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Bipolar Disorder: HELP
Articles from George Washington University
Based on 60 articles published since 2010
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These are the 60 published articles about Bipolar Disorder that originated from George Washington University during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. 2018

Yatham, Lakshmi N / Kennedy, Sidney H / Parikh, Sagar V / Schaffer, Ayal / Bond, David J / Frey, Benicio N / Sharma, Verinder / Goldstein, Benjamin I / Rej, Soham / Beaulieu, Serge / Alda, Martin / MacQueen, Glenda / Milev, Roumen V / Ravindran, Arun / O'Donovan, Claire / McIntosh, Diane / Lam, Raymond W / Vazquez, Gustavo / Kapczinski, Flavio / McIntyre, Roger S / Kozicky, Jan / Kanba, Shigenobu / Lafer, Beny / Suppes, Trisha / Calabrese, Joseph R / Vieta, Eduard / Malhi, Gin / Post, Robert M / Berk, Michael. ·Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. · Department of Psychiatry, University of Toronto, Toronto, ON, Canada. · Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. · Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada. · Departments of Psychiatry and Obstetrics & Gynaecology, Western University, London, ON, Canada. · Department of Psychiatry, McGill University, Montreal, QC, Canada. · Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. · Department of Psychiatry, University of Calgary, Calgary, AB, Canada. · Departments of Psychiatry and Psychology, Queen's University, Kingston, ON, Canada. · School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. · Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan. · Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil. · Bipolar and Depression Research Program, VA Palo Alto, Department of Psychiatry & Behavioral Sciences Stanford University, Stanford, CA, USA. · Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA. · Bipolar Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. · Department of Psychiatry, University of Sydney, Sydney, NSW, Australia. · Department of Psychiatry, George Washington University, Washington, DC, USA. · Deakin Univeristy, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Vic., Australia. ·Bipolar Disord · Pubmed #29536616.

ABSTRACT: The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

2 Editorial Relative absence of studies in bipolar depression. 2015

Post, Robert M. ·Department of Psychiatry, George Washington University School of Medicine, Bipolar Collaborative Network, Bethesda, Maryland, USA. ·Int Clin Psychopharmacol · Pubmed #26230177.

ABSTRACT: -- No abstract --

3 Review An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder. 2019

Faedda, Gianni L / Baldessarini, Ross J / Marangoni, Ciro / Bechdolf, Andreas / Berk, Michael / Birmaher, Boris / Conus, Philippe / DelBello, Melissa P / Duffy, Anne C / Hillegers, Manon H J / Pfennig, Andrea / Post, Robert M / Preisig, Martin / Ratheesh, Aswin / Salvatore, Paola / Tohen, Mauricio / Vázquez, Gustavo H / Vieta, Eduard / Yatham, Lakshmi N / Youngstrom, Eric A / Van Meter, Anna / Correll, Christoph U. ·Mood Disorders Center, New York, NY, USA. · International Consortium for Mood and Psychotic Disorders Research, McLean Hospital, Belmont, MA, USA. · Department of Psychiatry, Harvard Medical School, Mailman Research Center, McLean Hospital, Boston, MA, USA. · Department of Psychiatry-District 3, ULSS 9 Scaligera, Verona, Italy. · Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. · Department of Psychiatry, Psychotherapy and Psychosomatics, Vivantes Hospital am Urban and Vivantes Hospital im Friedrichschain, Charite Universitätsmedizin, Berlin, Germany. · IMPACT Strategic Research Centre, University Hospital Geelong, Barwon Health, Deakin University, Geelong, VIC, Australia. · Orygen, The National Center of Excellence in Youth Mental Health, Parkville, VIC, Australia. · The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Treatment and Early Intervention in Psychosis Program (TIPP), Département de Psychiatrie CHUV, Université de Lausanne, Lausanne, Switzerland. · Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Department of Psychiatry, Student Wellness Services, Queen's University, Kingston, ON, Canada. · Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany. · Bipolar Collaborative Network, Bethesda, MD, USA. · Department of Psychiatry, George Washington University School of Medicine, Washington, DC, USA. · Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland. · Psychiatry Section, Department of Neuroscience, School of Medicine, University of Parma, Parma, Italy. · Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. · Psychiatry, Queen's University, Kingston, ON, Canada. · Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Spain. · Department of Psychiatry, Mood Disorders Centre, University of British Columbia, Vancouver, BD, Canada. · Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA. · The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA. · The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, NY, USA. · Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. ·Bipolar Disord · Pubmed #31479581.

ABSTRACT: OBJECTIVES: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. METHODS: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies. RESULTS: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention. CONCLUSIONS: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.

4 Review Lithium and the Woozle effect. 2019

Kelly, Tammas. ·Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, District of Columbia. · The Depression and Bipolar Clinic of Colorado, Fort Collins, Colorado. ·Bipolar Disord · Pubmed #30738009.

ABSTRACT: OBJECTIVES: Lithium is the oldest and most-studied treatment for bipolar depression. Many treatment guidelines place lithium as a top treatment recommendation for bipolar depression; yet some guidelines do not recommend lithium at all. These discrepancies were explored by examining the following errors: the Woozle effect (evidence by citation), reference inflation (overreporting the findings of cited studies) and belief perseverance (maintaining a belief despite new contradictory evidence) as possible causes for these discrepancies. METHODS: Various search engines were used to find treatment guidelines for bipolar depression. The references cited in these guidelines were examined and analyzed in-depth. RESULTS: Ten guidelines recommend lithium as a first-line treatment for bipolar depression. Five did not recommend lithium at all for the treatment of bipolar depression. These discrepancies are remarkable. The references cited in the treatment guidelines were examined and do not favor lithium as a treatment for bipolar depression. The guidelines that favored lithium for the treatment of bipolar depression suffered numerous Woozle effects, reference inflation and belief perseverance are prevalent in guidelines that recommend lithium as a first-line treatment. All three errors are principally slippery slopes. These errors do not involve a deliberate attempt to mislead and may reflect failures of the peer review process. CONCLUSIONS: These errors may be common, as demonstrated in the case of lithium, interfering with our understanding and practice of evidence-based medicine. Both authors and journals need to guard against these types of errors in order to achieve sound evidence-based medical practices.

