Person:

Deckersbach, Thilo

Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients’ lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D2, 5-HT2A, and 5-HT7 receptors; moderate-affinity antagonism at α2C-adrenergic receptors; low- to very low-affinity antagonism at α1A-adrenergic, α2A-adrenergic, H1, M1, and 5-HT2C receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2–3 weeks of treatment (as measured by the Montgomery–Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine–fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed.

Background: This pilot study examines the proof of concept of a consolidated Nutrition, Exercise, and Wellness Treatment (NEW Tx) for overweight individuals with bipolar disorder. Findings: Five participants completed NEW Tx, a 20-week individual cognitive behavioral therapy-based treatment comprising three modules: Nutrition teaches appropriate serving sizes and balanced diet; Exercise emphasizes increasing weekly physical activity; Wellness focuses on skills for healthy decision-making. Participants attended most sessions and reported high satisfaction with the treatment. Participants’ weight, cholesterol and trigyclerides decreased over the study duration as well as number of daily calories and sugar intake. We found that weekly exercise duration more than tripled over the study duration and depressive symptoms and functioning have improved. Conclusions: These results offer proof of concept that consolidated NEW Tx is feasible and acceptable and has the potential to improve nutrition, exercise, wellness, and mood symptoms in bipolar disorder. Future iterations of NEW Tx will reflect the strengths and lessons learned from this study.

Abstract Recent emotion dysregulation models of generalized anxiety disorder (GAD) propose chronic worry in GAD functions as a maladaptive attempt to regulate anxiety related to uncertain or unpredictable outcomes. Emotion acceptance is an adaptive emotion regulation strategy increasingly incorporated into newer cognitive behavioral therapy (CBT) approaches to GAD to counter chronic worry. The current study explores the mechanisms of emotion acceptance as an alternate emotion regulation strategy to worry or emotion suppression using functional magnetic resonance imaging. Twenty-one female participants diagnosed with GAD followed counterbalanced instructions to regulate responses to personally relevant worry statements by engaging in either emotion acceptance, worry or emotion suppression. Emotion acceptance resulted in lower ratings of distress than worry and was associated with increased dorsal anterior cingulate cortex (dACC) activation and increased ventrolateral prefrontal cortex (VLPFC)-amygdala functional connectivity. In contrast, worry showed significantly greater distress ratings than acceptance or suppression and was associated with increased precuneus, VLPFC, amygdala and hippocampal activation. Suppression did not significantly differ from acceptance in distress ratings or amygdala recruitment, but resulted in significantly greater insula and VLPFC activation and decreased VLPFC-amygdala functional connectivity. Emotion acceptance closely aligned with activation and connectivity patterns reported in studies of contextual extinction learning and mindful awareness.

Background: This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). Methods: Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. Results: For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (P<.05) on clinician- and self-rated measures of obsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n=7) satisfied full medication response criteria. Intention-to-treat analyses (n=20) showed similar improvements (P<.05) on primary and secondary study outcome measures. Conclusion: The results of this study suggest that duloxetine may provide a significant reduction in symptoms for patients with obsessive-compulsive disorder. ClinicalTrials.gov NCT00464698; http://clinicaltrials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1.

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