Depression: Malhi GS

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.

Malhi GS, Goodwin GM. · No affiliation provided · Aust N Z J Psychiatry. · Pubmed #17828650 No free full text.

This publication has no abstract.

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.

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.

Mitchell PB, Malhi GS. · School of Psychiatry, University of New South Wales, Black Dog Institute, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia. · Expert Opin Emerg Drugs. · Pubmed #17064222 No free full text.

Abstract: Bipolar disorder is a relatively common condition characterised by recurrent episodes of mania and depression, and associated with high levels of morbidity and mortality. Although there have been substantial advances in the pharmacotherapeutics of this condition over the last 10-15 years, the benefits have been predominantly in terms of tolerability and safety, with no new treatments being demonstrated to be more effective than lithium--the prototype mood stabiliser. This article reviews current and emerging medications for bipolar disorder. Most of the emerging treatments in pharmaceutical industry developmental programmes are new or modified anticonvulsants or atypical antipsychotics. A number of possible future directions and challenges for the field are discussed. The treatment of bipolar disorder is unlikely to advance substantially until the causative pathogenetic molecular processes are elucidated.

Lagopoulos J, Malhi GS, Ivanovski B, Cahill CM, Morris JG. · School of Psychiatry, The University of New South Wales, Australia. · Expert Rev Neurother. · Pubmed #16274337 No free full text.

Abstract: Depression is one of the most frequent comorbidities occurring in Parkinson's disease, affecting up to 50% of patients. Depression is associated with severe negative symptoms and has been shown to contribute to an increased rate of decline of both cognitive and motor function, profoundly impacting on the patient's quality of life. The symptoms of depression overlap with the motor features of Parkinson's disease, making detection difficult. Moreover, the lack of specialized screening tools means that depression remains undiagnosed and untreated in a high percentage of patients. However, depression in Parkinson's disease, when identified early, can be effectively treated with a variety of antidepressant medications, improving quality of life and preserving daily function. The focus of this review is to provide an overview of current knowledge regarding depression in Parkinson's disease, followed by a practical discussion addressing the issues of the detection, diagnosis and treatment.

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.

Olley A, Malhi GS, Mitchell PB, Batchelor J, Lagopoulos J, Austin MP. · School of Psychiatry, University of New South Wales and Mood Disorders Unit, Black Dog Institute, Prince of Wales Hospital, Sydney, Australia. · J Nerv Ment Dis. · Pubmed #15870616 No free full text.

Abstract: Bipolar disorder (BD) is a debilitating psychiatric illness that is uniquely characterized by switching between psychopathologically contrasting phases of mania and depression, often with intervening periods of euthymia. However, these periods of apparent clinical recovery (euthymia) are marked by subtle social, occupational, and cognitive impairments, profiled by recent neuropsychological investigations. Determining the cognitive changes across these three phases may help differentiate the disruptions that are mood state-dependent from those associated with underlying pathology. This article therefore critically reviews the reported neuropsychological impairments in BD and the methodological limitations facing such research. Integration of the available evidence, principally from the field of neuropsychology, when synthesized, implicates the prefrontal cortex in the etiopathogenesis of BD and posits cortical-subcortical-limbic disruption in recovered euthymic patients that manifests as cognitive dysfunction.

Mitchell PB, Malhi GS. · University of New South Wales, School of Psychiatry, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia. · Expert Rev Neurother. · Pubmed #15853476 No free full text.

Abstract: Recent studies have highlighted significant limitations in our capacity to effectively treat bipolar depression. This article reviews the present status of treatments for this condition, highlighting emerging new pharmacotherapies such as lamotrigine, olanzapine and quetiapine, while also addressing modern psychologic interventions such as cognitive behavioral therapy and psychoeducation. The role of older treatments such as lithium and the antidepressants is also discussed, particularly as a recent meta-analysis has thrown into question current heightened concern over antidepressant-induced mania. The advent of new pharmacologic and psychologic treatments provides optimism for improved outcomes for this highly disabling condition.

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.

Malhi GS, Ivanovski B, Szekeres V, Olley A. · Black Dog Institute, Prince of Wales Hospital, Sydney, Australia. · Can J Psychiatry. · Pubmed #15679204 No free full text.

Abstract: OBJECTIVE: To compare and contrast the neuropsychological profile of the 3 phases of bipolar disorder (BD) to achieve a better definition of BD and to identify potential state and trait deficits. METHODS: We conducted a search for English-language papers published in journals from 1965 onward, using the following terms in Medline and Embase: neuropsychology or neuropsychological and BD, depression, mania, and euthymia. We scrutinized suitable subheadings and retrieved familiar papers and literature. RESULTS: We initially identified more than 100 articles and then excluded reviews and papers that did not directly administer neuropsychological tests. This left 27 papers, which we further examined and the findings of which we tabulated and discussed. Cognitive and executive functioning deficits were found, including set-shifting, verbal fluency, planning, attention, and memory. CONCLUSIONS: The neuropsychological deficits found in bipolar depression, mania or hypomania, and euthymia provide important insights into the pathophysiology of BD and may, in future studies, form the basis of clinically meaningful subtypes.

Malhi GS, Parker GB, Greenwood J. · School of Psychiatry, University of New South Wales, Australia. · Acta Psychiatr Scand. · Pubmed #15667428 No free full text.