5 Review Prospective: Is bipolar disorder being overdiagnosed? 2018

Kelly, Tammas. ·Department of Psychiatry and Behavioral Sciences, George Washington University, Washington DC, USA. · The Depression & Bipolar Clinic of Colorado, Fort Collins, Colorado, USA. ·Int J Methods Psychiatr Res · Pubmed #29901255.

ABSTRACT: OBJECTIVES: Many studies indicate that bipolar disorders are underdiagnosed. Yet from 2007 to 2008, a series of publications asserted that bipolar disorders were being overdiagnosed. This review examines the methods used in the studies that reported bipolar disorders were being overdiagnosed. METHODS: A literature search for studies with original data related to overdiagnosis of bipolar disorders was performed. RESULTS: Four studies were found indicating bipolar disorders were being overdiagnosed. The Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders (SCID) was used in the diagnostic process. The studies compared the clinical diagnosis of bipolar disorder to a single SCID interview without interviewing family or reviewing old records. The studies assumed the SCID diagnosis was correct. CONCLUSIONS: Numerous concerns were found. The SCID frequently missed diagnosis of bipolar, the definitions of bipolar disorder are so narrow and conservative that the outcomes of the studies may have been predetermined. Ultimately, the studies compared the strength of a diagnosis made by a treating psychiatrist to a SCID diagnosis collected with virtually no information from the clinician. The assumption that the SCID diagnosis is always correct and the clinician is always wrong is unsupportable. The premise that bipolar disorders are being overdiagnosed is unsupported by reasonable science.

6 Review The New News about Lithium: An Underutilized Treatment in the United States. 2018

Post, Robert M. ·George Washington University School of Medicine, Bipolar Collaborative Network, Bethesda, MD, USA. ·Neuropsychopharmacology · Pubmed #28976944.

ABSTRACT: Lithium use for the treatment of mood disorders remains quite low, particularly in the United States compared with some European countries. Mogens Schou pioneered the study of lithium for prophylaxis of the recurrent mood disorder and encouraged its greater use. In an effort to further address the appropriate role of this drug, the multiple assets of lithium beyond its well-known antimanic effect are reviewed, and a brief summary of its side effects is outlined. It appears that lithium has positive effects in depression and suicide prevention, cognition, and reducing the incidence of dementia. It increases the length of telomeres and has positive effects in prevention of some medical illnesses. Lithium side-effect burden, especially its association with end-stage renal disease, may be less than many have surmised. New data indicate the importance of long-term prophylaxis after a first manic episode to lessen episode recurrence, allow cognition to recover to normal, and prevent various aspects of illness progression. After a first manic episode, 1 year of randomized treatment with lithium was superior to that of quetiapine, suggesting the importance of having lithium in the treatment regimen. Given the highly recurrent and progressive course of bipolar disorder sometimes even in the face of conventional treatment, the role and enhanced use of lithium deserves reconsideration.

7 Review More childhood onset bipolar disorder in the United States than Canada or Europe: Implications for treatment and prevention. 2017

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Leverich, Gabriele S / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, D.C., USA. Electronic address: robert.post@speakeasy.net. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Paracelsius Medical University, Salzburg, Austria. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·Neurosci Biobehav Rev · Pubmed #28119069.

ABSTRACT: Evidence of a high or increasing incidence of childhood onset bipolar disorder in the United States (US) has been viewed skeptically. Here we review evidence that childhood onsets of bipolar disorder are more common in the US than in Europe, treatment delays are longer, and illness course is more adverse and difficult. Epidemiological data and studies of offspring at high risk also support these findings. In our cohort of outpatients with bipolar disorder, two of the major vulnerability factors for early onset - genetics and environmental adversity in childhood - were also greater in the US than in Europe. An increased familial loading for multiple psychiatric disorders was apparent in 4 generations of the family members of the patients from the US, and that familial burden was linked to early onset bipolar disorder. Since both early onset and treatment delay are risk factors for a poor outcome in adulthood, new clinical, research, and public health initiatives are needed to begin to address and ameliorate this ongoing and potentially devastating clinical situation.

8 Review Illnesses in siblings of US patients with bipolar disorder relate to multigenerational family history and patients severity of illness. 2017

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington D.C., USA. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Department of Psychiatry and Psychotherapy, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Austria. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·J Affect Disord · Pubmed #27741468.

ABSTRACT: BACKGROUND: Patients with bipolar disorder from the US have more early-onset illness and a greater familial loading for psychiatric problems than those from the Netherlands or Germany (abbreviated here as Europe). We hypothesized that these regional differences in illness burden would extend to the patients siblings. METHODS: Outpatients with bipolar disorder gave consent for participation in a treatment outcome network and for filling out detailed questionnaires. This included a family history of unipolar depression, bipolar disorder, suicide attempt, alcohol abuse/dependence, drug abuse/dependence, and "other" illness elicited for the patients' grandparents, parents, spouses, offspring, and siblings. Problems in the siblings were examined as a function of parental and grandparental problems and the patients' adverse illness characteristics or poor prognosis factors (PPFs). RESULTS: Each problem in the siblings was significantly (p<0.001) more prevalent in those from the US than in those from Europe. In the US, problems in the parents and grandparents were almost uniformly associated with the same problems in the siblings, and sibling problems were related to the number of PPFs observed in the patients. LIMITATIONS: Family history was based on patient report. CONCLUSIONS: Increased familial loading for psychiatric problems extends through 4 generations of patients with bipolar disorder from the US compared to Europe, and appears to "breed true" into the siblings of the patients. In addition to early onset, a variety of PPFs are associated with the burden of psychiatric problems in the patients' siblings and offspring. Greater attention to the multigenerational prevalence of illness in patients from the US is indicated.

