the development of a comprehensive, multidisciplinary, 2-week intensive day program for post-9/11 veterans with complex mental health concerns. The treatment program combines skill building groups, family education, and integrative health approaches with evidence-based individual PTSD or TBI care. Initial results from the first 132 participants were notable for a 97% completion rate, as well as statistically significant and clinically meaningful reductions in PTSD, neurobehavioral, and depression symptom severity for the 107 veterans who completed the PTSD track and the 21 who completed the TBI track. These data suggest the intensive program approach is an effective, well-tolerated model of treatment for post-9/11 veterans with PTSD and/or TBI. Future controlled studies should examine the effectiveness of this intensive model compared to standard evidence-based therapy delivery, as well as longitudinal outcomes.

Mindfulness-based interventions (MBIs) for depression have become a frequent focus of research and clinical practice in recent decades. This article summarizes evidence regarding the use of MBIs in the prevention of depressive episodes and relief of depressive symptoms across different phases of depression. Much of the review is focused on evidence for mindfulness-based cognitive therapy (MBCT), a widely studied MBI for depression. There is strong evidence for MBCT in preventing depressive relapse among people with recurrent depression in remission. The evidence is less robust and consistent with respect to MBCT as a treatment for acute depression and treatment refractory depression. For some populations of people who are depressed, particularly those who prefer alternatives to antidepressant medications, MBIs may provide an adjunctive treatment option. Emerging work on MBIs suggests that online and other mobile health strategies may be used in the future. [ Psychiatr Ann. 2019;49(1):16–20.]

Depression is the leading cause of global disability, and many patients fail to respond to standard treatments. Preliminary evidence suggests that adjunctive nutrition therapy may improve treatment outcomes in depression. We review the evidence for the efficacy and/or mechanisms of the following nutrients: vitamin D, vitamins B12 and B9, vitamin C, zinc, selenium, omega-3 fatty acid, N-acetylcysteine, and nicotinamide riboside. Preliminary evidence suggests that these nutrients may facilitate mood regulation by regulating neurotransmitters, engaging in reduction-oxidation, or by modulating neuronal structure. Although initial evidence is promising, large, placebo-controlled studies are needed to validate their efficacy. [ Psychiatr Ann. 2019;49(1):21–25.]

Background In real-world pragmatic administrative databases, patient reported remission is often missing. Objective We evaluate if, in administrative data, five features of antidepressant use patterns can replace patient-reported symptom remission. Method We re-examined data from Sequence Treatment Alternatives to Relieve Depression (STAR*D) study. Remission was measured using 50% reduction in Hamilton index. Pattern of antidepressant use was examined through five variables: (a) number of prior ineffective antidepressants, (b) duration of taking current antidepressant, (c) receiving therapeutic dose of the medication, and (d) switching to another medication, or (e) augmenting with another antidepressant. The likelihood ratio (LR) associated with each of these predictors was assessed in 90% of data (3329 cases) and evaluated in 10% of data (350 cases) set-aside for evaluation. The accuracy of predictions was calculated using Area under the Receiver Operating Curve (AROC). Results Patients who took antidepressants for 14 weeks (LR = 2.007) were more likely to have symptom remission. Prior use of 3 antidepressants reduced the odds of remission (LR = 0.771). Patients who received antidepressants below therapeutic dose were 5 times less likely to experience remission (LR = 0.204). Antidepressant that were augment or switched, almost never led to remission (LR = 0.008, LR = 0.002 respectively). Patterns of antidepressant use accurately (AROC = 0.93) predicted symptom remission. Conclusion Within the first 100 days, antidepressants use patterns could serve as a surrogate measure for patient-reported remission of symptoms.

