Aims and Results of the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
CNS Neuroscience & Therapeutics (Impact Factor: 3.93). 06/2011; 18(3):243-9. DOI: 10.1111/j.1755-5949.2011.00257.x
Source: PubMed

ABSTRACT The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP-BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP-BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP-BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP-BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders.

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Available from: Vivek Singh, Sep 02, 2014
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    • "Bipolar disorder (BPD) represents a group of common, disabling conditions of mood dysregulation. The improved ability to control overt illness symptoms through psychopharmacological and psychosocial treatments, as highlighted in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study [1], has afforded new opportunities for people with mental illness. However, studies suggest that functional and psychological well-being of individuals with bipolar disorders is not consistently predicted by symptom severity [2,3]. "
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    ABSTRACT: Bipolar disorder (BPD) is a common condition associated with significant morbidity and reduced quality of life. In addition to challenges caused by their mood symptoms, parents affected with BPD harbor concerns about the mental health of their children. Among adult parents who perceive themselves to have BPD, this study aims to examine participants' coping methods; identify predictors of adaptation; assess parental perceptions of risks for mood disorders among their children; and describe the relationships among illness appraisals, coping, adaptation to one's own illness, and perceived risk to one's children. Parents who self-identified as having BPD completed a web-based survey that assessed dispositional optimism, coping, perceived illness severity, perceived etiology of BPD, perceived risk to offspring, and adaptation to BPD. Participants had at least one unaffected child who was 30 years of age or below. 266 parents were included in the analysis. 87% of parents endorsed a "somewhat greater" or "much greater" risk for mood disorders in one's child(ren) than someone without a family history. Endorsing a genetic/familial etiology to BPD was positively correlated with perceived risk for mood disorders in children (rs = .3, p < 0.01) and active coping with BDP (r = .2, p < 0.01). Increased active coping (beta = 0.4, p < 0.001) and dispositional optimism (beta = 0.3, p < 0.001) were positively associated with better adaptation, while using denial coping was negatively associated with adaptation (beta = -0.3, p < 0.001). The variables explained 55.2% of the variance in adaptation (F = 73.2, p < 0.001). Coping mediated the effect of perceived illness severity on adaptation. These data inform studies of interventions that extend beyond symptom management and aim to improve the psychological wellbeing of parents with BPD. Interventions targeted at illness perceptions and those aimed at enhancing coping should be studied for positive effects on adaptation. Parents with BPD may benefit from genetic counseling to promote active coping with their condition, and manage worry about perceived risk to their children.
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    • "The remission rate after acute treatment for mania is in the range of 40%–50%, and for depression is 25%–60%.7 In a recent large cohort study, only 60% of patients achieved remission during a 2-year follow-up period.8 Chronic persistence of symptoms can be expected in about 20% of cases, and social incapacity in about 30%.6 Judd et al9 carried out a follow-up study over 13 years and reported that bipolar patients were symptomatic during about half of the follow-up period. "
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    ABSTRACT: Lurasidone is a benzisothiazol derivative and an atypical antipsychotic approved by the US Food and Drug Administration for the acute treatment of adults with schizophrenia (October 2010) and bipolar 1 depression (June 2013). Lurasidone has a strong antagonistic property at the D2, serotonin (5-HT)2A, and 5-HT7 receptors, and partial agonistic property at the 5-HT1A receptor. Lurasidone also has lower binding affinity for the α2C and 5-HT2C receptor. Lurasidone is rapidly absorbed (time to maximum plasma concentration: 1-3 hours), metabolized mainly by CYP3A4 and eliminated by hepatic metabolism. In two large, well-designed, 6-week trials in adult patients with bipolar 1 depression, lurasidone monotherapy and adjunctive therapy with mood stabilizers were significantly more effective than placebo at improving depressive symptoms assessed using the Montgomery-Åsberg Depression Rating Scale total score. In both trials, lurasidone also reduced the Clinical Global Impression-Bipolar Severity depression score to a greater extent than placebo. In these two trials, discontinuation rates due to adverse events in the lurasidone group were small (<7%) and were not different from those of the placebo group. The most common adverse events in the lurasidone group were headache, nausea, somnolence, and akathisia. The changes in lipid profiles, weight, and parameters of glycemic control were minimal, and these findings were in line with those observed in schizophrenia trials. Further active comparator trials and long-term tolerability and safety data in bipolar patients are required. Lurasidone may be an option for the management of depressive symptoms in patients with bipolar 1 disorder, and it may be considered as a treatment alternative for patients who are at high risk for metabolic abnormalities.
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    ABSTRACT: Developing novel therapeutics and diagnostic tools based upon an understanding of neuroplasticity is critical in order to improve the treatment and ultimately the prevention of a broad range of nervous system disorders. In the case of mood disorders, such as major depressive disorder and bipolar disorder, where diagnoses are based solely on nosology rather than pathophysiology, there exists a clear unmet medical need to advance our understanding of the underlying molecular mechanisms and to develop fundamentally new mechanism experimental medicines with improved efficacy. In this context, recent preclinical molecular, cellular, and behavioral findings have begun to reveal the importance of epigenetic mechanisms that alter chromatin structure and dynamically regulate patterns of gene expression that may play a critical role in the pathophysiology of mood disorders. Here, we will review recent advances involving the use of animal models in combination with genetic and pharmacological probes to dissect the underlying molecular mechanisms and neurobiological consequence of targeting this chromatin-mediated neuroplasticity. We discuss evidence for the direct and indirect effects of mood stabilizers, antidepressants, and antipsychotics, among their many other effects, on chromatin-modifying enzmyes and on the epigenetic state of defined genomic loci, in defined cell types and in specific regions of the brain. These data, as well as findings from patient-derived tissue, have also begun to reveal alterations of epigenetic mechanisms in the pathophysiology and treatment of mood disorders. We summarize growing evidence supporting the notion that selectively targeting chromatin-modifying complexes, including those containing histone deacetylases (HDACs), provides a means to reversibly alter the acetylation state of neuronal chromatin and benefically impact neuronal activity-regulated gene transcription and mood-related behaviors. Looking beyond current knowledge, we discuss how high-resolution, whole-genome methodologies, such as RNA-sequencing (RNA-Seq) for transcriptome analysis and chromatin immunoprecipitation-sequencng (ChIP-Seq) for analyzing genome-wide occupancy of chromatin-associated factors, are beginning to provide an unprecedented view of both specific genomic loci as well as global properties of chromatin in the nervous system. These methodologies when applied to the characterization of model systems, including those of patient-derived induced pluripotent (iPS) cell and induced neurons (iNs), will greatly shape our understanding of epigenetic mechanisms and the impact of genetic variation on the regulatory regions of the human genome that can affect neuroplasticty. Finally, we point out critical unanswered questions and areas where additional data are needed in order to better understand the potential to target mechanisms of chromatin-mediated neuroplasticity for novel treatments of mood and other psychiatric disorders.
    Neuroscience 01/2013; 264. DOI:10.1016/j.neuroscience.2013.01.041 · 3.36 Impact Factor
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