9 Review Risk Prediction Models in Psychiatry: Toward a New Frontier for the Prevention of Mental Illnesses. 2017

Bernardini, Francesco / Attademo, Luigi / Cleary, Sean D / Luther, Charles / Shim, Ruth S / Quartesan, Roberto / Compton, Michael T. ·School of Psychiatry, University of Perugia, Perugia, Italy. · Department of Epidemiology and Biostatistics, The George Washington University Milken Institute School of Public Health, Washington, DC, USA. · Department of Psychiatry, Southwest General Health Center, University Hospitals, Middleburg Heights, Ohio, USA. · Department of Psychiatry, Lenox Hill Hospital, New York, New York, USA. · Hofstra Northwell School of Medicine, Hempstead, New York, USA. · Department of Medicine, Division of Psychiatry, Clinical Psychology and Psychiatric Rehabilitation, University of Perugia, Santa Maria della Misericordia Hospital, Perugia, Italy. · Lenox Hill Hospital, Department of Psychiatry, 111 E. 77th St, New York, NY 10075. mcompton@northwell.edu. ·J Clin Psychiatry · Pubmed #27337225.

ABSTRACT: OBJECTIVE: We conducted a systematic, qualitative review of risk prediction models designed and tested for depression, bipolar disorder, generalized anxiety disorder, posttraumatic stress disorder, and psychotic disorders. Our aim was to understand the current state of research on risk prediction models for these 5 disorders and thus future directions as our field moves toward embracing prediction and prevention. DATA SOURCES: Systematic searches of the entire MEDLINE electronic database were conducted independently by 2 of the authors (from 1960 through 2013) in July 2014 using defined search criteria. Search terms included risk prediction, predictive model, or prediction model combined with depression, bipolar, manic depressive, generalized anxiety, posttraumatic, PTSD, schizophrenia, or psychosis. STUDY SELECTION: We identified 268 articles based on the search terms and 3 criteria: published in English, provided empirical data (as opposed to review articles), and presented results pertaining to developing or validating a risk prediction model in which the outcome was the diagnosis of 1 of the 5 aforementioned mental illnesses. We selected 43 original research reports as a final set of articles to be qualitatively reviewed. DATA EXTRACTION: The 2 independent reviewers abstracted 3 types of data (sample characteristics, variables included in the model, and reported model statistics) and reached consensus regarding any discrepant abstracted information. RESULTS: Twelve reports described models developed for prediction of major depressive disorder, 1 for bipolar disorder, 2 for generalized anxiety disorder, 4 for posttraumatic stress disorder, and 24 for psychotic disorders. Most studies reported on sensitivity, specificity, positive predictive value, negative predictive value, and area under the (receiver operating characteristic) curve. CONCLUSIONS: Recent studies demonstrate the feasibility of developing risk prediction models for psychiatric disorders (especially psychotic disorders). The field must now advance by (1) conducting more large-scale, longitudinal studies pertaining to depression, bipolar disorder, anxiety disorders, and other psychiatric illnesses; (2) replicating and carrying out external validations of proposed models; (3) further testing potential selective and indicated preventive interventions; and (4) evaluating effectiveness of such interventions in the context of risk stratification using risk prediction models.

10 Review Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention. 2016

Post, Robert M. ·George Washington University School of Medicine, Bipolar Collaborative Network, Bethesda, MD, USA. ·Bipolar Disord · Pubmed #27346321.

ABSTRACT: OBJECTIVES: The process of sensitization (increased responsivity) to the recurrence of stressors, affective episodes, and bouts of substance abuse that can drive illness progression in the recurrent affective disorders requires a memory of and increased reactivity to the prior exposures. A wealth of studies now supports the postulate that epigenetic mechanisms underlie both normal and pathological memory processes. METHODS: We selectively reviewed the literature pertinent to the role of epigenetics in behavioral sensitization phenomena and discuss its clinical implications. RESULTS: Epigenetics means above genetics and refers to environmental effects on the chemistry of DNA, histones (around which DNA is wound), and microRNA that change how easily genes are turned on and off. The evidence supports that sensitization to repeated stressor, affective episodes, and substance is likely based on epigenetic mechanisms and that these environmentally based processes can then become targets for prevention, early intervention, and ongoing treatment. Sensitization processes are remediable or preventable risk factors for a poor illness outcome and deserve increased clinical, public health, and research attention in the hopes of making the recurrent unipolar and bipolar affective disorders less impairing, disabling, and lethal by suicide and increased medical mortality. CONCLUSIONS: The findings that epigenetic chemical marks, which change in the most fundamental way how genes are regulated, mediate the long-term increased responsivity to recurrent stressors, mood episodes, and bouts of substance abuse should help change how the affective disorders are conceptualized and move treatment toward earlier, more comprehensive, and sustained pharmacoprophylaxis.

11 Review More illness in offspring of bipolar patients from the U.S. compared to Europe. 2016

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Leverich, Gabriele S / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington D.C., USA. Electronic address: Robert.post@speakeasy.net. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA; Julia S. Gouw Professor in Mood Disorders Research, Director, UCLA Mood Disorders Research Program, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·J Affect Disord · Pubmed #26655863.

