Anxiety Disorders: Berk M

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, 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.

Humble F, Berk M. · Barwon Health Mental Health, Swanston Centre, PO Box 281, Geelong, Victoria 3220, Australia. · Hum Psychopharmacol. · Pubmed #12923820 No free full text.

Abstract: The pharmacological management of violence and aggression is a common and substantial clinical dilemma in the emergency psychiatric situation. A literature search was conducted through PubMed and using the Cochrane Library. This was followed by a manual search of selected literature. Randomised controlled trials were sought that specifically addressed the acute situation, rather than the ongoing management of chronic conditions. There was a paucity of well-controlled data and insufficient evidence to support the use of many agents in emergency situations. Many studies had considerable limitations making comparison difficult. Efficacy data for a range of treatment options exists, including the use of classical and atypical anti-psychotic agents, benzodiazepines and combination therapies. Clinical risk, tolerability and environmental factors need to form part of a careful and considered judgement in the choice of treatment. Safety, tolerability and the potential for a positive experience are major considerations, thus paving the way for long term compliance.

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.

Stein DJ, Berk M, Els C, Emsley RA, Gittelson L, Wilson D, Oakes R, Hunter B. · Department of Psychiatry, University of Stellenbosch, Tygerberg, W Cape. · S Afr Med J. · Pubmed #10341825 No free full text.

Abstract: BACKGROUND: Social phobia, also known as social anxiety disorder, is a highly prevalent disorder with significant morbidity. Patients with social phobia frequently develop co-morbid psychiatric disorders such as depression and substance abuse, and the disorder impacts significantly on social and occupational functioning. It has been suggested that the selective serotonin reuptake inhibitors (SSRIs) are useful in the management of this disorder, but few controlled trials have been undertaken in this regard. There are also few data on the pharmacotherapy of social phobia in South Africa. METHODS: A double-blind randomised placebo-controlled multi-site flexible-dose trial of paroxetine was undertaken over 12 weeks among patients with a primary diagnosis of social phobia. Primary response measures were the Global Improvement item on the Clinical Global Impression scale (CGI) and mean change from baseline in the patient-rated Liebowitz Social Anxiety Scale (LSAS) total score. Ninety-three patients participated at 9 South African sites; their data are reported here. RESULTS: There was a significant drug effect on both the CGI Global Improvement score and the LSAS at 12 weeks. In addition, there was no significant difference in overall rate of adverse experiences between those on paroxetine and those on placebo. CONCLUSIONS: Paroxetine is both effective and safe in the acute treatment of social phobia. The findings here are consistent with those of previous controlled studies of the SSRIs as well as with previous work done in the USA on the use of paroxetine in the treatment of this disorder. Early diagnosis and treatment of social phobia should be encouraged. However, further research on long-term pharmacotherapy of social phobia is needed.

Plein H, Berk M. · Department of Experimental and Clinical Pharmacology, University of the Witwatersrand, Johannesburg, South Africa. · Eur Neuropsychopharmacol. · Pubmed #10082235 No free full text.

Abstract: Serotonin is implicated in both the biology of depression and anxiety. The aim of this study was to examine the platelet intracellular calcium response to serotonin and thrombin using spectrofluorometry in 14 patients with DSM-4 panic disorder compared to 14 matched controls. Patients did not show significantly higher baseline platelet intracellular calcium levels and serotonin stimulated levels of intracellular calcium than control subjects. There was a much smaller standard deviation in the control subjects than in the panic patients. The intracellular calcium response to thrombin activation was however greater in panic patients than in control subjects (P<0.001). The failure of this study to find enhanced sensitivity of 5-HT2 receptors in panic disorder is compatible with the findings of previous challenge studies that found no consistent dysregulation of serotonin in panic disorder. The enhanced thrombin sensitivity, nevertheless suggests some receptor mediated second messenger changes independent of serotonin in the disorder.

Tohen M, Frank E, Bowden CL, Colom F, Ghaemi SN, Yatham LN, Malhi GS, Calabrese JR, Nolen WA, Vieta E, Kapczinski F, Goodwin GM, Suppes T, Sachs GS, Chengappa KR, Grunze H, Mitchell PB, Kanba S, Berk M. · Department of Psychiatry, Division of Mood and Anxiety Disorders, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7792, San Antonio, TX 78229, USA. · Bipolar Disord. · Pubmed #19624385 No free full text.

Abstract: OBJECTIVES: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS: Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS: Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION: Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

Kapczinski F, Dias VV, Kauer-Sant'Anna M, Frey BN, Grassi-Oliveira R, Colom F, Berk M. · Bipolar Disorders Program, Laboratory of Molecular Psychiatry and INCT Translational Medicine, Hospital de Clinicas de Porto Alegre, Avenida Ramiro Barcelos 2350, 90035-903 PortoAlegre RS, Brazil. · Expert Rev Neurother. · Pubmed #19589046 No free full text.