Background: Adjunctive antidepressants are frequently used for bipolar depression but their clinical efficacy has been studied in few trials and little is known about how co-occurring manic symptoms affect treatment response. Methods: Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (N = 482) and Lithium Treatment Moderate-Dose Use Study (N = 281) were similar comparative effectiveness trials on outpatients with bipolar disorder comparing four different randomized treatment arms with adjunctive personalized guideline-based treatment for 24 weeks. Adjunctive antidepressant treatment could be used if clinically indicated and was assessed at every study visit. Adjusted mixed effects linear regression analyses compared users of antidepressants to nonusers overall and in different subcohorts. Results: Of the 763 patients, 282 (37.0%) used antidepressant drugs during the study. Antidepressant users had less improvement compared to nonusers on the Clinical Global Impression Scale for Bipolar Disorder and on measures of depression. This was particularly true among patients with co-occurring manic symptoms. Exclusion of individuals begun on antidepressants late in the study (potentially due to overall worse response) resulted in no differences between users and nonusers. We found no differences in treatment effects on mania scales. Conclusions: In this large cohort of outpatients with bipolar disorder, clinically indicated and guideline-based adjunctive antidepressant treatment was not associated with lower depressive symptoms or higher mania symptoms. The treatment-by-indication confounding due to the nonrandomized design of the trials complicates causal interpretations, but no analyses indicated better treatment effects of adjunctive antidepressants.

Introduction Veterans involved in the justice system are an understudied population warranting attention given their higher risk of mental health concerns and psychosocial challenges. Thus, there is a need for programs to support the psychological health of incarcerated veterans. The present study sought to determine the acceptability and effectiveness of a mind-body stress reduction program for incarcerated veterans. Materials and Methods Twenty-four incarcerated veterans (100% male; Mage = 44.87 (SD = 13.84)) completed a 6 week mind-body stress reduction course, or Resilient Warrior. Participants completed validated, self-report assessments of mood, functioning, mindfulness, and coping at pre- and post-program as well as having post-program qualitative feedback surveys. Results Results showed improvement in depressive symptom severity, self-efficacy, and resilience over the study duration (P Conclusions The Resilient Warrior program is acceptable and well-tolerated for incarcerated veterans as well as may improve aspects of psychological health. Future studies could examine how stress reductions program might improve recidivism rates and quality of life after the release of incarcerated veterans.

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) (β=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.

Bipolar disorder is a debilitating mental health condition marked by episodes of mania or hypomania and depression. A person with bipolar disorder cycles between these mood episodes throughout his or her lifetime, leading to significant impairment in functioning and overall quality of life. Sleep disturbances pervade the course of bipolar disorder, occurring before, during, and after mood episodes. Sleep disturbances also negatively impact the treatment outcome for individuals with bipolar disorder. Thus, interventions aimed at improving sleep in this clinical population are needed. This chapter discusses sleep disturbances in the context of bipolar disorder as well as empirically validated strategies to improve sleep specifically for bipolar disorder.

Author(s): Goldstein, Benjamin I; Baune, Bernhard T; Bond, David J; Chen, Pao-Huan; Eyler, Lisa; Fagiolini, Andrea; Gomes, Fabiano; Hajek, Tomas; Hatch, Jessica; McElroy, Susan L; McIntyre, Roger S; Prieto, Miguel; Sylvia, Louisa G; Tsai, Shang-Ying; Kcomt, Andrew; Fiedorowicz, Jess G | Abstract: ObjectivesThe association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular-bipolar link remains underrecognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment.MethodsAn international group of experts completed a selective review of the literature, distilling core themes, identifying limitations and gaps in the literature, and highlighting future directions to bridge these gaps.ResultsThe association between bipolar disorder and vascular disease is large in magnitude, consistent across studies, and independent of confounding variables where assessed. The vascular-bipolar link is multifactorial and is difficult to study given the latency between the onset of bipolar disorder, often in adolescence or early adulthood, and subsequent vascular disease, which usually occurs decades later. As a result, studies have often focused on risk factors for vascular disease or intermediate phenotypes, such as structural and functional vascular imaging measures. There is interest in identifying the most relevant mediators of this relationship, including lifestyle (eg, smoking, diet, exercise), medications, and systemic biological mediators (eg, inflammation). Nonetheless, there is a paucity of treatment studies that deliberately engage these mediators, and thus far no treatment studies have focused on engaging vascular imaging targets.ConclusionsFurther research focused on the vascular-bipolar link holds promise for gleaning insights regarding the underlying causes of bipolar disorder, identifying novel treatment approaches, and mitigating disparities in cardiovascular outcomes for people with bipolar disorder.