ABSTRACT: BACKGROUND: Evidence suggests that patients with bipolar disorder from the United States have an earlier age of onset and a more difficult course of illness than those from Germany and the Netherlands. These characteristics were related to a greater family burden of psychiatric illness and the experience of more psychosocial adversity in childhood. We hypothesized that this greater illness burden would extend to the offspring of the US patients. METHODS: 968 outpatients (average age 41) with bipolar illness gave informed consent for participation in a treatment outcome network and filled out a detailed questionnaire about their illness and family history of illness, including whether their offspring had a diagnosis of depression, bipolar disorder, alcohol or substance abuse, suicide attempt or "other" illness. Of those with children, 356 were from the US and 132 were from Europe. RESULTS: Compared to the Europeans, offspring of patients from the US had significantly (p<0.001) more depression, bipolar disorder, drug abuse, and "other" illnesses. The number of illnesses in the offspring was related to the bipolar parent being from the US, having had childhood adversity, more than 20 prior episodes, and more parental psychiatric illness. CONCLUSIONS: While the findings are limited by their basis on self report, the distribution of the percentages in the US offspring are similar to those of Axelson et al. (2015) who used direct interviews. The higher burden of illness in the offspring and their in direct progenitors from the US compared to Europe warrant new attempts at better treatment and prevention.

12 Review Controversies in the psychopharmacology of bipolar disorder. 2014

Post, Robert M / Ostacher, Michael J / Singh, Vivek. ·From the Department of Psychiatry, George Washington University School of Medicine, Washington, DC, and the Bipolar Collaborative Network, Bethesda, Maryland. ·J Clin Psychiatry · Pubmed #25470106.

ABSTRACT: Few studies have examined the decision-making process for selecting a mood stabilizer or antipsychotic for patients with bipolar disorder. Despite a lack of evidence regarding their efficacy, conventional unimodal antidepressants continue to be used in bipolar treatment regimens. This article examines pharmacologic principles that can facilitate the evidence-based use of mood stabilizers and antipsychotics in patients with bipolar disorder. Choosing therapies for the maintenance of bipolar disorder, clinical decision making upon observation of a partial response, the use of combination therapies, and benefit/harm considerations when choosing a treatment for bipolar depression will be reviewed.

13 Review Maintenance treatment study designs in bipolar disorder: do they demonstrate that atypical neuroleptics (antipsychotics) are mood stabilizers? 2011

Goodwin, Frederick K / Whitham, Elizabeth A / Ghaemi, S Nassir. ·Center on Neuroscience, Medical Progress, and Society, The George Washington University School of Medicine, Washington, DC, USA. ·CNS Drugs · Pubmed #21936585.

ABSTRACT: In this conceptual review we argue that by certifying some of the atypical neuroleptics (or, if one prefers, antipsychotics) as indicated for the 'maintenance' treatment of bipolar disorder, the US FDA has created confusion in the field. These maintenance indications are based on studies using a 'relapse prevention' design, a design that does not address whether the agents tested can prevent new episodes of illness, i.e. recurrence prevention or true prophylaxis. We found that the relapse prevention design fails to prove that these agents are mood stabilizers because patients are pre-selected to respond to the study drug for an acute mood episode (mania) and when they relapse, they do so into an episode of the same polarity (i.e. mania). We believe that this represents withdrawal into the same mood episode that patients experienced before the maintenance study began, rather than prevention of a new mood episode, as research into the natural history of bipolar disorder indicates that such new episodes typically are of the opposite polarity. Thus, the inability of neuroleptics to prevent depression in such maintenance studies reflects the general inability to prevent any new mood episode recurrence (which we believe should be defined as 6 months or longer after the index episode). If one defines a mood stabilizer, as we do, as a drug that prevents new episodes of mania and depression in monotherapy, then these studies do not show that atypical neuroleptics are mood stabilizers. Future maintenance research studies in bipolar disorder should use the prophylaxis design (i.e. without pre-selection of drug responders), rather than the relapse prevention design.

14 Review Tolerance to the prophylactic effects of carbamazepine and related mood stabilizers in the treatment of bipolar disorders. 2011

Post, Robert M / Weiss, Susan R B. ·Department of Psychiatry, George Washington University, Washington, DC, USA. robert.post@speakeasy.net ·CNS Neurosci Ther · Pubmed #21159150.

ABSTRACT: Tolerance development after successful long-term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamazepine or lamotrigine on amgydala-kindled seizures. In this model tolerance does not have a pharmacokinetic basis, but is contingent upon the drug being present in the brain at the time of amygdala stimulation. The occurrence of seizures in the absence of drug is sufficient to reverse tolerance and re-establish anticonvulsant efficacy. Based on the model, we hypothesize that some episode-induced compensatory adaptive changes in gene expression fail to occur in tolerant subjects and that episodes off medication re-induce these changes and renew drug effectiveness. Approaches that slow or reverse tolerance development in the animal model are reviewed so that they can be tested for their applicability in the clinic. Criteria for assessing tolerance development are offered in the hope that this will facilitate a more systemic literature about its prevalence, prevention, and reversal. Careful longitudinal monitoring of episode occurrence is essential to understanding tolerance development in the affective disorder and its treatment.

15 Clinical Trial Adjunctive Maintenance Lamotrigine for Pediatric Bipolar I Disorder: A Placebo-Controlled, Randomized Withdrawal Study. 2015

Findling, Robert L / Chang, Kiki / Robb, Adelaide / Foster, Vicki J / Horrigan, Joseph / Krishen, Alok / Wamil, Art / Kraus, John E / DelBello, Melissa. ·Johns Hopkins University and Kennedy Krieger Institute, Baltimore, MD. Electronic address: RFindli1@jhmi.edu. · Lucille Packard Children's Hospital at Stanford, Stanford, CA. · Children's National Health System and George Washington University, Washington, DC. · GlaxoSmithKline at the time of the study; PAREXEL International, Research Triangle Park, NC. · GlaxoSmithKline at the time of the study; Neuren Pharmaceuticals, Melbourne, Australia. · GlaxoSmithKline at the time of the study. · GlaxoSmithKline, Research Triangle Park, NC. · University of Cincinnati College of Medicine, Cincinnati, OH. ·J Am Acad Child Adolesc Psychiatry · Pubmed #26598477.

ABSTRACT: OBJECTIVE: This study aimed to compare the efficacy of lamotrigine versus placebo in 10- to 17-year-olds with bipolar I disorder (BP-I) who were receiving conventional bipolar disorder treatment. METHOD: In this randomized withdrawal trial, patients with BP-I of at least moderate severity received lamotrigine during an ≤18-week open-label phase. Patients who maintained a stable lamotrigine dose for ≥2 weeks and Clinical Global Impression-Bipolar Severity of Illness (CGI-BP[S]) score of ≤3 for ≥6 consecutive weeks were randomized to double-blind lamotrigine or placebo for ≤36 weeks. RESULTS: Of 301 patients enrolled, 298 comprised the open-label intention-to-treat population, with 173 (58%) randomized. Of these patients, 41 (24%) completed the study. In the open-label phase, the mean (SD) baseline CGI-BP(S) rating was 4.4 (0.57), and the mean (standard error [SE]) time to stabilization was 101 (1.6) days. During the randomized phase, mean (SE) time to occurrence of a bipolar event (TOBE) for lamotrigine versus placebo (primary endpoint) was 155 (14.7) versus 50 (3.8), 163 (12.2) versus 120 (12.2), and 136 (15.4) versus 107 (13.8) days for the 3 index mood states (depressed, manic/hypomanic, mixed). The primary stratified log-rank analysis of TOBE was not statistically significant (hazard ratio [HR] = 0.63; p = .072); however, the prespecified Cox regression analysis favored lamotrigine (p = .047). In 13- to 17-year-olds, log-rank analysis of TOBE significantly favored lamotrigine (HR = 0.46; p = .015), but not in 10- to 12-year-olds (HR = 0.93; p = .877). Dermatologic events were reported in 4% (open-label phase) and 2% (randomized phase) of patients receiving lamotrigine. Suicidality-related adverse events were reported in 7% (open-label phase) and 7% (randomized phase) of patients receiving lamotrigine. CONCLUSION: Although the primary analysis failed to detect a benefit of add-on lamotrigine for BP-I in 10- to 17-year-olds, lamotrigine may be effective in a subset of older adolescents. Clinical trial registration information-Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients; http://clinicaltrials.gov/; NCT00723450.

16 Clinical Trial Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment. 2015

Walkup, John T / Wagner, Karen Dineen / Miller, Leslie / Yenokyan, Gayane / Luby, Joan L / Joshi, Paramjit T / Axelson, David A / Robb, Adelaide / Salpekar, Jay A / Wolf, Dwight / Sanyal, Abanti / Birmaher, Boris / Vitiello, Benedetto / Riddle, Mark A. ·Weill Cornell Medical College, New York Presbyterian Hospital, New York. Electronic address: jtw9001@med.cornell.edu. · University of Texas Medical Branch, Galveston. · Johns Hopkins University School of Medicine, Baltimore. · Johns Hopkins Bloomberg School of Public Health. · Washington University in St. Louis. · Children's National Medical Center, George Washington University School of Medicine, Washington, DC. · Nationwide Children's Hospital and The Ohio State University/Wexner Medical Center, Columbus. · University of Pittsburgh Medical Center/Western Psychiatric Institute and Clinic, Pittsburgh. · National Institute of Mental Health (NIMH), Bethesda, MD. ·J Am Acad Child Adolesc Psychiatry · Pubmed #26598476.

ABSTRACT: OBJECTIVE: The Treatment of Early Age Mania (TEAM) study evaluated lithium, risperidone, and divalproex sodium (divalproex) in children with bipolar I disorder who were naive to antimanic medication, or were partial or nonresponders to 1 of 3 study medications. This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders, respectively. METHOD: TEAM is a randomized, controlled trial of individuals (N = 379) aged 6 to 15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (mixed or manic phase). Participants (n = 154) in this report were either nonresponders or partial responders to 1 of the 3 study medications. Nonresponders (n = 89) were randomly assigned to 1 of the other 2 antimanic medications and cross-tapered. Partial responders (n = 65) were randomly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication. Adverse event (AE) rates are reported only for the add-on group. RESULTS: Response rate for children switched to risperidone (47.6%) was higher than for those switched to either lithium (12.8%; p = .005; number needed to treat [NNT] = 3; 95% CI = 1.71-9.09) or divalproex (17.2%; p = .03; NNT = 3; 95% CI = 1.79-20.10); response rate for partial responders who added risperidone (53.3%) was higher than for those who added divalproex (0%; p = .0002; NNT = 2; 95% CI = 1.27-3.56) and trended higher for lithium (26.7%; p = .07; NNT = 4). Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication. Weight gain (kg) was observed for all add-on medications: lithium add-on (n = 29 of 30) = 1.66 ± 1.97; risperidone add-on (n = 15 of 15) = 2.8 ± 1.34; divalproex add-on (n = 19 of 20) = 1.42 ± 1.96. There was no evidence at the 5% significance level that the average weight gain was different by study medication for partial responders (p = .07, 1-way analysis of variance). CONCLUSION: Risperidone appears to be more useful than lithium or divalproex for children with bipolar I disorder and other comorbid conditions who are nonresponders or partial responders to an initial antimanic medication trial. Clinical trial registration information-Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM); http://clinicaltrials.gov/; NCT00057681.

17 Clinical Trial Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study. 2015

Salpekar, Jay A / Joshi, Paramjit T / Axelson, David A / Reinblatt, Shauna P / Yenokyan, Gayane / Sanyal, Abanti / Walkup, John T / Vitiello, Benedetto / Luby, Joan L / Wagner, Karen Dineen / Nusrat, Nasima / Riddle, Mark A. ·Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore. Electronic address: Salpekar@kennedykrieger.org. · Children's National Medical Center and George Washington University, Washington, DC; American Academy of Child and Adolescent Psychiatry (AACAP) and with the American Board of Psychiatry and Neurology (ABPN). · Nationwide Children's Hospital and The Ohio State University, Columbus. · Johns Hopkins University School of Medicine. · Johns Hopkins Biostatistics Center at Johns Hopkins Bloomberg School of Public Health. · New York Presbyterian Hospital-Weill Cornell Medical College, New York. · National Institute of Mental Health (NIMH), Bethesda, MD. · Washington University in St. Louis. · University of Texas Medical Branch at Galveston. · Children's National Medical Center and George Washington University, Washington, DC. ·J Am Acad Child Adolesc Psychiatry · Pubmed #26598475.