Abstract: A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: individuals who present mood and anxiety symptoms and increased risk for developing threshold BD; Stage I--patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes; Stage II--patients who present rapid cycling or current axis I or II comorbidities; Stage III--patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers; and Stage IV--patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.

Hallam KT, Smith DI, Berk M. · Division of Psychology, RMIT University, Victoria, Australia. · J Affect Disord. · Pubmed #18501434 No free full text.

Abstract: While ECT is widely used for the management of severe and refractory depression, its utility in bipolar disorder is not extensively studied. The aim of this study was to examine the reported effectiveness of ECT in patients with unipolar and bipolar depression as reported by psychiatrists, nurses and patients (i.e. using objective and subjective measures). The records of 787 consecutive inpatient admissions to the Geelong Clinic, a private psychiatric centre based outside Melbourne, Victoria were reviewed in this file audit. Routine assessment measures were completed at admission and discharge, and included patient rated measures (Medical Outcomes Short Form SF-14 and Depression Anxiety and Stress Scale, DASS), nurse rated measures, (The Health of the Nation Outcome Scale, HoNOS) and a psychiatrist rated measure, the Clinical Global impression scale (CGI). In contrast to individuals with unipolar depression, where improvement was seen on all measures, in bipolar disorder, while improvement in clinician rated measures was seen (CGI, HoNOS), there was an absence of improvement in subjective measures of mood (DASS, SF14). This study suggests that in bipolar disorder, there is a poorer subjective response to ECT than in unipolar disorder.

Stafford L, Berk M, Jackson HJ. · Department of Psychology, School of Behavioural Science, University of Melbourne, Victoria 3010, Australia. · Gen Hosp Psychiatry. · Pubmed #17888808 No free full text.

Abstract: OBJECTIVE: Depression is common but frequently undetected in patients with coronary artery disease (CAD). Self-report screening instruments for assessing depression such as the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9 (PHQ-9) are available but their validity is typically determined in depressed patients without comorbid somatic illness. We investigated the validity of these instruments relative to a referent diagnostic standard in recently hospitalized patients with CAD. METHOD: Three months post-discharge for a cardiac admission, 193 CAD patients completed the HADS and PHQ-9. The Mini International Neuropsychiatric Interview (MINI) was the criterion standard. Scale reliability was calculated using Cronbach's alpha. Convergent validity was computed using Pearson's intercorrelations. Sensitivity and specificity for various cut-off scores for both measures and for the PHQ-9 categorical algorithm were calculated using receiver operating characteristics (ROC). For analyses, participants were assigned to two groups, 'major depressive disorder' or 'any depressive disorder'. RESULTS: For all calculations, alpha was 0.05 and tests were two-tailed. Internal consistencies for the two measures were excellent. Criterion validity for the PHQ-9 and HADS was good. We found no statistical differences between the PHQ-9 and HADS for detecting either group; however, the categorical algorithm of the PHQ-9 for diagnosing major depression had a superior LR+ when compared with the summed HADS or PHQ-9. The operating characteristics of the screening instruments for 'any depressive disorder' were slightly lower than for 'major depressive disorder'. Some optimum cut-off scores were lower than the generally recommended cut-off scores, particularly when screening for major depression (e.g., > or = 5/6 vs. > or = 10 and > or = 8 for PHQ-9 and HADS, respectively). Lowering the cut off scores substantially improved the sensitivity of these instruments while retaining specificity, thereby improving their usefulness to screen for CAD patients with depression. CONCLUSIONS: Both instruments have acceptable properties for detecting depression in recently hospitalized cardiac patients, and neither scale is statistically superior when summed scores are used. The categorical algorithm of the PHQ-9 for diagnosing major depression has a superior LR+ compared to the summed PHQ-9 and HADS scores. Use of the generally recommended cut-off scores should be cautious. In light of the aversive outcomes associated with depression in CAD, screening for depression is a clinical priority.

Ng F, Dodd S, Jacka FN, Leslie E, Berk M. · Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, Victoria, Australia. · Health Promot J Austr. · Pubmed #17501709 No free full text.

Abstract: ISSUE ADDRESSED: To assess the effectiveness of a walking program in a psychiatric in-patient unit. METHOD: In-patients at a private psychiatric unit were offered the opportunity to participate in a daily morning 40- minute walk led by an activity supervisor. After discharge, outcomes for patients who had regularly participated in the walking group (n=35) and patients who had not participated (n=49) were compared for length of stay during their period of admission and Clinical Global Impression-Severity (CGI-S) and Depression Anxiety Stress Scales (DASS) scores measured at admission and discharge. This was a retrospective analysis of data collected routinely. RESULTS: There were no significant differences between the two cohorts on most primary outcome measures, including length of stay, DASS scores at admission and at discharge and CGI-S scores at admission. Patients who had not participated in the walking group had a significantly lower score on a single measure, the CGI-S, than patients who had participated (p=0.001). CONCLUSIONS: This study showed no evidence that in-patients benefited from participating in the physical activity program. However, this must be interpreted within the confines of a number of study limitations and, as such, the findings can neither support nor refute the effectiveness of physical activities.