Objectives: Given that veterans are significantly more likely to suffer from post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), depression, and anxiety than civilians, yet current...

Background Successful medication management for bipolar disorder requires clinicians to monitor and adjust regimens as needed, to achieve maximum effectiveness and patient adherence. This study aims to measure the prevalence of indications for medication adjustment at visits for bipolar disorder treatment; the frequency with which physicians recommend medication adjustments; and how strongly the indications predict the adjustments. Methods Data included 3,094 visits for 457 patients in Bipolar CHOICE, a comparative effectiveness study that compared treatment with lithium versus quetiapine. A set of indications for adjustment was matched to reports of whether the physician recommended a medication adjustment at that visit, and what type. Associations between indication and adjustment were examined using bivariate tests and hierarchical logistic mixed effects models. Results Medication adjustment was recommended at 63% of the visits where one of the indications was present, and at 53% of all visits. In multivariable analyses, adjustment was more likely to be recommended if there was an indication of non-response or side effects, for patients who started on quetiapine rather than lithium, or for patients who were female, married, employed or more educated. Limitations The study's cross-sectional design implies that observed associations could result from confounding variables. Also, the CHOICE trial placed certain restrictions on physicians’ medication choices, although this is not likely to have resulted in major alterations of prescribing patterns. Conclusions Clinical inertia may help explain the lack of any adjustment recommendation at 37% of the visits where one of the indications was present. Other explanations could also apply, such as watchful waiting.

Research has often been viewed as a passive process by which participants enroll in studies developed by researchers. It is becoming clearer that to understand the nuances of mood episodes and how to prevent them, we need to conduct large clinical trials that have the power to investigate moderators and mediators, or catalysts and mechanisms of change. MoodNetwork, the first online, patient-centered research community for individuals with mood disorders, aims to change the way that traditional research has been conducted by involving patients, their caregivers, and advocates in the process of research. The aim of this report is to share lessons learned from developing MoodNetwork.Participants enroll by completing a demographic survey and consent form. Once enrolled, participants are encouraged to complete optional surveys about their mood disorders and areas of research priority. Stakeholder and advocacy partners developed the website, web-based surveys, and recruitment materials.MoodNetwork has enrolled 4103 participants to date. Of this sample, 96.9% report experiencing depression and 79.7% endorse symptoms of mania or hypomania. Participants rated reducing stigma and alleviating symptoms as their 2 largest research priorities. Recruitment has been slower than expected. Recruiting a diverse sample has been challenging, and this impacts the Network's ability to conduct comparative effectiveness research studies.We discuss lessons learned from recruiting individuals with mood disorders to MoodNetwork, an innovative approach to conducting clinical trials. We identify and review 5 strategies for increasing enrollment as well as future directions.

There are over one million post-9/11 military caregivers in the United States who face a variety of stressors inherent to caring for an incapacitated loved one. Mind-body interventions, such as the Stress Management and Resilience Training Relaxation Response Resiliency Program (SMART-3RP), have been shown to reduce stress and improve overall health and functioning. The present qualitative study aims to explore stressors experienced by military caregivers in their caregiving role and to assess attitudes towards the virtual delivery of the SMART-3RP. We conducted two focus groups with a total of 13 caregivers [M (SD) age = 41.25 (11.49); 92% female], and participants subsequently completed a survey on their caregiving experiences. Focus groups were conducted remotely via Google Hangouts by two doctoral-level clinicians, transcribed verbatim, and coded using inductive thematic analysis. Themes related to stressors of caregiving included: logistical stressors faced by caregivers, demands of the caregiving role, concerns about children, worries about the future, exacerbation of the caregiver's physical/mental health concerns, social dynamics, sacrifices made for their veteran in the caregiving role, and relationship dynamics between the veteran and caregiver. Military caregivers found the SMART-3RP logical and felt as though it could be helpful to them. Caregivers expressed interest in a brief, virtual version of the SMART-3RP. Using the findings from the current study, we are adapting the SMART-3RP to be administered virtually as a podcast-based intervention.

