Depression: Bauer M

Bauer M, Bschor T, Pfennig A, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00106. · University Hospital Carl Gustav Carus, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany. · World J Biol Psychiatry. · Pubmed #17455102 No free full text.

Abstract: These practical guidelines for the biological treatment of unipolar depressive disorders in primary care settings were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). They embody the results of a systematic review of all available clinical and scientific evidence pertaining to the treatment of unipolar depressive disorders and offer practical recommendations for general practitioners encountering patients with these conditions. The guidelines cover disease definition, classification, epidemiology and course of unipolar depressive disorders, and the principles of management in the acute, continuation and maintenance phase. They deal primarily with biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy).

Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00267. · University of California Los Angeles (UCLA), Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, USA. · World J Biol Psychiatry. · Pubmed #12479080 No free full text.

Abstract: These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with the biological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Bauer M. · No affiliation provided · World J Biol Psychiatry. · Pubmed #17455101 No free full text.

This publication has no abstract.

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.

Storch A, Ebersbach G, Fuchs G, Jost WH, Odin P, Reifschneider G, Bauer M. · Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus, Dresden. · Fortschr Neurol Psychiatr. · Pubmed #19012223 No free full text.

Abstract: Non-motor symptoms, such as psychiatric symptoms and autonomic dysfunction, are common co-morbid conditions in Parkinson's disease (PD) and major contributors to poor quality of life and disability. Within the group of neuropsychiatric conditions, depressive symptoms are the most common condition. Despite their frequency and importance, depressive symptoms can be difficult to assess and diagnose and thus depression in PD is frequently unrealized. Diagnostic challenges include the overlap of depressive symptoms with motor and non-motor symptoms of PD, such as dementia and apathy. Furthermore, there are no definite standards to assess and diagnose depression in PD leading also to the lack of exact data on the epidemiology of this non-motor symptom in PD. Depending on the diagnostic test and the study design the prevalence of depression in PD is reported between 7 and 72% of PD patients with approximately 40% in most cross-sectional studies. In contrast, the pathogenesis and long-term course of depression in PD remain elusive. Current hypothesis, however, includes that depressive symptoms are part of the core condition of PD when regarded as an entity. The present review summarizes the current knowledge on epidemiology, pathogenesis and diagnosis of depression in PD and proposes on this data base a standard procedure for screening and diagnosis of depressive symptoms in PD.

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.

Pfennig A, Littmann E, Bauer M. · Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Mitte, Berlin, Germany. · J Neuropsychiatry Clin Neurosci. · Pubmed #18070839 links to  free full text

Abstract: In a substantial percentage of patients, mood disorders are accompanied by persistent neurocognitive impairment. Elderly patients with dementia often suffer from depression. Neurocognitive tests and imaging are increasingly used to complement diagnostics. Tests assessing memory, attention, executive functions, and visuospatial abilities might help to distinguish mood disorder patients who can be expected to develop dementia from those who will not. This review presents a summary of knowledge on neurocognitive profiles differentiating impairment in mood disorders and dementia. Ideas on pathophysiological causation and progression are translated into recommendations for patient management.

Pilhatsch M, Bauer M. · Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden. · Psychiatr Prax. · Pubmed #17786884 No free full text.

Abstract: OBJECTIVE: A systematic review on empirical results of current guidelines and recommendations with focus on efficacy and tolerability of antidepressant pharmacological treatment options. METHODS: A critical, systematic evaluation of peer reviewed surveys, meta-analyses and guidelines is provided with the focus on evidence based consequences for the psychiatric clinical practice in the treatment of major depressive episodes. RESULTS: Most of modern and classic antidepressants have not proved differences in studies regarding comparative effectiveness. In contrast clinical decisions are increasingly guided by differences of tolerability, which are clearly documented in the current literature. Many algorithm based treatment options exist to face the common problem of treatment resistance. CONCLUSIONS: The multitude of effective antidepressant options provides an individual and patient orientated treatment. To achieve an optimal utilization of these options, an orientation on multi-step treatment plans is useful.

Bschor T, Lewitzka U, Pfennig A, Bauer M. · Abteilung für Psychiatrie und Psychotherapie, Jüdisches Krankenhaus Berlin, Heinz-Galinski-Strasse 1, 13347 Berlin. · Nervenarzt. · Pubmed #17458527 No free full text.