Conus P, Cotton S, Abdel-Baki A, Lambert M, Berk M, McGorry PD. · Département Universitaire de Psychiatrie CHUV, Université de Lausanne, Prilly, Switzerland. · Bipolar Disord. · Pubmed #16696823 No free full text.

Abstract: OBJECTIVE: Recent studies have shown that outcome in mania is worse than previously thought. Such studies have been conducted in selected samples with restrictive measures of outcome. We aimed to explore outcome and its predictors in a catchment area sample of first-episode psychotic mania of DSM-III-R bipolar I disorder. METHODS: Prospective 6 and 12 months follow-up was conducted with 87 DSM-III-R first-episode psychotic mania patients admitted to Early Psychosis Prevention and Intervention Centre between 1989 and 1997. Syndromic and symptomatic outcome were determined with the Brief Psychiatric Rating Scale; functional outcome with the Quality of Life Scale and Premorbid Adjustment Scale subitems. RESULTS: Symptomatic outcome was assessed in 67 patients at 6 months and 61 patients at 12 months, and functional outcome in 56 patients at 6 months and 49 patients at 12 months. Logistic regressions were conducted on 46 and 43 patients, respectively, to explore predictors of outcome. While 90% of patients achieved syndromic recovery at 6 and 12 months, 40% had not recovered symptomatically at 6 and 12 months, still presenting with anxiety or depression. A total of 66% of patients at 6 months and 61% of patients at 12 months failed to return to previous level of functioning. Age at intake, family history of affective disorder, illicit drug use and functional recovery at 6 months predicted functional outcome at 12 months. CONCLUSIONS: This study confirms poor symptomatic and functional outcome after first-episode psychotic mania. It suggests possible usefulness of early intervention strategies in bipolar disorders and need for developing specific interventions addressing anxiety, depression and substance abuse comorbidity.

Lewis R, Musella E, Berk M, Dodd S, McKenzie H, Hyland M. · Clinical and Biomedical Sciences, University of Melbourne, Community and Mental Health, Barwon Health, Swanston Centre, Geelong, Victoria, Australia. · J Eval Clin Pract. · Pubmed #15482418 No free full text.

Abstract: OBJECTIVE: To evaluate outcome and client and referrer satisfaction with the service provided by a Mood and Anxiety Disorders Unit (MADU). METHOD: MADU was a specialized clinical service for the assessment and management of individuals suffering with affective and anxiety disorders. Clients were referred to MADU from a variety of health service providers. A telephone survey of 30 clients and 20 referrers who have used the services of MADU was conducted, investigating outcome satisfaction with the service provided by MADU. RESULTS: Clients and referrers reported a high level of satisfaction with the service provided by MADU. There was a high degree of adherence to treatment recommendations. The mean Patient Global Impression of Improvement (PGI) rating by the clients before the MADU assessment was 2.74 (SD=1.27). In comparison the mean PGI rat-ing at the time of follow-up was 6.64 (SD=1.91). CONCLUSIONS: Specialist mood disorders units are a useful and potentially cost-effective additional service included as a part of a mental health service.

Seedat S, Stein DJ, Berk M, Wilson Z. · Department of Psychiatry, University of California San Diego, La Jolla 92037, USA. · Soc Psychiatry Psychiatr Epidemiol. · Pubmed #12242627 No free full text.

Abstract: BACKGROUND: As part of an international survey of mental health advocacy groups, information pertinent to patients' concerns regarding their diagnosis and treatment was gathered from South African members of a depression and anxiety support group (n = 404). METHODS: Questionnaires developed by GAMIAN, an international consortium of advocacy groups, were mailed along with explanatory letters and self-addressed envelopes to South African members and members in nine other countries, for completion. Of 1,000 questionnaires mailed in South Africa, 40.4 % were returned. RESULTS: The sample comprised patient members with anxiety-only (39 %), depression-only (8 %), mixed anxiety-depression (26 %), and other diagnoses (27 %). While one-third of respondents reported onset of symptoms before the age of 20, most waited 3-5 years before seeking help. After making contact with the health system, respondents experienced further delays in obtaining a correct diagnosis. In many instances, respondents were poorly informed of diagnosis and treatment (25 %), and nearly half of all respondents discontinued treatment on account of side-effects. CONCLUSIONS: Attempts to improve awareness of mental illness, and better communication between physicians and their patients, might help to break down some of the barriers patients encounter when seeking help.

Stein DJ, Wessels C, Zungu-Dirwayi N, Berk M, Wilson Z. · No affiliation provided · Depress Anxiety. · Pubmed #11301921 No free full text.

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