Bipolar Disorder: Bauer M

Pfennig A, Weikert B, Falkai P, Gotz T, Kopp I, Sasse J, Scherk H, Strech D, Bauer M. · Klinik und Poliklinik fur Psychiatrie und Psychotherapie, Universitatsklinik-kum Carl Gustav Carus, Technische Universitat Dresden. · Nervenarzt. · Pubmed #18389205 No free full text.

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Ghaemi SN, Bauer M, Cassidy F, Malhi GS, Mitchell P, Phelps J, Vieta E, Youngstrom E, Anonymous00020. · Bipolar Disorder Research Program, Department of Psychiatry, Emory University, Atlanta, GA 30322, USA. · Bipolar Disord. · Pubmed #18199230 No free full text.

Abstract: The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.

Bauer M. · No affiliation provided · Psychiatr Prax. · Pubmed #10705594 No free full text.

Abstract: The "difficult patient" does not exist in psychiatric textbooks but rather in every day practice. A solely diagnostic description is not very useful, the categorisation into three separate subgroups by Sheets et al. (1982) on the contrary helps a lot. Three case studies describes typical treatment-situations with "difficult patients" in a community psychiatric setting.

Sasse J, Pilhatsch M, Forsthoff A, Grunze H, Neutze J, Pfennig A, Schmitz B, Schwenkhagen A, Bauer M. · Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstrasse 74, 01307, Dresden, Deutschland. · Nervenarzt. · Pubmed #19229511 No free full text.

Abstract: This manuscript summarizes specific issues in the disease course and pharmacological treatment of women with bipolar disorders. Gender differences relevant to the female biology manifest in symptoms, outcome, and course. The preponderance of depressive symptoms is typical, and the risk of rapid cycling is estimated to be eight times higher for women than for men. Comorbid anxiety and eating disorders occur more frequently in female patients. In planning treatment it is important to take fertility, contraception, and pregnancy into consideration and adjust the pharmacotherapy to harmonize with the patient's current phase of life. Little is known about potential sexual dysfunctions of bipolar women. Further research should include clinical and observational studies focusing on gender-specific differences in symptomatology, treatment, and long-term outcome of bipolar disorders.

Bauer M, Juckel G, Correll CU, Leopold K, Pfennig A. · Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, Dresden, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #18985295 No free full text.

Abstract: The combination of a long undetected illness and significant psychosocial impairment renders early identification and intervention a vital role in bipolar disorders. Early detection forms the basis for adequate education and for treatment from the beginning. Several lines of evidence indicate that the characterization of early phases in the development of bipolar disorders is feasible. Risk factors for the development of bipolar disorders have been established and a manic prodrome has been characterized that is sufficiently long to allow recognition and, potentially, intervention. Centers specifically focussing on early detection and prevention of bipolar disorders need to be established. More research in this field is warranted including both groups of symptomatic subjects and symptom-free persons, with and without a positive family history.

Gallinat J, Bauer M, Heinz A. · Klinik für Psychiatrie und Psychotherapie, Charité Universitatsmedizin Berlin, Campus Mitte, Berlin, Germany. · Neurodegener Dis. · Pubmed #18520162 No free full text.

Abstract: Major psychiatric disorders, including schizophrenia, bipolar disorder and substance addiction, are partly heritable and show a multifactorial pattern of heredity. Although the introduction of explicit diagnostic criteria has improved clinical research on psychiatric disorders, the concept is only of limited use for exploring their genetic underpinnings. On the behavioral level, psychopathological symptoms can hardly separate the many pathophysiological subgroups. Contrary to nosological categories, biologically based phenotypes - referred to as intermediate phenotypes - consisting of neuropsychological, electrophysiological, functional and structural brain imaging parameters, could represent the genetic basis more directly. Thus intermediate phenotypes are being targeted in current molecular genetic investigations. In this article, we review existing data on the effects of genetic variation in the dopamine and serotonin systems (catechol-O-methyltransferase, the serotonin-transporter-linked polymorphic region) on the morphometric, metabolic and functional characteristics of the cerebral cortex and limbic structures. The gene-driven modulation of these brain circuits is discussed with regard to their behavioral correlates and their role for psychiatric diseases. Furthermore, recently identified putative susceptibility genes for schizophrenia (neuregulin 1, dysbindin, G72) are briefly discussed.

Schmitt A, Parlapani E, Bauer M, Heinsen H, Falkai P. · Department of Psychiatry, University of Goettingen, Germany. · Clinics (Sao Paulo). · Pubmed #18438581 links to  free full text

Abstract: It is widely accepted that neurobiological abnormalities underlie the symptoms of psychiatric disorders such as schizophrenia and unipolar or bipolar affective disorders. New molecular methods, computer-assisted quantification techniques and neurobiological investigation methods that can be applied to the human brain are all used in post-mortem investigations of psychiatric disorders. The following article describes modern quantitative methods and recent post-mortem findings in schizophrenia and affective disorders. Using our brain bank as an example, necessary considerations of modern brain banking are addressed such as ethical considerations, clinical work-up, preparation techniques and the organization of a brain bank, the value of modern brain banking for investigations of psychiatric disorders is summarized.

Bauer M, Beaulieu S, Dunner DL, Lafer B, Kupka R. · Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · Bipolar Disord. · Pubmed #18199234 No free full text.

Abstract: OBJECTIVES: This paper reviews the literature to examine the DSM-IV diagnostic criteria for rapid cycling in bipolar disorder. METHODS: Studies on the clinical characteristics of rapid cycling bipolar disorder were reviewed. To identify relevant papers, literature searches using PubMed and MEDLINE were undertaken. RESULTS: First observed in the prepharmacologic era, rapid cycling subsequently has been associated with a relatively poor response to pharmacologic treatment. Rapid cycling can be conceptualized as either a high frequency of episodes of any polarity or as a temporal sequence of episodes of opposite polarity. The DSM-IV defines rapid cycling as a course specifier, signifying at least four episodes of major depression, mania, mixed mania, or hypomania in the past year, occurring in any combination or order. It is estimated that rapid cycling is present in about 12-24% of patients at specialized mood disorder clinics. However, apart from episode frequency, studies over the past 30 years have been unable to determine clinical characteristics that define patients with rapid cycling as a specific subgroup. Furthermore, rapid cycling is a transient phenomenon in many patients. CONCLUSIONS: While a dimensional approach to episode frequency as a continuum between the extremes of no cycling and continuous cycling may be more appropriate and provide a framework to include ultra-rapid and ultradian cycling, the evidence does not exist today to refine the DSM-IV definition in a less arbitrary manner. Continued use of the DSM-IV definition also enables comparisons between past and future studies, and it should be included in the next release of the ICD. Further scientific investigation into rapid cycling is needed. In addition to improving the diagnostic criteria, insight into neurophysiologic mechanisms of mood switching and episode frequency may have important implications for clinical care.

Grunze H, Adli M, Bauer M, Berger M, Bergmann A, Bräunig P, Bschor T, Falkai P, Gastpar M, Greil W, Kasper S, Krüger S, Laux G, Müller WE, Naber D, Walden J. · Psychiatrische Klinik LMU, München. · Fortschr Neurol Psychiatr. · Pubmed #17427043 No free full text.

Abstract: During recent years valproate has been established as a cornerstone for the drug-treatment of bipolar disorder. In Germany, valproate was licensed both for the treatment of acute mania and for maintenance treatment in summer 2005. At this occasion, this review summarises the scientific evidence and clinical experience of well-known experts with valproate-treatment. It was concluded that valproate will continue to be of high clinical significance despite the recent increase of treatment alternatives, both in monotherapy and combination treatment of acute mania, mixed states and maintenance treatment.