ABSTRACT: OBJECTIVE: To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder. METHOD: The Treatment of Early Age Mania (TEAM) study is a multicenter, prospective, randomized, masked comparison of divalproex sodium (VAL), lithium carbonate (LI), and risperidone (RISP) in an 8-week parallel clinical trial. A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder, mixed or manic, aged 6 to 15 years were enrolled. The primary outcome measure was improvement on the Clinical Global Impression scale for depression (CGI-BP-I-D). Secondary outcome measures included the Children's Depression Rating Scale (CDRS-R) and suicidality status. Statistics included longitudinal analysis of outcomes using generalized linear mixed models with random intercept both for the complete data set and by using last observation carried forward. RESULTS: CGI-BP-I-D ratings were better in the RISP group (60.7%) as compared to the LI (42.2%; p = .03) or VAL (35.0%; p = .003) groups from baseline to the end of the study. CDRS scores in all treatment groups improved equally by study end. In week 1, scores were lower with RISP compared to VAL (mean = 4.72, 95% CI = 2.67, 6.78), and compared to LI (mean = 3.63, 95% CI = 1.51, 5.74), although group differences were not present by the end of the study. Suicidality was infrequent, and there was no overall effect of treatment on suicidality ratings. CONCLUSION: Depressive symptoms, present in the acutely manic or mixed phase of pediatric bipolar disorder, improved with all 3 medications, though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome. Clinical trial registration information-Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM); http://clinicaltrials.gov; NCT00057681.

18 Article Debate: Fomenting controversy regarding pediatric bipolar disorder. 2019

Goldstein, Benjamin I / Post, Robert M / Birmaher, Boris. ·Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre. · Department of Psychiatry, University of Toronto Faculty of Medicine. · Bipolar Collaborative Network. · George Washington University School of Medicine. · Child and Adolescent Bipolar Spectrum Services, University of Pittsburgh Medical Center. · Department of Psychiatry, University of Pittsburgh School of Medicine. ·Child Adolesc Ment Health · Pubmed #31866767.

ABSTRACT: Does bipolar disorder exist in children? How common is childhood-onset bipolar disorder among adults? Are bipolar spectrum conditions relevant? Answers to these questions are key drivers of the design and interpretation of epidemiologic studies of pediatric bipolar disorder. In our commentary, we assert that Parry and colleagues have selectively attended to certain findings that support their thesis, while ignoring contradictory findings, and that they have assigned excessive meaning to relatively pedestrian methodologic limitations. Their singling out of the United States is done with criticism but without critical appraisal. We highlight the flawed logic and inferential leaps that sustain Parry et al's criticism despite contradictory information dating back over a century.

19 Article Beyond evidence-based treatment of bipolar disorder: Rational pragmatic approaches to management. 2019

Post, Robert M / Yatham, Lakshmi N / Vieta, Eduard / Berk, Michael / Nierenberg, Andrew A. ·Clinical Professor of Psychiatry, George Washington University School of Medicine, Bipolar Collaborative Network, Bethesda, MD, USA. · University of British Columbia, Vancouver, BC, Canada. · Department of Psychiatry, Vancouver Coastal Health/Providence Healthcare, Vancouver, BC, Canada. · Department of Psychiatry and Psychology, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. · Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Vic, Vic., Australia. · Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, the Florey Institute for Neuroscience and Mental Health, Melbourne, Vic., Australia. · Department of Psychiatry, University of Melbourne, Melbourne, Vic., Australia. · Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·Bipolar Disord · Pubmed #31343802.

ABSTRACT: The evidence for efficacy of many currently available treatments for bipolar disorder is based on studies of nonrefractory patients with bipolar disorder. Therefore, not surprisingly, most treatment recommendations and guidelines for the treatment of bipolar disorder and its many comorbidities depend heavily on data from placebo controlled randomized clinical trials (RCTs), but these RCTs provide little direction for the clinician as to what next steps might be optimal in non- or partial-responders and in those with ongoing medical and psychiatric comorbidities. Given this and the paucity of RCTs at later treatment junctures, we thought it appropriate to begin a discussion of the quality of the data that some experts in the field might consider using in choosing and sequencing drugs and their combination. We acknowledge that many other clinical investigators may prefer very different sequences, but thought the suggestions offered here might be useful to some clinicians in the field, might start discussions of other options in the literature, and, at the same time, provide a preliminary outline for a new round of much-needed clinical trials to better inform clinical practice. Given the very wide range of the quality of the data and clinical principles on which the current suggestions are based, only minimal references are included and a comprehensive review of the literature supporting each option would be outside the scope of this manuscript.

20 Article Bipolar II Disorder: Not So Sure It Is Time for Something New. 2019

Post, Robert M. ·1 Bipolar Collaborative Network, George Washington University School of Medicine, Bethesda, MD, USA. ·Can J Psychiatry · Pubmed #31104479.

ABSTRACT: -- No abstract --

21 Article Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scale. 2019

Kinrys, Gustavo / Bowden, Charles L / Nierenberg, Andrew A / Hearing, Casey M / Gold, Alexandra K / Rabideau, Dustin J / Sylvia, Louisa G / Gao, Keming / Kamali, Masoud / Bobo, William V / Tohen, Mauricio / Deckersbach, Thilo / McElroy, Susan L / Ketter, Terence A / Shelton, Richard C / Friedman, Edward S / Calabrese, Joseph R / McInnis, Melvin G / Kocsis, James / Thase, Michael E / Singh, Vivek / Reilly-Harrington, Noreen A. ·Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: gkinrys@mgh.harvard.edu. · Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. · Department of Psychology, The George Washington University, Washington, DC, USA. · Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA. · Department of Biostatistics, Harvard University, Cambridge, MA, USA. · Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA. · Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. · Department of Psychiatry, University of New Mexico, Health Sciences Center, Albuquerque, NM, USA. · Lindner Center of HOPE, Mason, OH, USA; Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, NY, USA. · Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. ·J Affect Disord · Pubmed #30580198.

ABSTRACT: BACKGROUND: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial. METHODS: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS. RESULTS: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics. LIMITATIONS: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders. CONCLUSIONS: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.

22 Article Testing a clinical staging model for bipolar disorder using longitudinal life chart data. 2019

van der Markt, Afra / Klumpers, Ursula Mh / Draisma, Stasja / Dols, Annemiek / Nolen, Willem A / Post, Robert M / Altshuler, Lori L / Frye, Mark A / Grunze, Heinz / Keck, Paul E / McElroy, Susan L / Suppes, Trisha / Beekman, Aartjan Tf / Kupka, Ralph W. ·Department of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, University Medical Center, University of Groningen, Groningen, The Netherlands. · Bipolar Collaborative Network, Bethesda, Maryland. · Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, District of Columbia. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California. · Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, California. · Department of Psychiatry, Mayo Clinic, Rochester, Minnesota. · Klinikum am Weissenhof, Weinsberg Germany & Paracelsus Medical University, Nuremberg, Germany. · University of Cincinnati College of Medicine, Cincinnati, Ohio. · Lindner Center of HOPE, Mason, Ohio. · Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, Ohio. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California. · V.A. Palo Alto Health Care System, Palo Alto, California. ·Bipolar Disord · Pubmed #30447123.

ABSTRACT: OBJECTIVE: Bipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages. METHODS: Using retrospectively reported longitudinal life chart data of 99 subjects from the Stanley Foundation Bipolar Network Naturalistic Follow-up Study, the occurrence, duration and timely sequence of stages 2-4 were determined per month. A multi-state model was used to calculate progression rates and identify determinants of illness progression. Stages 0, 1 and several other variables were added to the multi-state model to determine their influence on the progression rates. RESULTS: Five years after onset of BD (stage 2), 72% reached stage 3 (recurrent episodes) and 21% had reached stage 4 (continuous episodes), of whom 8% recovered back to stage 3. The progression from stage 2 to 3 was increased by a biphasic onset for both the depression-mania and the mania-depression course and by male sex. CONCLUSIONS: Staging is a useful model to determine illness progression in longitudinal life chart data. Variables influencing transition rates were successfully identified.

23 Article Revising Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for the bipolar disorders: Phase I of the AREDOC project. 2018

Parker, Gordon / Tavella, Gabriela / Macqueen, Glenda / Berk, Michael / Grunze, Heinz / Deckersbach, Thilo / Dunner, David L / Sajatovic, Martha / Amsterdam, Jay D / Ketter, Terence A / Yatham, Lakshmi N / Kessing, Lars Vedel / Bassett, Darryl / Zimmerman, Mark / Fountoulakis, Kostas N / Duffy, Anne / Alda, Martin / Calkin, Cynthia / Sharma, Verinder / Anand, Amit / Singh, Manpreet K / Hajek, Tomas / Boyce, Philip / Frey, Benicio N / Castle, David J / Young, Allan H / Vieta, Eduard / Rybakowski, Janusz K / Swartz, Holly A / Schaffer, Ayal / Murray, Greg / Bayes, Adam / Lam, Raymond W / Bora, Emre / Post, Robert M / Ostacher, Michael J / Lafer, Beny / Cleare, Anthony J / Burdick, Katherine E / O'Donovan, Claire / Ortiz, Abigail / Henry, Chantal / Kanba, Shigenobu / Rosenblat, Joshua D / Parikh, Sagar V / Bond, David J / Grunebaum, Michael F / Frangou, Sophia / Goldberg, Joseph F / Orum, Margo / Osser, David N / Frye, Mark A / McIntyre, Roger S / Fagiolini, Andrea / Manicavasagar, Vijaya / Carlson, Gabrielle A / Malhi, Gin S. ·1 School of Psychiatry - University of New South Wales and Black Dog Institute, Randwick, NSW, Australia. · 2 Department of Psychiatry, University of Calgary, Calgary, AB, Canada. · 3 IMPACT SRC, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia. · 4 Department of Psychiatry, Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health and the Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia. · 5 Allgemeinpsychiatrie Ost, Klinikum am Weissenhof, Weinsberg, Germany. · 6 Paracelsus Medical Private University (PMU) Nuremberg, Nuremberg, Germany. · 7 Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · 8 Center for Anxiety & Depression, Mercer Island, WA, USA. · 9 Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA. · 10 School of Medicine, Case Western Reserve University, Cleveland, OH, USA. · 11 Depression Research Unit, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · 12 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · 13 Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada. · 14 The Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. · 15 Division of Psychiatry, School of Medicine, The University of Western Australia, Perth, WA, Australia. · 16 Department of Psychiatry and Human Behavior, Brown University, and Rhode Island Hospital, Providence, RI, USA. · 17 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. · 18 Department of Psychiatry, Queen's University, Kingston, ON, Canada. · 19 Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. · 20 Departments of Psychiatry and Medical Neuroscience, Dalhousie University, Halifax, NS, Canada. · 21 Department of Psychiatry, Western University, London, ON, Canada. · 22 Center for Behavioral Health, Cleveland Clinic, Cleveland, OH, USA. · 23 Discipline of Psychiatry, Westmead Clinical School, Sydney Medical School, University of Sydney, Westmead, NSW, Australia. · 24 Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, ON, Canada. · 25 The University of Melbourne and St Vincent's Hospital, Melbourne, VIC, Australia. · 26 The Centre for Affective Disorders, King's College London, London, UK. · 27 Hospital Clinic of Barcelona, Clinic Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. · 28 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. · 29 Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. · 30 Department of Psychiatry, University of Toronto, Toronto, ON, Canada. · 31 Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia. · 32 Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Carlton, VIC, Australia. · 33 Department of Psychiatry, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey. · 34 School of Medicine & Health Sciences, The George Washington University, Washington, DC, USA. · 35 Bipolar Collaborative Network, Bethesda, MD, USA. · 36 Department of Psychiatry, VA Palo Alto Health Care System, Palo Alto, CA, USA. · 37 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · 38 Department of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil. · 39 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK. · 40 Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · 41 AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d'Addictologie, Université Paris-Est Créteil Val de Marne, Créteil, France. · 42 Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan. · 43 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · 44 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA. · 45 New York State Psychiatric Institute, Columbia University, New York, NY, USA. · 46 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · 47 Open Sky Psychology, Ryde, NSW, Australia. · 48 Veterans Affairs Boston Healthcare System, Harvard Medical School, Boston, MA, USA. · 49 Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. · 50 Department of Psychiatry, University of Toronto and Brain and Cognition Discovery Foundation, Toronto, ON, Canada. · 51 Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. · 52 Psychology Clinic, University of New South Wales, Sydney, NSW, Australia. · 53 Psychology Clinic, Black Dog Institute, Randwick, NSW, Australia. · 54 Department of Psychiatry and Behavioral Health, Stony Brook University School of Medicine, Stony Brook, NY, USA. · 55 CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia. · 56 Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW, Australia. · 57 Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. ·Aust N Z J Psychiatry · Pubmed #30378461.