Abstract: Twenty-five years ago the research group of the Canadian psychiatrist de Montigny reported treating antidepressant-refractory depressive patients successfully by adding lithium to their antidepressant. The report, published in 1981 as an open-label uncontrolled observation of only eight patients, falls short of today's methodological standards, but the treatment method, subsequently known as lithium augmentation, nonetheless was to change profoundly the pharmacological strategies for depressive disorders. The story of its development is remarkable, starting with a strictly theoretical idea conceived by Montigny and his colleagues after animal experiments in the 1970s had revealed that pretreatment with an antidepressant over several weeks led to sensitization of central nervous serotonin receptors. The team postulated that the proserotonergic characteristics of lithium, which had been systematically used as a psychotropic drug since 1949, could thus be used specifically to stimulate these receptors. Lithium augmentation demonstrated its effectiveness in the 1980s and 1990s, first in open-label and later in randomized and placebo-controlled studies. In the late 1990s studies aimed at optimizing its clinical application indicated that lithium augmentation must be administered for at least 2 weeks, with lithium serum levels within the range established for prophylactic treatment and assuming patient response, and that the combination of lithium and antidepressant must be continued as a maintenance therapy for 6 to 12 months. Research has yet to clarify how lithium augmentation actually works. Current results show that in addition to the idea postulated by Montigny, lithium could also have an activating effect on the cortisol axis. Thanks to the sound body of evidence which has accrued in the meantime, lithium augmentation is recommended in most guidelines and treatment algorithms as a main strategy for patients who do not respond to antidepressant monotherapy.

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.

Bschor T, Bauer M. · Department of Psychiatry and Psychotherapy, Jewish Hospital Berlin, Heinz-Galinski-Str. 1, D-13347 Berlin, Germany. · Curr Pharm Des. · Pubmed #16918427 No free full text.

Abstract: Lithium augmentation refers to the addition of lithium to an antidepressant in the acute treatment phase of patients with depressive episodes who have failed to respond satisfactorily to treatment with antidepressant monotherapy. This article reviews the clinical evidence and hypotheses on the mode of action of lithium augmentation. For this purpose, studies were identified by searching Medline and by scanning the references of published reviews and standard textbooks. With regard to efficacy, 28 prospective studies (with a total of 838 depressed patients) were identified. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation. A recent meta-analysis including only double-blind, placebo-controlled trials (N = 9) provided firm evidence that lithium augmentation has a statistically significant effect on response rate compared to placebo, and showed that lithium augmentation should be administered for at least 2 weeks to allow assessment of the patient's response. A recent double-blind, placebo-controlled trial revealed that responders to lithium augmentation should be maintained on the lithium-antidepressant combination for a minimum of 12 months. From animal studies there is robust evidence that lithium augmentation increases serotonin (5-HT) neurotransmission, possibly through a synergistic action of lithium and the antidepressant on brain 5-HT pathways. Neuroendocrine studies in humans 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 dexamethasone/CRH test. These results are in contrast to the established decline of HPA system activity during treatment with antidepressants. In conclusion, lithium is the foremost and most well-documented augmentation strategy in 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.

Adli M, Bauer M, Rush AJ. · Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany. · Biol Psychiatry. · Pubmed #16769294 No free full text.

Abstract: BACKGROUND: Treatment algorithms and collaborative-care systems are systematic treatment approaches that are designed to improve outcomes by enhancing the quality of care. During the last decade, algorithm research has evolved as a new branch of clinical research that evaluates the clinical and economic impact of algorithm-guided treatment in primary and psychiatric care of patients with depressive disorders. METHODS: This article discusses the rationale of algorithm development, their risks and limitations, and important elements in their implementation in clinical practice. It further reviews the available studies that have evaluated algorithm-guided treatment for depression. RESULTS: Recent studies show that compared with treatment as usual, the use of algorithms and collaborative-care approaches in the care of depressed patients enhances treatment outcomes by modifying practice procedures and treatment processes. CONCLUSIONS: Treatment algorithms and collaborative-care systems clearly increase the efficacy of applied treatments in the care of depressed patients. However, to what extent the enhanced outcomes are a result of diligent measurement-based care or of the specific treatment steps that are used remains to be resolved. Valid clinical or pharmacogenetic predictors of response are needed to further tailor specific algorithms to individual patients.

Bauer M, Möller HJ, Schneider E. · Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, D-10117 Berlin, Germany. · Expert Opin Pharmacother. · Pubmed #16503814 No free full text.

Abstract: Antidepressants that inhibit the re-uptake of serotonin and noradrenaline might offer a chance to reduce the multiple symptoms of depression, as both serotonin and noradrenaline seem to be responsible for the emotional and physical symptoms of depression. The potential superiority of a dual mechanism of action has already been demonstrated in a number of clinical trials. Duloxetine, a novel dual acting, selective serotonin and noradrenaline-re-uptake inhibitor, has demonstrated high remission rates and good efficacy on physical symptoms, especially painful physical symptoms of depression. The results from studies in diabetic neuropathic pain provide further evidence of the effect of duloxetine on pain, independent of its effect on depression. Therefore, duloxetine provides an alternative to current therapeutic options in the treatment of the different symptoms of depression.

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.

Adli M, Baethge C, Heinz A, Langlitz N, Bauer M. · Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #15868067 No free full text.

Abstract: BACKGROUND: Maximizing the dose of antidepressants is widely recommended in cases of non-response to medium-dose treatment. However, scientific evidence supporting high-dose treatment is scarce. Systematic studies comparing dose escalation with alternative strategies for refractory depression (i. e. augmentation or change of compound) are lacking. The aim of this publication is to review available direct and indirect evidence concerning dose increase of antidepressants after a medium-dose trial has failed. METHOD: We performed a systematic literature search of Medline (1966-2003) and reviewed studies and publication references for available evidence. DATA SOURCES AND STUDY SELECTION: Studies of the following types were included: 1) dose increase studies in treatment refractory patients, 2) comparative dose studies, 3) therapeutic drug monitoring studies. RESULTS: Available data suggest differential efficacy of various pharmacological classes at more than medium-dosage. Direct evidence shows no increase of efficacy with high-dose selective serotonin reuptake inhibitor (SSRI) treatment; however, indirect evidence suggests enhanced therapeutic efficacy with high-dose tricyclic antidepressants. Few clinical data show ultra-high-dose treatment with the irreversible monoamine-oxidase-(MAO-) inhibitor tranylcypromine to be effective for refractory depression. Data concerning other selective compounds are insufficient to allow any definitive conclusion on the benefit of high-dose treatment. CONCLUSIONS: Based on available data highdose antidepressant treatment of patients refractory to medium-dose treatment is recommended for tricyclic compounds but not for SSRI. Some data suggest beneficial efficacy of ultra-high doses of the irreversible MAOI tranylcypromine. Research on other substance groups is limited and inconclusive. Prospective studies comparing dose escalation with alternative strategies for treatment of non-responding patients are needed.

Kirchheiner J, Sasse J, Roots I, Brockmöller J, Bauer M. · Institut für Klinische Pharmakologie, Universitätsmedizin Berlin. · Nervenarzt. · Pubmed #15864514 No free full text.

Abstract: The pharmacokinetics and effect of antidepressants are influenced by genetic factors. Modern methods of genotyping allow fast and inexpensive identification of genetic variants and thus can be used in clinical diagnostics to improve the tolerance to drug therapy. Numerous studies have investigated the significance of genetic variants in drug-metabolizing enzymes, drug and natural substrate transporters, neurotransmitter receptors, and molecules involved in signal transduction. While the interindividual differences in oral clearance, half-life, and bioavailability caused by genetic variants in the cytochrome P450 liver enzymes can be overcome by individual adjustment of dosage according to certain genotypes, the effects of genetic variants in antidepressive target structures are more difficult to translate into clinical recommendations. This article gives an overview of the currently available literature and points to situations in which the determination of pharmacogenetic variants might change drug therapy or therapeutic strategies for the individual patient. Dose adjustments for common antidepressant drugs based upon differences in pharmacokinetic parameters caused by genetic variability will be given.

Kirchheiner J, Bertilsson L, Bruus H, Wolff A, Roots I, Bauer M. · Institute of Clinical Pharmacology, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany. · Pharmacopsychiatry. · Pubmed #14677085 No free full text.

Abstract: Antidepressant drug therapy is characterized by a high rate of therapeutic failure. There is increasing evidence that genetic factors are contributing to the inter-individual variability in antidepressant drug response. Genetic variability is described in both the pharmacokinetic part of drug action as well as in pharmacodynamic structures mediating drug effects. Genetic polymorphisms in drug metabolizing enzymes are well characterized and have large effects on oral clearances or elimination half-lives of antidepressant drugs. These differences can be compensated by adapting the individual dose to genotype in addition to other factors such as gender, weight, age, liver and kidney function. On the part of drug action, genetic variability is described in molecular structures of antidepressant effects. Several studies on response of antidepressants have revealed influences of polymorphisms in neurotransmitter receptors and transporters changing sensitivity of patients to treatment with antidepressants; however, results were often contradictory. A pharmacogenomic approach to individualize antidepressant drug treatment is recommended to be based on several levels: 1) identifying and validating the candidate genes involved in drug-response; 2) providing therapeutic guidelines; and 3) developing a pharmacogenetic test-system for bedside-genotyping.

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.

Adli M, Rush AJ, Möller HJ, Bauer M. · Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany. · Pharmacopsychiatry. · Pubmed #14677083 No free full text.

Abstract: Medication algorithms for the treatment of depression are designed to optimize both treatment implementation and the appropriateness of treatment strategies. Thus, they are essential tools for treating and avoiding refractory depression. Treatment algorithms are explicit treatment protocols that provide specific therapeutic pathways and decision-making tools at critical decision points throughout the treatment process. The present article provides an overview of major projects of algorithm research in the field of antidepressant therapy. The Berlin Algorithm Project and the Texas Medication Algorithm Project (TMAP) compare algorithm-guided treatments with treatment as usual. The Sequenced Treatment Alternatives to Relieve Depression Project (STAR*D) compares different treatment strategies in treatment-resistant patients.

Bauer M, Adli M, Baethge C, Berghöfer A, Sasse J, Heinz A, Bschor T. · Department of Psychiatry and Psychotherapy, Charité University Hospital, Humboldt-University at Berlin, Schumannstr. 20/21, 10117 Berlin, Germany. · Can J Psychiatry. · Pubmed #12971013 No free full text.

Abstract: OBJECTIVE: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. METHOD: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. RESULTS: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. CONCLUSIONS: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

Bauer M, Forsthoff A, Baethge C, Adli M, Berghöfer A, Döpfmer S, Bschor T. · Klinik fur Psychiatrie und Psychotherapie, Charite Campus Mitte Humboldt-Universitat zu Berlin, Schumannstr. 20-21, 10117, Berlin, Germany, · Eur Arch Psychiatry Clin Neurosci. · Pubmed #12904977 No free full text.

Abstract: Lithium has been used to augment the efficacy of antidepressant medications for more than 20 years. The present study examines whether evidence exists to support the clinical efficacy of lithium augmentation in refractory, treatment resistant depression. Studies were identified by searching Medline (1980 to August 2002) and by scanning the references of published reviews and standard textbooks. Studies were selected if they were open-labeled or double-blind, placebo-controlled or comparator trials that involved patients who had not responded to conventional antidepressants. 27 prospective studies were identified that included a total of 803 depressed patients displaying the following designs: 10 double-blind, placebo-controlled trials, 2 randomized, double-blind comparator trials, 2 randomized, open comparator trials, and 13 open-label trials. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45% and in the placebo group 18% (p<0.001). Summarizing all open and controlled studies, approximately 50% of patients responded to lithium augmentation within 4 weeks. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression.Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants.

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.

Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00268. · Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles (ULCA), 300 UCLA Medical Plaza, Suite 2330, Los Angeles, CA 90095, USA. · World J Biol Psychiatry. · Pubmed #12479086 No free full text.

Abstract: These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). This first part of the guidelines covers disease definition, classification, epidemiology and course of unipolar depressive disorders, as well as the management of the acute and continuation-phase treatment. These guidelines are primarily concerned with the biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.