Objective: Up to 60% of patients with bipolar disorder develop a substance use disorder during their lifetime. The purpose of this paper was to assess the impact of substance use disorders on depression recovery among bipolar patients randomly assigned to different psychotropic medications and psychosocial interventions. We hypothesized that patients with a comorbid substance use disorder would benefit less from psychotherapy regardless of treatment intensity/length compared to patients without a comorbid substance use disorder. Method: We conducted post hoc analyses among bipolar disorder patients ( n = 270) with and without comorbid substance use disorders enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder randomized psychosocial intervention trial. All patients entered during or shortly after the onset of a bipolar depressive episode. Logistic regression and Cox proportional hazard models were used to assess whether current or past substance use disorders moderated the response of patients to intensive psychosocial intervention or brief psychoeducation with collaborative care, operationalized as full recovery from an episode of bipolar depression. Results: Current comorbid substance use disorders significantly predicted likelihood of recovery (odds ratio = 2.25, p = 0.025) and time to recovery (odds ratio = 1.71, p = 0.006) from bipolar depression. We found that 74.5% of patients with a current substance use disorder, compared to 56.5% without a current substance use disorder, recovered from bipolar depression. Past substance use disorders did not predict likelihood of recovery or time to recovery. Current substance use disorders did not significantly moderate response to intensive psychotherapy versus collaborative care. Conclusion: Contrary to our hypotheses, bipolar disorder participants with a current comorbid substance use disorder were more likely to recover from psychosocial treatment for bipolar depression than patients without a current comorbid substance use disorder. If this finding is replicated, it has implications for the ordering of treatment for patients with comorbid bipolar disorder and substance use disorders.

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti-triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials.

Background and objectives Substance use disorders (SUDs) are present in up to 70% of patients with bipolar disorder (BD) and contribute to high rates of disability, morbidity, and treatment non-adherence. Despite this prevalence, few trials have investigated targeted psychosocial interventions for comorbid BD and SUDs. Methods Using PubMed and PsycINFO, we conducted a search of the literature up to January 2018 for psychosocial interventions targeted to patients with comorbid BD and SUDs. We identified eight total trials. Of these studies, four randomized and two open trials targeted the types of substance use (alcohol and illicit drugs) of primary concern to mood stability; the remaining two studies, both open trials, targeted smoking cessation. Results None of the randomized trials provided consistent evidence for management of both mood symptoms and substance use though integrated group therapy (IGT) demonstrated consistent beneficial effects on substance use outcomes. Other treatments showed benefit for mood symptoms without benefits for alcohol or illicit substance use. Small pilot studies of combined treatments for smoking cessation provided some initial promise. Conclusions At present, IGT is the most-well validated and efficacious approach if substance use is targeted in an initial treatment phase. For a subsequent phase, additional psychosocial BD treatments may be needed for mood and functioning benefits. Scientific significance This review synthesizes the psychosocial interventions that have been conducted in comorbid BD and SUDs while also providing a perspective on which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. (Am J Addict 2018;27:188-201).

BACKGROUND The impact of psychosis on the treatment of bipolar depression is remarkably understudied. The primary aim of this study was to compare treatment outcomes of bipolar depressed individuals with and without psychosis. The secondary aim was to compare the effect of lithium and quetiapine, each with adjunctive personalized treatments (APTs), in the psychotic subgroup. METHODS We assessed participants with DSM-IV bipolar depression included in a comparative effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS) and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP). Mixed models were used to assess the course of symptom change, and Cox regression survival analysis was used to assess the time to remission. RESULTS Psychotic features were present in 10.6% (n = 32) of the depressed participants (n = 303). Those with psychotic features had higher scores on the BISS before (75.2 ± 17.6 vs. 54.9 ± 16.3; P

Background Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium. Methods The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18–70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes. Results 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38–0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03). Limitations Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure. Conclusions Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions.