Depression: Berk M

Malhi GS, Adams D, Porter R, Wignall A, Lampe L, O'Connor N, Paton M, Newton LA, Walter G, Taylor A, Berk M, Mulder RT, Anonymous00017, Anonymous00018, Anonymous00019. · CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, University of Sydney, NSW, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #19356154 No free full text.

Abstract: OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.

Berk M, Dodd S. · No affiliation provided · Hum Psychopharmacol. · Pubmed #15981307 No free full text.

This publication has no abstract.

Berk M, Dodd S. · No affiliation provided · Hum Psychopharmacol. · Pubmed #15614839 No free full text.

This publication has no abstract.

Berk M. · Melbourne University, Barwon Health and the Geelong Clinic, Mental Health Research Institute, and Orygen Research Centre, Victoria. · Aust Fam Physician. · Pubmed #19458799 links to  free full text

Abstract: BACKGROUND: Sleep disorders are particularly common in the primary care setting, and are intimately interlinked with depression. OBJECTIVE: This article aims to review the relationship between sleep and depression, with an emphasis on the foundation and clinical salience of this relationship. DISCUSSION: Depression is the most common cause of insomnia, and insomnia is highly prevalent in depression. This association has a well characterised physiological foundation. Sleep disorder in depression has prognostic and therapeutic implications. Residual insomnia after remission of depression is predictive of relapse, and prominent insomnia predicts a poorer treatment outcome in depression. Evidence based management involves integrating both pharmacological and behavioural strategies; the latter includes sleep hygiene and regulating diurnal rhythms.

Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Berk M. · Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, Geelong, Vic. Australia. · Psychother Psychosom. · Pubmed #18852498 No free full text.

Abstract: BACKGROUND: There are data to suggest low bone mineral density is disproportionately prevalent among those with psychiatric disorders. This paper aims to review the current evidence on the relationship between depression and bone mineral density, and identify potential mechanisms. METHODS: Relevant sources were identified from the Pubmed and Web of Science (ISI) databases from the first relevant publication in 1994 to the present, 2007, using a combination of key words and terms including depression, major depressive disorder, osteoporosis, bone mineral density, hypothalamic-pituitary-adrenal axis, cortisol, cytokines, leptin, antidepressants, selective serotonin reuptake inhibitors, smoking, alcohol, physical activity and diet. Reference lists of chosen articles were further reviewed for associated publications. RESULTS: The possible association between psychiatric illness, in particular depression, and osteoporosis has been the subject of a growing body of research yielding various findings, although most identify some effect on bone. In addition to medication-related processes and/or modifiable lifestyle factors associated with mood disturbances, endocrine and immune alteration secondary to depression may play a pathogenetic role in bone metabolism. CONCLUSIONS: Additional longitudinal studies, with the advantage of temporal sequencing, remain to be conducted, as well as research into potential mechanisms surrounding the association. Nevertheless, the current findings are of clinical relevance, given the health burden of both depression and osteoporosis.

Dodd S, Berk M. · Department of Clinical & Biomedical Sciences, University of Melbourne, Geelong, Australia. · Expert Rev Neurother. · Pubmed #18759541 No free full text.

Abstract: Antidepressant monotherapy is a first-line treatment for depression; however, not all sufferers will adequately respond to treatment. When treating a patient with treatment-resistant depression, the clinician needs to consider all factors which may contribute to an inadequate response to an antidepressant. These include accuracy of diagnosis and medication adherence, as well as the patient's personality, lifestyle, life events and social circumstances. If it is determined that treatment resistance is due to failure of efficacy of antidepressant monotherapy, then an augmentation strategy using an atypical antipsychotic may be considered. Treatment using olanzapine/fluoxetine combination (OFC) is one of many options. Four randomized, acute-phase trials have suggested OFC is useful for reducing Montgomery-Asberg Depression Rating Scale scores after inadequate response to antidepressant monotherapy. OFC has been useful at doses of olanzapine/fluoxetine 6/25, 6/50, 12/25 and 12/50 mg/day, with 1/5 mg/day suggested to be an ineffective dose. Treatment with OFC has been associated with some side effects, including weight gain and the metabolic syndrome, somnolence, dry mouth, increased appetite and headache. Treatment decisions therefore need to be made to balance the risks and benefits.