Hauser M, Pfennig A, Ozgürdal S, Heinz A, Bauer M, Juckel G. · Early Recognition Center of Beginning Psychoses, Department of Psychiatry, Charité, Campus Mitte, Berlin, Germany. · Eur Psychiatry. · Pubmed #17142013 No free full text.

Abstract: Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale.

Bauer M, Pfennig A. · Charité-University Medicine Berlin, Campus Charité Mitte (CCM), Department of Psychiatry and Psychotherapy, Berlin, Germany. · Epilepsia. · Pubmed #15968806 No free full text.

Abstract: Bipolar, or manic-depressive, disorders are frequent and severe mental illnesses associated with considerable morbidity and mortality. Epilepsy and bipolar disorder could probably share some aspects of pathophysiology because manic as well as depressive symptoms are seen in patients with seizures, and a number of antiepileptic drugs are effectively used in the acute and prophylactic treatment of bipolar disorder. Epidemiologic research suggests a dimensional composition of bipolar illness at the population level. Apart from the DSM-IV diagnostic features of bipolar I (mania and depression) and bipolar II (hypomania and depression), the concept of bipolar spectrum disorders comprises a range of bipolar conditions with less obvious manifestations with estimated lifetime prevalence rates ranging from 2.8 to 6.5%. Expanding the definition of bipolar II disorders shows that half of the patients currently diagnosed with a unipolar depressive episode could suffer from unrecognized bipolar II disorder, and about the same number of mild depressive patients could be minor bipolars. Research efforts to refine the diagnostic criteria of bipolar disorder aim at an earlier and complete recognition of the disease to provide appropriate pharmacological and nonpharmacological treatment early in the course of the illness to anticipate individual suffering, suicidal behavior, and increased socioeconomic costs for society. This article also discusses risk factors, comorbid conditions, course of illness, as well as the individual and socioeconomic impact of bipolar disorders. CONCLUSIONS: The findings suggest reconceptualizing bipolar illnesses as highly recurrent, malignant disorders that occur far more frequently than previously thought. Interdisciplinary knowledge transfer could help to increase our understanding of the pathophysiology of these disorders as well as provide grounds for better recognition and treatment of patients with manic and/or depressive symptoms.

Baethge C, Baldessarini RJ, Mathiske-Schmidt K, Hennen J, Berghöfer A, Müller-Oerlinghausen B, Bschor T, Adli M, Bauer M. · Department of Psychiatry, Harvard Medical School, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA. · J Clin Psychiatry. · Pubmed #15705002 No free full text.

Abstract: BACKGROUND: Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies. METHOD: In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression. RESULTS: Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%. CONCLUSION: Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

Bauer M, Alda M, Priller J, Young LT, Anonymous00102. · Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany. · Pharmacopsychiatry. · Pubmed #14677087 No free full text.

Abstract: Bipolar disorder is increasingly recognized as an illness that may progress to impairment in neurocognitive functioning and cell loss in cortical and limbic brain regions. Glutamatergic damage and/or damage due to high glucocorticoid levels that inhibit adult neurogenesis are likely contributing mechanisms. Drug treatments with possible neuroprotective effects are becoming increasingly important both clinically and as research tools. Mood stabilizing drugs and lithium in particular may act to prevent neuronal damage and tissue loss that may occur in the brain of patients with bipolar disorders. Lithium has been shown to exert neuroprotective effects in vitro and to stimulate neurogenesis in the hippocampus. Animal studies have demonstrated pharmacological effects of lithium suggestive of its role in neuroprotection, which range from reducing excitotoxicity through increased glutamate uptake, to regulation of a number of signal transduction intermediates such as myo-inositol, protein kinase C, phosphotidylinositol-3 kinase (PI-3K)/protein kinase B (Akt), ras-mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3alpha and -3beta and calcium. It remains to be established whether lithium treatment protects against possible cell damage in the same manner as it protects against recurrences of the illness. We propose to examine the effect of long-term lithium treatment on neurocognitive functioning of bipolar patients and the use of lithium in the treatment of chronic neuropsychiatric disorders.

Bschor T, Lewitzka U, Sasse J, Adli M, Köberle U, Bauer M. · Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany. · Pharmacopsychiatry. · Pubmed #14677084 No free full text.

Abstract: For now more than 50 years, lithium has been the gold standard for the pharmacologic treatment of bipolar disorder. However, its utility is not restricted to acute mania and prophylactic treatment of bipolar disorder. A relatively new indication for its use is the addition to an antidepressant in the acute treatment phase of unipolar major depression. To date, this treatment approach called lithium augmentation is the best-documented approach in the treatment of refractory depression. In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment. In a recent double-blind, placebo-controlled trial, lithium augmentation has demonstrated to also be effective in the continuation treatment phase to prevent early relapses. From animal studies there is robust evidence that lithium augmentation increases serotonin (5-HT) neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. In contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants, neuroendocrine studies on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined DEX/CRH test. Here we review new data on the efficacy and mechanism of action of lithium augmentation.

Bauer M, London ED, Silverman DH, Rasgon N, Kirchheiner J, Whybrow PC. · Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany. · Pharmacopsychiatry. · Pubmed #14677082 No free full text.

Abstract: The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

Baethge C, Tondo L, Bratti IM, Bschor T, Bauer M, Viguera AC, Baldessarini RJ. · Consolidated Department of Psychiatry, Harvard Medical School, Bipolar and Psychotic Disorders Program, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts, USA. · Can J Psychiatry. · Pubmed #12971014 No free full text.

Abstract: OBJECTIVE: To analyze new and reviewed findings to evaluate relations between treatment response and latency from onset of bipolar disorder (BD) to the start of mood-stabilizer prophylaxis. METHOD: We analyzed our own new data and added findings from research reports identified by computerized searching. RESULTS: We found 11 relevant studies, involving 1485 adult patients diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years (SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness intensity and shorter treatment latency were closely associated, resulting in a greater apparent reduction in morbidity with earlier treatment. However, this finding was not sustained after correction for pretreatment morbidity, and treatment latency did not predict morbidity during treatment. Therefore, assessments based on improvement with treatment, or without correction for pretreatment morbidity, can be misleading. CONCLUSIONS: Available evidence does not support the proposal that delayed prophylaxis may limit response to prophylactic treatment in BD and related disorders.

Sachs GS, Thase ME, Otto MW, Bauer M, Miklowitz D, Wisniewski SR, Lavori P, Lebowitz B, Rudorfer M, Frank E, Nierenberg AA, Fava M, Bowden C, Ketter T, Marangell L, Calabrese J, Kupfer D, Rosenbaum JF. · Partners Bipolar Treatment Center, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. · Biol Psychiatry. · Pubmed #12788248 No free full text.

Abstract: The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to a National Institute of Mental Health initiative seeking a public health intervention model that could generate externally valid answers to treatment effectiveness questions related to bipolar disorder. STEP-BD, like all effectiveness research, faces many design challenges, including how to do the following: recruit a representative sample of patients for studies of readily available treatments; implement a common intervention strategy across diverse settings; determine outcomes for patients in multiple phases of illness; make provisions for testing as yet undetermined new treatments; integrate adjunctive psychosocial interventions; and avoid biases due to subject drop-out and last-observation-carried-forward data analyses. To meet these challenges, STEP-BD uses a hybrid design to collect longitudinal data as patients make transitions between naturalistic studies and randomized clinical trials. Bipolar patients of every subtype with age >/= 15 years are accessioned into a study registry. All patients receive a systematic assessment battery at entry and are treated by a psychiatrist (trained to deliver care and measure outcomes in patients with bipolar disorder) using a series of model practice procedures consistent with expert recommendations. At every follow-up visit, the treating psychiatrist completes a standardized assessment and assigns an operationalized clinical status based on DSM-IV criteria. Patients have independent evaluations at regular intervals throughout the study and remain under the care of the same treating psychiatrist while making transitions between randomized care studies and the standard care treatment pathways. This article reviews the methodology used for the selection and certification of the clinical treatment centers, training study personnel, the general approach to clinical management, and the sequential treatment strategies offered in the STEP-BD standard and randomized care pathways for bipolar depression and relapse prevention.

Bauer M, Unützer J, Pincus HA, Lawson WB, Anonymous00320. · Mental Health & Behavioral Sciences Service, Brown University, Providence, Rhode Island 02908-2799, USA. · Ment Health Serv Res. · Pubmed #12558008 No free full text.

Abstract: Manic-depressive (bipolar) disorder is a severe, relapsing mental illness that shares characterstics both with major depressive disorder and with serious mental illnesses such as schizophrenia. Like schizophrenia, it is a chronic disorder, and is treated primarily in the specialty mental health sector. Rates of appropriate treatment are low. Functional outcome is compromised for the majority of individuals who have this disorder. Societal costs are exceeded only by those for schizophrenia. Existing cost calculations likely underestimate societal costs because of underestimating functional impact and neglecting to account for the substantial proportion of individuals who are institutionalized outside of the health care system (e.g., in prison). Little is known as yet regarding manic-depressive disorder in historically underserved groups and in vulnerable groups such as the elderly. There are major lacunae with regard to this disorder in the grant portfolios of all federal agencies mandated to address the needs of Americans with serious mental illnesses. The authors in the context of the Wider NIMH Affective Disorders Workgroup propose several specific recommendations to address the needs of this costly and underresearched disorder.

Müller-Oerlinghausen B, Berghöfer A, Bauer M. · Department of Psychiatry, Research Group of Clinical Psychopharmacology, Freie Universität Berlin, Berlin, · Lancet. · Pubmed #11812578 No free full text.

Abstract: Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1.3 to 1.6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10-20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated. Lithium salts are the first choice long-term preventive treatment for bipolar disorder. They also possess well documented antisuicidal effects. Second choice prophylactic treatments are carbamazepine and valproate, although evidence of their effectiveness is weaker.

Bowden CL, Lecrubier Y, Bauer M, Goodwin G, Greil W, Sachs G, von Knorring L. · Department of Psychiatry, The University of Texas, Health Science Center, 7703 Floyd Curl Drive, 78284-7792, San Antonio, TX, USA. · J Affect Disord. · Pubmed #11121827 No free full text.

Abstract: The progressive, episodic and chronic nature of bipolar disorder dictates the need for lifelong pharmacological maintenance treatment in the majority of patients. Prophylaxis should be considered after a single episode of severe mania or after more than one episode of hypomania in bipolar II disorder, although some clinicians now consider an episode of either sufficient to warrant maintenance therapy. Lithium is efficacious as maintenance therapy, but is not as highly effective as early studies initially suggested (abrupt discontinuation of lithium probably increased placebo relapse figures). Rates of premature discontinuation of lithium are high. Divalproex sodium is used frequently in the USA and Canada for long-term treatment for bipolar disorder but an insufficient number of controlled trials have been published to assess adequately its role. Carbamazepine is also employed in maintenance treatment. Randomized studies indicate it is superior to placebo but somewhat less effective than lithium. Augmentation of any of these drugs with another mood stabilizer, an antipsychotic, or electroconvulsive therapy appears to be effective, although there are few controlled studies. Design issues that need consideration in order to achieve meaningful data are discussed. A severe manifestation of bipolar disorder is rapid cycling. It is often induced by antidepressants, although this association frequently goes unrecognized. Patients with a rapid cycling course of illness are difficult to treat effectively. Although rapid cycling is often associated with poor response to lithium, there have been no randomized, controlled treatment studies. Based on open studies and expert panel recommendations, the International Exchange on Bipolar Disorder (IEBD) recommended initial treatment with divalproex sodium, with subsequent addition of other mood stabilizers, antipsychotics or thyroid supplementation as necessary. Combination treatments are frequently required for optimal response in these patients.

Bauer M, Ströhle A. · Psychiatrische Klinik und Poliklinik, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin. · Nervenarzt. · Pubmed #10434258 No free full text.

Abstract: Lithium is still regarded as the first choice substance in the prophylactic treatment of bipolar disorder. However, approximately one third of patients with a "classic" course of bipolar affective disorder do not adequately respond to lithium prophylaxis. The introduction of carbamazepine and valproic acid allowed a more differential syndrome- and course-orientated approach to the prophylactic treatment of bipolar disorder for the first time. However, about 10 to 20 percent of patients still remain refractory to standard regimes. Therefore, criteria for resistance to prophylactic treatment have to be further established. It has been suggested that at least two adequate trials of more than 12 months duration with sufficient drug blood levels have to be performed before refractoriness should be assumed. A severe subtype of affective disorder with poor response to lithium and other treatment approaches is a rapid cycling course which is characterised by at least four affective episodes per year. Here we present an overview of the currently available alternatives for prophylactic treatment, i.e. anticonvulsants, combination treatment, adjunctive thyroxine, calcium channel blockers, and more experimental approaches for treating refractory bipolar disorder patients. Suggestions for optimizing the prophylactic treatment of bipolar disorder are summarized in an algorithm.

Berghöfer A, Alda M, Adli M, Baethge C, Bauer M, Bschor T, Glenn T, Grof P, Müller-Oerlinghausen B, Rybakowski J, Suwalska A, Pfennig A. · Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, 10098 Berlin, Germany. · J Clin Psychiatry. · Pubmed #19026269 No free full text.

Abstract: OBJECTIVE: Poor response to long-term lithium treatment has been reported to be associated with atypical features of bipolar disorder. The purpose of this study was to investigate the influence of atypical symptoms on the effectiveness and stability of long-term lithium treatment in a prospective, multicenter cohort of bipolar patients in a naturalistic setting. METHOD: Patients were initially selected according to International Classification of Diseases, 8th Revision, criteria for bipolar disorder and required long-term treatment. Their diagnoses were reconfirmed according to DSM-IV upon its publication. They were prospectively followed for an approximately 20-year period ending in 2004 in 5 centers participating in the International Group for the Study of Lithium-Treated Patients. Examinations included a comprehensive psychiatric evaluation, an assessment of typical and atypical features on an 8-item scale, and an evaluation of clinical course using the morbidity index. Unbalanced repeated-measures regression models with structured covariance matrices were used to assess the extent to which the morbidity index was influenced by atypical symptoms, duration of treatment, and pretreatment features. RESULTS: A total of 242 patients were followed for a mean period of 10 years. In 142 patients, the number of typical features was greater than the number of atypical features, whereas in 100 patients the number of atypical features was greater than or equal to the number of typical features. The mean morbidity index remained stable over a period of 20 years in both groups of patients and was not significantly associated with the presence of atypical features, the duration of lithium treatment, the number or frequency of episodes, or latency from the onset of bipolar disorder to the start of lithium treatment. CONCLUSION: Our study suggests that long-term response to lithium maintenance treatment is stable both in patients with typical and in patients with atypical features. The predominance of either typical or atypical features did not result in different responses to long-term lithium treatment in this sample of bipolar patients.

Bauer M, London ED, Rasgon N, Berman SM, Frye MA, Altshuler LL, Mandelkern MA, Bramen J, Voytek B, Woods R, Mazziotta JC, Whybrow PC. · Neuropsychiatric Institute & Hospital, University of California Los Angeles , CA, USA. · Mol Psychiatry. · Pubmed #15724143 No free full text.

Abstract: Supplementation of standard treatment with high-dose levothyroxine (L-T(4)) is a novel approach for treatment-refractory bipolar disorders. This study tested for effects on brain function associated with mood alterations in bipolar depressed patients receiving high-dose L-T(4) treatment adjunctive to ongoing medication (antidepressants and mood stabilizers). Regional activity and whole-brain analyses were assessed with positron emission tomography and [(18)F]fluorodeoxyglucose in 10 euthyroid depressed women with bipolar disorder, before and after 7 weeks of open-label adjunctive treatment with supraphysiological doses of L-T(4) (mean dose 320 microg/day). Corresponding measurements were acquired in an age-matched comparison group of 10 healthy women without L-T(4) treatment. The primary biological measures were relative regional activity (with relative brain radioactivity taken as a surrogate index of glucose metabolism) in preselected brain regions and neuroendocrine markers of thyroid function. Treatment-associated changes in regional activity (relative to global activity) were tested against clinical response. Before L-T(4) treatment, the patients exhibited significantly higher activity in the right subgenual cingulate cortex, left thalamus, medial temporal lobe (right amygdala, right hippocampus), right ventral striatum, and cerebellar vermis; and had lower relative activity in the middle frontal gyri bilaterally. Significant behavioral and cerebral metabolic effects accompanied changes in thyroid hormone status. L-T(4) improved mood (remission in seven patients; partial response in three); and decreased relative activity in the right subgenual cingulate cortex, left thalamus, right amygdala, right hippocampus, right dorsal and ventral striatum, and cerebellar vermis. The decrease in relative activity of the left thalamus, left amygdala, left hippocampus, and left ventral striatum was significantly correlated with reduction in depression scores. Results of the whole-brain analyses were generally consistent with the volume of interest results. We conclude that bipolar depressed patients have abnormal function in prefrontal and limbic brain areas. L-T(4) may improve mood by affecting circuits involving these areas, which have been previously implicated in affective disorders.

Baethge C, Gruschka P, Smolka MN, Berghöfer A, Bschor T, Müller-Oerlinghausen B, Bauer M. · Consolidated Department of Psychiatry, Harvard Medical School, the Bipolar and Psychotic Disorders Program, McLean Division of Massachusetts General Hospital, Belmont, Mass 02478-9106, USA. · J Psychiatry Neurosci. · Pubmed #14517579 links to  free full text

Abstract: OBJECTIVE: To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. METHODS: In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. OUTCOME MEASURES: Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-Index during prophylaxis and time to first recurrence after initiation of lithium treatment. RESULTS: During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p<0.001; 52 d/yr less; 95; CI 31-73 d) and a low Morbidity-Index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n=4) or a lack of efficacy (n=2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. CONCLUSIONS: The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants.

Baethge C, Smolka MN, Gruschka P, Berghöfer A, Schlattmann P, Bauer M, Altshuler L, Grof P, Müller-Oerlinghausen B. · Klinik für Psychiatrie und Psychotherapie, Freie Universität Berlin, Berlin, Germany. · Acta Psychiatr Scand. · Pubmed #12662248 No free full text.

Abstract: OBJECTIVE: This study investigated the impact of latency (the time between illness onset and initiation of prophylactic treatment) on the outcome of prophylaxis in bipolar disorders. METHOD: The effect of prophylaxis delay (latency) on the course of illness was assessed in 147 patients. Dependent variables were: reduction of days spent in the hospital (prior to vs. during prophylaxis), time to first recurrence, and Morbidity-Index during prophylaxis (lithium or carbamazepine). Latency and other independent variables were tested using a multivariate approach. RESULTS: Latency (9.3 years on average) had no significant effect on the subsequent response. Illness severity prior to prophylaxis, however, did predict the relative response. The course of illness during treatment could not be predicted by any one factor. CONCLUSION: The delay in initiating prophylaxis appears to have no influence on prophylaxis outcome. Instead, those whose illness was more severe were treated earlier and these patients subsequently showed a relatively greater response. If severity is not controlled for as part of the analysis, latency may be mistaken as an important predictor for response.