ABSTRACT: OBJECTIVE:: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. METHOD:: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. RESULTS:: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge 'impairment' (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. CONCLUSION:: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.

24 Article Childhood Physical and Sexual Abuse Predicts Suicide Risk in a Large Cohort of Veterans. 2018

Koola, Maju Mathew / Ahmed, Anthony O / Sebastian, Joseph / Duncan, Erica J. ·Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine and Health Sciences, 2300 I St NW, Washington, DC 20037. majumkoola@gmail.com. · Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. · Department of Psychiatry, Weill Cornell School of Medicine, New York, New York, USA. · Department of Family Medicine, Aultman Hospital, Canton, Ohio, USA. · Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA. ·Prim Care Companion CNS Disord · Pubmed #30152644.

ABSTRACT: Objective: To examine whether childhood physical and sexual abuse is a significant predictor of suicide risk in veterans. Methods: This study was a retrospective chart review of 4,709 patients admitted to a psychiatric ward (August 2004 through July 2014) at the Atlanta Veterans Affairs Medical Center (VAMC). Sociodemographic and clinical data and history of childhood (aged ≤ 18 years) physical and sexual abuse were obtained from the patients' electronic health records. Suicide risk data of patients who attempted and completed suicide were obtained from the Atlanta VAMC suicide high-risk team. Binary logistic regressions with maximum likelihood estimation method were used to examine the association of demographic (age, sex, marital status, race, service) and clinical (psychiatric diagnoses, number of hospital admissions, and length of stay) variables and childhood physical and sexual abuse and type with suicide behavior. Results: The combination of childhood physical and sexual abuse, number of admissions to a psychiatric inpatient unit, and major depressive disorder (MDD) were the best predictors of enhanced suicide risk (P < .001). This combination accounted for 9.9% variance in suicide risk and correctly classified 83% of cases into respective suicide versus nonsuicide risk groups. Additional significant predictors were bipolar disorder (P < .001) and cocaine use disorder (P = .02). Surprisingly, diagnosis of schizophrenia predicted a reduced risk. Conclusions: To our knowledge, this study is the first to shed light on the interaction of childhood physical and sexual abuse and suicide risk in a large cohort of veterans. In the final model, childhood physical and sexual abuse, number of psychiatric admissions, and MDD were the best predictors of increased suicide risk. Schizophrenia was a protective factor in this veteran cohort.

25 Article Botulinum toxin therapy of bipolar depression: A case series. 2018

Finzi, E / Kels, L / Axelowitz, J / Shaver, B / Eberlein, C / Krueger, T H / Wollmer, M A. ·Department of Psychiatry & Behavioral Sciences, George Washington School of Medicine, Washington,DC, 20037, USA. Electronic address: finzieric@gmail.com. · Department of Psychiatry & Behavioral Sciences, George Washington School of Medicine, Washington,DC, 20037, USA; University of the Incarnate Word School of Osteopathic Medicine, San Antonio, TX, 78209, USA. · Department of Psychiatry & Behavioral Sciences, George Washington School of Medicine, Washington,DC, 20037, USA. · Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany. · Asklepios Clinic North-Ochsenzoll, Asklepios Campus Hamburg, Medical Faculty, Semmelweis University, Germany. ·J Psychiatr Res · Pubmed #29982082.

ABSTRACT: We and others have recently found that botulinum toxin injected into the brow muscles has significant antidepressant properties as compared to placebo in randomized controlled trials in patients with major depressive disorder. However, data for the treatment of bipolar depression with botulinum toxin is lacking. We report here six patients with bipolar disorder experiencing moderate to severe depressive episodes who were treated on a compassionate basis with botulinum toxin given their persistent depressive symptoms and adverse side effects from medications. Four of six patients with bipolar depression experienced a remission following treatment with botulinum toxin, and the other two patients experienced a reduction of depressive symptoms. When the effect of botulinum toxin on the frown muscles began to wear off, depressive symptoms returned and retreatment with botulinum toxin provided successful relief of depressive symptoms again.

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