Ng F, Berk M, Dean O, Bush AI. · Department of Clinical and Biomedical Sciences, Barwon Health, University of Melbourne, Geelong, VIC, Australia. · Int J Neuropsychopharmacol. · Pubmed #18205981 No free full text.

Abstract: Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage. This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications. A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Preview, and Cochrane databases, with a time-frame extending to September 2007. The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants. For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial. Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data. Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.

Cassidy F, Yatham LN, Berk M, Grof P. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · Bipolar Disord. · Pubmed #18199232 No free full text.

Abstract: OBJECTIVE: To review issues surrounding the diagnosis and validity of bipolar manic states. METHODS: Studies of the manic syndrome and its diagnostic subtypes were reviewed emphasizing historical development, conceptualizations, formal diagnostic proposals, and validation. RESULTS: Definitions delineating mixed and pure manic states derive some validity from external measures. DSM-IV and ICD-10 diagnosis of bipolar mixed states are too rigid and less restrictive definitions can be validated. Anxiety is a symptom often overlooked in diagnosis of manic subtypes and may be relevant to the mixed manic state. The boundary for separation of mixed mania and depression remains unclear. A 'pure' non-psychotic manic state similar to Kraepelin's 'hypomania' has been observed in several independent studies. CONCLUSIONS: Issues surrounding diagnostic subtyping of manic states remain complex and the debates surrounding categorical versus dimensional approaches continue. To the extent that categorical approaches for mixed mania diagnosis are adopted, both DSM-IV and ICD-10 are too rigid. Inclusion of non-specific symptoms in definitions of mixed mania, such as psychomotor agitation, does not facilitate and may hinder the diagnostic separation of pure and mixed mania. The inclusion of a diagnostic seasonal specifier for DSM-IV, which is currently based on seasonal patterns for depression might be expanded to include seasonal patterns for mania. Boundaries between subtypes may be 'fuzzy' rather than crisp, and graded approaches could be considered. With the continued development of new tools, such as imaging and genetics, alternative approaches to diagnosis other than the purely symptom-centric paradigms might be considered.

Berk M, Hallam K, Lucas N, Hasty M, McNeil CA, Conus P, Kader L, McGorry PD. · Barwon Health, University of Melbourne, Geelong, VIC, Australia. · Med J Aust. · Pubmed #17908017 links to  free full text

Abstract: The early phases of bipolar disorders are difficult to diagnose and have specific treatment issues. The initial polarity of the illness is more commonly depressive, yet in counterpoint, mania is required for diagnosis; consequently, there is often a substantial delay in the initiation of appropriate therapy. There is good evidence that lithium in particular is most effective early in the illness course, and that its efficacy declines after multiple episodes. The notion of neuroprotection reflects this, and furthermore suggests that appropriate therapy may prevent the neurostructural and neurocognitive changes seen in the disorder. Inappropriate therapy may worsen the course of the illness. Patients with a first episode have specific psychosocial needs, and adherence to medication is relatively poor. There is a need for early identification, and to develop treatments and services applicable to the specific needs of this population.

Berk M, Dodd S, Kauer-Sant'anna M, Malhi GS, Bourin M, Kapczinski F, Norman T. · Department of Clinical and Biomedical Sciences, Barwon Health and The Geelong Clinic, University of Melbourne, Geelong, Victoria, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #17688462 No free full text.

Abstract: OBJECTIVE: Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder. METHOD: A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles. RESULTS: Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper. CONCLUSION: Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson's disease, administration of high-dose dopamine precursors can produce a 'maniform' picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development.

Stafford L, Berk M, Reddy P, Jackson HJ. · Department of Psychology, School of Behavioural Science, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Victoria, Australia. · J Psychosom Res. · Pubmed #17383491 No free full text.

