Pilot Study of a Brief Sleep Intervention for Suicidal Ideation in Bipolar Disorder.

OBJECTIVE: We investigated the feasibility and acceptability of a brief sleep intervention and sleep monitoring device in bipolar disorder (BD), as well as the intervention's effectiveness in reducing suicidal ideation through improved sleep quality and duration. METHODS: Participants (N=13) with BD received 4 sessions of cognitive-behavioral therapy for sleep disturbance and completed assessments of the intervention and sleep device acceptability, mood, suicidal ideation, and sleep at pretreatment and posttreatment. RESULTS: Feasibility and acceptability of the intervention were high at both pretreatment and posttreatment and did not significantly change by the intervention's conclusion, although participants reported being significantly more likely to recommend the intervention to others at posttreatment. The sleep device was easy to understand, wear, and did not interfere with participants' sleep. Suicidal ideation and depressive symptoms significantly decreased from pretreatment to posttreatment (P<0.05). There were small, but not significant, improvements in the percentage of time spent in stable sleep and total average nightly sleep. CONCLUSION: The potential of this intervention for reducing suicidal ideation and improving sleep is promising, but future research is warranted.

Electroencephalographic Biomarkers for Treatment Response Prediction in Major Depressive Illness: A Meta-Analysis.

OBJECTIVE: Reducing unsuccessful treatment trials could improve depression treatment. Quantitative EEG (QEEG) may predict treatment response and is being commercially marketed for this purpose. The authors sought to quantify the reliability of QEEG for response prediction in depressive illness and to identify methodological limitations of the available evidence. METHOD: The authors conducted a meta-analysis of diagnostic accuracy for QEEG in depressive illness, based on articles published between January 2000 and November 2017. The review included all articles that used QEEG to predict response during a major depressive episode, regardless of patient population, treatment, or QEEG marker. The primary meta-analytic outcome was the accuracy for predicting response to depression treatment, expressed as sensitivity, specificity, and the logarithm of the diagnostic odds ratio. Raters also judged each article on indicators of good research practice. RESULTS: In 76 articles reporting 81 biomarkers, the meta-analytic estimates showed a sensitivity of 0.72 (95% CI=0.67-0.76) and a specificity of 0.68 (95% CI=0.63-0.73). The logarithm of the diagnostic odds ratio was 1.89 (95% CI=1.56-2.21), and the area under the receiver operator curve was 0.76 (95% CI=0.71-0.80). No specific QEEG biomarker or specific treatment showed greater predictive power than the all-studies estimate in a meta-regression. Funnel plot analysis suggested substantial publication bias. Most studies did not use ideal practices. CONCLUSIONS: QEEG does not appear to be clinically reliable for predicting depression treatment response, as the literature is limited by underreporting of negative results, a lack of out-of-sample validation, and insufficient direct replication of previous findings. Until these limitations are remedied, QEEG is not recommended for guiding selection of psychiatric treatment.

MoodNetwork: An Innovative Approach to Patient-centered Research.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Bipolar mixed features - Results from the comparative effectiveness for bipolar disorder (Bipolar CHOICE) study.

BACKGROUND: DSM-5 changed the criteria from DSM-IV for mixed features in mood disorder episodes to include non-overlapping symptoms of depression and hypomania/mania. It is unknown if, by changing these criteria, the same group would qualify for mixed features. We assessed how those meeting DSM-5 criteria for mixed features compare to those meeting DSM-IV criteria. METHODS: We analyzed data from 482 adult bipolar patients in Bipolar CHOICE, a randomized comparative effectiveness trial. Bipolar diagnoses were confirmed through the MINI International Neuropsychiatric Interview (MINI). Presence and severity of mood symptoms were collected with the Bipolar Inventory of Symptoms Scale (BISS) and linked to DSM-5 and DSM-IV mixed features criteria. Baseline demographics and clinical variables were compared between mood episode groups using ANOVA for continuous variables and chi-square tests for categorical variables. RESULTS: At baseline, the frequency of DSM-IV mixed episodes diagnoses obtained with the MINI was 17% and with the BISS was 20%. Using DSM-5 criteria, 9% of participants met criteria for hypomania/mania with mixed features and 12% met criteria for a depressive episode with mixed features. Symptom severity was also associated with increased mixed features with a high rate of mixed features in patients with mania/hypomania (63.8%) relative to those with depression (8.0%). LIMITATIONS: Data on mixed features were collected at baseline only and thus do not reflect potential patterns in mixed features within this sample across the study duration. CONCLUSIONS: The DSM-5 narrower, non-overlapping definition of mixed episodes resulted in fewer patients who met mixed criteria compared to DSM-IV.