Abstract: OBJECTIVE: This article reviews recent studies relating to the impact of depression and its treatment on the health-related quality of life (HRQOL) of patients with coronary artery disease (CAD). METHODS: Articles for the primary review were identified via MEDLINE and PsycINFO (1995-2006). RESULTS: Evidence suggests that depression has an aversive impact on the HRQOL of patients with stable CAD as well as on patients hospitalized for acute myocardial infarction and coronary artery bypass graft surgery. Unfortunately, there are few depression treatment studies in patients with CAD that make use of standardized HRQOL measures, but the limited evidence suggests that successful treatment has positive implications for HRQOL in these patients. The mechanisms through which depression impacts on HRQOL require further study but are likely to be behavioral. CONCLUSIONS: Depressive symptoms significantly undermine HRQOL in patients with CAD despite successful medical and surgical management. Although successful treatment of depression has not been shown to reduce mortality rates in patients with CAD, further study may find that the HRQOL benefits of such treatment are equally valuable.

Malhi GS, Berk M. · Psychological Medicine, Northern Clinical School, University of Sydney, NSW, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #17280577 No free full text.

Abstract: OBJECTIVE: To examine the evidence that dopamine (DA) dysfunction contributes to melancholic depression. METHOD: Database (EMBASE, PsychLit and MEDLINE) searches using relevant key words were conducted and citations were scrutinized. RESULTS: In this paper, we assume that the definition of melancholia is contingent upon the presence of psychomotor disturbance (PMD). In melancholic depression PMD comprises both a cognitive and motor component and DA is found to be important in both. DA neurotransmission modulates cognition in particular in attention, adaptation and motivational processes and has a pivotal role in motor function. CONCLUSION: DA is a credible aetiological candidate for the PMD in melancholic depression. However, melancholia needs first to be characterized both clinically and in terms of its pathophysiology. In this regard, illnesses such as bipolar depression and Parkinson's disease warrant consideration as they provide suitable models of both the cognitive and motor aspects of PMD, and hold the necessary markers to better define melancholia.

Ng F, Dodd S, Berk M. · University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, PO Box 281, Geelong, Victoria, Australia. · Expert Rev Neurother. · Pubmed #16831118 No free full text.

Abstract: It is estimated that between 60 and 80% of those with major depressive disorder do not achieve full symptomatic remission from first-line antidepressant monotherapy. Residual depressive symptoms substantially impair quality of life and add to the risk of recurrence. It is now clear that depression would benefit from more vigorous treatment, in order to ameliorate its disease burden. While there are established algorithms in situations of treatment resistance, the use of combination pharmacotherapy in unipolar depression is a relatively under-investigated area of treatment and may be an effective and tolerable strategy that maximizes the available resources. This paper reviews the current evidence for combination pharmacotherapy in unipolar depression and discusses its clinical applications.

Conus P, Berk M, McGorry PD. · Département Universitaire de Psychiatrie CHUV, Université de Lausanne, Treatment and Early Intervention Program for Psychosis (TIPP), Clinique de Cery, Prilly, Switzerland. · Aust N Z J Psychiatry. · Pubmed #16476146 No free full text.

Abstract: OBJECTIVE: To review available guidelines, explore treatment strategies currently applied, identify critical issues and propose direction for new developments. METHOD: Literature review based on Medline search and hand search of relevant literature. RESULTS: Pharmacological treatment of the early phase of bipolar disorders lacks specific guidelines. Mood stabilizers are often prescribed after many years of illness, antipsychotic medications are frequently prescribed and often for extensive periods of time, and adherence to medication is relatively poor. In addition, mania is frequently misdiagnosed, and there is limited knowledge on which to base identification of bipolar depression and identification of the initial prodrome to bipolar disorders. CONCLUSIONS: There is an urgent need for more research in the early phases of bipolar disorders to develop means to identify patients earlier and to develop approaches that would address the specific needs of this population in a more adequate manner.

Malhi GS, Berk M, Bourin M, Ivanovski B, Dodd S, Lagopoulos J, Mitchell PB. · Mood Disorder Unit, Black Dog Institute, Prince of Wales Hospital, Sydney, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #16104066 No free full text.