Poor quality of life and functioning in bipolar disorder.

BACKGROUND: This study explores the association of demographic and clinical features with quality of life and functioning in individuals with bipolar disorder. METHODS: Adult participants (N = 482) with bipolar I or II disorder were enrolled in a comparative effectiveness study across eleven study sites and completed baseline measures of medical and psychiatric history, current mood, quality of life, and functioning. Participants with at least mildly depressive or manic/hypomanic symptomatic severity were randomized to receive lithium or quetiapine in addition to adjunctive personalized treatment for 6 months. RESULTS: Participants with more severe depressive and irritability symptoms had lower quality of life and higher functional impairment. All psychiatric comorbid conditions except substance use disorder were associated with worse quality of life. On average, females had lower quality of life than males. Patients who were married, living as married, divorced, or separated had worse functional impairment compared with patients who were single or never married. A composite score of social disadvantage was associated with worse functioning and marginally associated with worse quality of life. Symptom severity did not moderate the effect of social disadvantage on quality of life or functioning. CONCLUSIONS: Our findings highlight that depression, irritability, and psychiatric comorbid conditions negatively impact quality of life and functioning in bipolar disorder. The study suggests that individuals with social disadvantage are at risk for functional impairment. Trial Registration This study is registered with ClinicalTrials.gov. Identification number: NCT01331304.

L-Methylfolate For Bipolar I depressive episodes: An open trial proof-of-concept registry.

BACKGROUND: L-methylfolate is a compelling candidate to treat bipolar I major depressive episodes. While approved as an adjunct for unipolar major depressive disorder, no studies have been done to assess the tolerability, safety, and efficacy of L-methylfolate for bipolar depression. As a first step, we developed a registry of bipolar patients treated with L-methylfolate to examine tolerability and outcomes. METHODS: Subjects (N=10) received treatment as usual plus daily L-methylfolate 15mg for 6 weeks in this open-label registry. Depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and manic symptoms with the Young Mania Rating Scale (YMRS). Effect size was measured with Cohen's d to provide an estimate of potential efficacy. RESULTS: The pre-treatment mean (SD) MADRS score was 23.4 (4.34); the post-treatment score was 13.9 (8.24). Cohen's d was 1.19. At post-treatment, 6/10 patients had at least 50% MADRS improvement, and 4/10 patients exhibited remission with MADRS≤10. The pre-treatment YMRS score was 3.2 (3.0); the post-treatment score was 2.7 (5.2). Cohen's d was 0.17. LIMITATIONS: This registry was a small open-label clinical trial for a fluctuating disorder. We cannot rule out that our results are due to regression to the mean. A controlled trial is warranted. CONCLUSIONS: This first proof-of-concept open registry suggests that L-methylfolate in combination with treatment as usual has potential to treat bipolar depression.

Cognitive Remediation and Bias Modification Strategies in Mood and Anxiety Disorders.

PURPOSE OF REVIEW: Cognitive impairments and biases, which are prevalent in patients with mood and anxiety disorders, can affect quality of life and functioning. Traditional treatments are only insufficiently addressing these impairments and biases. We review the cognitive impairments and biases present in these disorders as well as treatments targeting these domains. RECENT FINDINGS: Interventions aimed at improving cognitive impairments and biases may help improve cognitive deficits and overall functioning in patients with mood and anxiety disorders. Direct comparisons of treatments for cognitive impairments or biases versus more traditional psychosocial interventions have produced diverse results. SUMMARY: Overall, treatments for cognitive impairments and cognitive biases warrant additional study in clinical trials. Future research should explore cognitive remediation and cognitive bias modification adjunctive to psychosocial treatments to optimize patient outcomes in mood and anxiety disorders.