Abstract: OBJECTIVE: To assess the potential role of atypical antipsychotics as mood stabilizers.METHOD: A MedLine, PsychLIT, PubMed, and EMBASE literature search of papers published up to December 2004 was conducted using the names of atypical antipsychotics and a number of key terms relevant to bipolar disorder. Additional articles were retrieved by scrutinizing the bibliographies of review papers and literature known to the authors. Data pertinent to the objective was reviewed according to the various phases of bipolar disorder.RESULTS: The data is most substantive for the use of atypical antipsychotics in mania, to the extent that an argument for a class effect of significant efficacy can be made. This does not extend to bipolar depression, however, good data is now emerging for some agents and will need to be considered for each individual agent as it accumulates. As regards mixed states and rapid cycling the evidence is thus far sparse and too few maintenance studies have been conducted to make any firm assertions. However, with respect to long-term therapy the atypical antipsychotics do have clinically significant side-effects of which clinicians need to be aware.CONCLUSION: Based on the evidence thus far it is perhaps premature to describe the atypical antipsychotics as mood stabilizers. Individual agents may eventually be able to claim this label, however, much further research is needed especially with respect to maintenance and relapse prevention.

Berk M, Dodd S, Berk L. · Department of Clinical and Biomedical Sciences, Barwon Health, University of Melbourne, Geelong, Victoria, Australia. · Psychiatry Clin Neurosci. · Pubmed #15896214 No free full text.

Abstract: Recent evidence suggests that the prevalence of bipolar disorder is as much as fivefold higher than previously believed, and may amount to nearly 5% of the population, making it almost as common as unipolar major depression. It is, therefore, not unrealistic to assume that primary care or family physicians will frequently encounter bipolar patients in their practice. Such patients may present with a depressive episode, for a variety of medical reasons, for longer-term maintenance after stabilization, and even with an acute manic episode. Whatever the reason, a working knowledge of current trends in the acute and longer-term management of bipolar disorder would be helpful to the primary care physician. In addition, an understanding of important side-effects and drug interactions that occur with drugs used to treat bipolar disorder, which may be encountered in the medical setting, are paramount. This paper will attempt to review existing and emerging therapies in bipolar disorder, as well as their common drug interactions and side-effects.

Berk M, Dodd S, Malhi GS. · Barwon Health and The Geewong Clinic, Swanston Centre, PO Box 281, Geelong, Victoria 3220, Australia. · Aust N Z J Psychiatry. · Pubmed #15777356 No free full text.

Abstract: OBJECTIVE: To explore diagnostic and treatment issues concerning bipolar mixed states. METHOD: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed. RESULT: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression. CONCLUSIONS: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression. Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications. Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.

Berk M, Dodd S. · Department of Clinical and Biomedical Sciences, University of Melbourne, Swanston Centre, Geelong, Victoria, Australia. · Bipolar Disord. · Pubmed #15654928 No free full text.

Abstract: OBJECTIVES: To review the current knowledge of bipolar II disorder. METHODS: Literature was reviewed after conducting a Medline search and a hand search of relevant literature. RESULTS: Bipolar II disorder is a common disorder, with a prevalence of approximately 3-5%. Distinct clinical features of bipolar II disorder have been described. The key to diagnosis is the recognition of past hypomania, while depression is the typical presenting feature of the illness. This is responsible for a significant rate of missed diagnosis, and consequent management according to unipolar guidelines. It is unclear if bipolar II disorder is over-represented amongst resistant depression populations and if abrupt offset of antidepressant action is a phenomenon over represented in bipolar II disorder, reflecting induction of predominantly depressive cycling. A few mood-stabilizer studies available provide provisional suggestion of utility. A supportive role for psychosocial therapies is suggested, however, there is a sparsity of published studies specific to bipolar II disorder cohorts. A small number of short-term antidepressant trials have suggested efficacy, however, compelling long-term maintenance data is absent. CONCLUSIONS: An emerging literature on the specific clinical signature and management of the disorder exists, however, this is disproportionately small relative to the epidemiology and clinical significance of the disorder.

Berk M, Dodd S. · Department of Clinical and Biomedical Sciences, The University of Melbourne, Swanston Centre, PO Box 281, Geelong, VIC 3220, Australia. · Drugs. · Pubmed #15631544 No free full text.

Abstract: Bipolar disorder is a severe and recurrent disorder. Atypical antipsychotics have emerged as both an alternative and adjunct to conventional mood stabilisers. The manic phase of the illness is the best studied, and it appears that a class effect with regards to efficacy is present in both monotherapy and augmentation studies.Evidence for efficacy of atypical antipsychotics in depression is emerging. At this stage controlled data are available for both olanzapine and quetiapine. Maintenance data demonstrating efficacy are available for olanzapine. Atypical antipsychotics have utility in treating acute agitation and aggression in manic episodes of bipolar disorder. Subgroup analyses from trials treating manic phase bipolar disorder, and an open-label study of rapid cycling, have suggested that atypical antipsychotics may be useful for the treatment of mixed states and rapid cycling. Several studies have suggested that atypical antipsychotics may be useful in treatment-refractory episodes of bipolar disorder.The current available data suggest greater efficacy of the atypical antipsychotics in mania than in depression, although the data are fairly clear that induction of depression is not an issue with the atypical antipsychotics. A number of trials are underway that will hopefully address many of the questions still pending.

Berk M, Malhi GS, Mitchell PB, Cahill CM, Carman AC, Hadzi-Pavlovic D, Hawkins MT, Tohen M. · Barwon Health and The Geelong Clinic, Geelong, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #15330937 No free full text.

Abstract: OBJECTIVE: To briefly review the clinical and biological distinctions between unipolar and bipolar depression critiquing in particular currently available depression rating scales and discuss the need for a new observer-rated scale tailored to bipolar depression. METHOD: Relevant literature pertaining to the symptomatic differences between bipolar disorder and unipolar disorder as well as their measurement using existing assessment scales was identified by computerized searches and reviews of scientific journals known to the authors. RESULTS: Bipolar depression is distinct from unipolar depression in terms of phenomenology and clinical characteristics. These distinguishing features can be used to identify bipolarity in patients that present with recurrent depressive episodes. This is important because current self-report and observer-rated scales are optimized for unipolar depression, and hence limited in their ability to accurately assess bipolar depression. CONCLUSION: The development of a specific bipolar depression rating scale will improve the assessment of bipolar depression in both research and clinical settings and assist the development of better treatments and interventions.

Berk M. · Department of Psychiatry, University of the Witwatersrand Medical School, Parktown, South Africa. · Int Clin Psychopharmacol. · Pubmed #11110018 No free full text.

Abstract: The overlap between the depressive and anxiety disorders is extremely common. The introduction of the selective serotonin reuptake inhibitors (SSRIs) has, more than any other development, bridged the gap in terms of efficacy in both sets of disorders. A substantial body of data exists suggesting that the available SSRIs have substantial efficacy in anxiety symptoms co-occurring with depression. The clear utility of the SSRIs in disorders classified apart from depression is also established. Whilst panic disorder is the best studied, evidence on the efficacy of the SSRIs in disorders that previously did not attract much pharmacotherapeutic interest, such as social anxiety disorder and post-traumatic stress disorder is accumulating.

Yatham LN, Kennedy SH, Schaffer A, Parikh SV, Beaulieu S, O'Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Young AH, Alda M, Milev R, Vieta E, Calabrese JR, Berk M, Ha K, Kapczinski F. · Department of Psychiatry, University of British Columbia,2255 Wesbrook Mall, Vancouver, BC V6T 2A1, , Canada. · Bipolar Disord. · Pubmed #19419382 No free full text.

Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.

Kulkarni J, Berk M, Fitzgerald PB, de Castella AR, Montgomery W, Kelin K, Brnabic A, Granger RE, Dodd S. · Alfred Psychiatry Research Centre, The Alfred and Monash University, School of Psychology, Psychiatry & Psychological Medicine, Commercial Road, Melbourne VIC 3004, Australia. · J Affect Disord. · Pubmed #17889373 No free full text.

Abstract: BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, observational study of participants with bipolar I or schizoaffective disorder examining clinical, functional, and economic outcomes associated with naturalistic treatment. METHODS: Participants prescribed mood stabilisers were assessed using various measures, including the Young Mania Rating Scale (YMRS), 21-item Hamilton Depression Rating scale (HAMD21), Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), and the EuroQol instrument (EQ-5D). RESULTS: 240 participants were recruited from two sites. On average, participants were 41.8+/-12.7 years of age (mean+/-SD), 58.3% were female, and 73.3% had a diagnosis of bipolar I disorder at study entry. The majority of participants were moderately ill, with an average CGI-BP Overall score of 3.8+/-1.3. Most participants had subthreshold mania and depression symptoms, indicated by HAMD21 Total 13.4+/-8.6, CGI-BP Depression 3.2+/-1.3, YMRS Total 8.2+/-8.5 and CGI-BP Mania 3.0+/-1.6 average scores. For bipolar participants, 94.6% of hospitalisations for psychiatric treatment in the past 3 months were single admissions (vs. 65.2% for schizoaffective participants, p=.002). Bipolar participants rated their overall health state higher (EQ-5D scores: 68.2+/-18.8 vs. 61.6+/-22.7, p=.023), had a higher mean weekly wage ($500-$999, 21.3% vs. 6.3%), lower unemployment (22.2% vs. 48.4%), and higher romantic relationship status (47.1% vs. 26.6%). LIMITATIONS: The observational design and small sample size may have limited the causal relationships and generalisability within the current findings. CONCLUSIONS: Participants were characterised by social and occupational dysfunction at entry, but schizoaffective participants appeared to be more severely affected. Effective treatment is required to address both clinical and functional impairment.

Barbosa L, Berk M, Vorster M. · Department of Psychiatry, University of the Witwatersrand Medical School, Parktown, South Africa. · J Clin Psychiatry. · Pubmed #12716240 No free full text.

Abstract: BACKGROUND: Evidence of the antidepressant efficacy of lamotrigine is increasing, although there are no placebo-controlled trials of lamotrigine augmentation in depression. The aim of this study was to assess if augmentation with lamotrigine was superior to placebo in patients who were receiving fluoxetine for resistant major depressive episodes. METHOD: Twenty-three patients who had experienced at least 1 major depressive episode that was resistant to at least 1 prior trial of antidepressant therapy were selected. These patients were treated with fluoxetine, 20 mg/day, and concomitantly randomly assigned to receive either lamotrigine (N = 13) or placebo (N = 10) for 6 weeks. The dose of lamotrigine was titrated upward from 25 mg/day to 100 mg/day. Patients suffering from bipolar II disorder (N = 8) or from major depressive disorder (N = 15) (DSM-IV criteria) were enrolled, resulting in heterogeneity of the sample. The primary outcome measure was Hamilton Rating Scale for Depression score. Data were collected from 2000-2001. RESULTS: Lamotrigine was statistically superior to placebo on the Clinical Global Impressions scale at endpoint, both in absolute terms (mean +/- SD Clinical Global Impressions-Severity of Illness scores: lamotrigine, 2.15 +/- 1.28; placebo, 3.40 +/- 1.17; p =.0308) and using a responder analysis, with response defined as a Clinical Global Impressions-Improvement score of 2 or less (lamotrigine, 84.62% [N = 11]; placebo, 30.00% [N = 3]; p =.013). The effect of lamotrigine on Clinical Global Impressions scale scores was seen in both major depressive disorder and bipolar II disorder. Lamotrigine, however, failed to separate statistically from placebo on the Hamilton Rating Scale for Depression and Montgomery-Asberg Depression Rating Scale. This failure to differentiate on a primary outcome measure is essentially a negative study result. This result is most likely an artifact of the small sample size used and the resultant limited power of the study. CONCLUSION: The results of this trial add to the literature suggesting potential efficacy of the antidepressant profile of lamotrigine. In addition, this study points to a possible role of lamotrigine as an augmentation agent in depression.

Schutz G, Berk M. · Department of Psychiatry, University of the Witwatersrand Medical School, Johannesburg, South Africa. · Int Clin Psychopharmacol. · Pubmed #11552770 No free full text.

Abstract: The negative symptoms of schizophrenia remain a major clinical challenge. Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor. This study was a 6-week randomized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The trial failed to demonstrate any significant difference between the placebo and reboxetine groups on any of the outcome measures. This trial does not suggest that increased noradreneregic drive mediated by reuptake inhibition in patients taking dopamine antagonists is of therapeutic value in schizophrenia.