Abstract: OBJECTIVE: To present a functional model of depression facilitating research and clinical understanding. METHOD: The authors conducted a systematic literature search and reviewed articles pertaining to the neurochemistry and pathophysiology of depressive disorders, focusing on the contribution made by the principal monoamines to three differing depressive structural sub-types (i.e. psychotic, melancholic and non-melancholic). RESULTS: We suggest that the three structural depressive subtypes appear functionally underpinned by differential contributions of serotonergic, noradrenergic and dopaminergic neurotransmitters, so influencing phenotypic distinction (our structural model) and allowing an aetiological model to be derived with treatment specificity implications. CONCLUSION: The functional model logically iterates with the structural model of depression and provides a useful framework for conceptualizing the depressive disorders. This model provides a logic for distinguishing between principal depressive subtypes, pursuing their functional underpinnings and explaining treatment differential effects across the three sub-types.

Mitchell PB, Malhi GS. · School of Psychiatry, University of New South Wales and Mood Disorders Unit, Black Dog Institute, Prince of Wales Hospital, Sydney, NSW, Australia. · Bipolar Disord. · Pubmed #15541069 No free full text.

Abstract: OBJECTIVES: There has been increasing interest in the depressed phase of bipolar disorder (bipolar depression). This paper aims to review the clinical characteristics of bipolar depression, focusing upon its prevalence and phenomenology, related neuropsychological dysfunction, suicidal behaviour, disability and treatment responsiveness. METHODS: Studies on the prevalence of depression in bipolar disorder, the comparative phenomenology of bipolar and unipolar depression, as well as neuropsychology and brain imaging studies, are reviewed. To identify relevant papers, a literature search using MEDLINE and PubMed was undertaken. RESULTS: Depression is the predominant mood disturbance in bipolar disorder, and most frequently presents as subsyndromal, minor or dysthymic depression. Compared with major depressive disorder (unipolar depression), bipolar depression is more likely to manifest with psychosis, melancholic symptoms, psychomotor retardation (in bipolar I disorder) and 'atypical' symptoms. The few neuropsychological studies undertaken indicate greater impairment in bipolar depression. Suicide rates are high in bipolar disorder, with suicidal ideation, suicide attempts and completed suicides all occurring predominantly in the depressed phase of this condition. Furthermore, the depressed phase (even subsyndromal) appears to be the major contributant to the disability related to this condition. CONCLUSIONS: The significance of the depressed phase of bipolar disorder has been markedly underestimated. Bipolar depression accounts for most of the morbidity and mortality due to this illness. Current treatments have significant limitations.

Malhi GS, Lagopoulos J, Owen AM, Yatham LN. · School of Psychiatry, The University of New South Wales, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #15330938 No free full text.

Abstract: OBJECTIVE: To evaluate the literature pertaining to the use of functional magnetic resonance imaging (fMRI) in bipolar disorder research. METHOD: A search for papers published in English in journals from 1984 onwards was conducted using MedLine and EMBASE with the following terms: functional neuroimaging or fMRI and depression or bipolar disorder. In addition, retrieved papers and literature known to the authors was also scrutinized for further relevant reports. RESULTS: The research findings from 26 articles are tabulated and the results from 10 articles dealing specifically with bipolar disorder are discussed in detail. CONCLUSION: fMRI is a useful tool for investigating bipolar disorder. Preliminary studies point to trait and state abnormalities involving structures known to be associated with the generation and modulation of emotion. The patterns of fMRI activation are different to those found in healthy subjects and patients with major depression. FMRI studies are likely to provide valuable insights into the pathophysiology of bipolar disorder.

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.

Mitchell PB, Malhi GS, Ball JR. · School of Psychiatry, University of New South Wales, Prince of Wales Hospital, Randwick, NSW 2031, Australia. · Med J Aust. · Pubmed #15310256 links to  free full text

Abstract: There have been major advances in clinical understanding and treatment of bipolar disorder over the past decade. Randomised controlled trials of pharmacological treatments and psychological interventions have shown that there are effective short-term and long-term treatments for the disorder. Despite advances in treatment, diagnosis is often delayed or mistaken, and many people who could benefit are not using the treatments available. Functional and symptomatic recovery from episodes of bipolar disorder is frequently less complete than previously considered, and disability is often profound. Although manic episodes are the distinguishing feature of bipolar disorder, it appears that depression is the predominant mood disturbance and that much of the functional impairment associated with bipolar disorder results from this. Comorbidity with anxiety disorders or substance misuse is common. Advances in genetics, brain imaging and basic pharmacology are starting to provide understanding of the complex causative processes.

Malhi GS, Mitchell PB, Salim S. · School of Psychiatry, University of New South Wales, Randwick, Sydney, New South Wales, Australia. · CNS Drugs. · Pubmed #12467490 No free full text.

Abstract: Bipolar depression is the predominant abnormal mood state in bipolar disorder. However, despite the key pertinence of this phase of the condition, the focus of research and indeed of clinical interest in the management of bipolar disorder has been mainly on mania. Bipolar depression has been largely neglected, and early studies often failed to distinguish depression due to major unipolar depression from that due to bipolar disorder. Consequently, many treatments used in the management of major depression have been adopted for use in bipolar depression without any robust evidence of efficacy. The selective serotonin reuptake inhibitors (SSRIs), bupropion, tricyclic antidepressants and monoamine oxidase inhibitors are all effective antidepressants in the management of bipolar depression. They are all associated with a small risk of antidepressant-induced mood instability. The mood stabilisers lithium, carbamazepine and valproate semisodium (divalproex sodium) all appear to have modest acute antidepressant properties. Among these, lithium is supported by the strongest data, but the use of lithium in the treatment of bipolar depression as a monotherapeutic agent is limited by its slow onset of action. Recently, there has been a growing body of evidence suggesting that lamotrigine may have particular effectiveness in both the acute and prophylactic management of bipolar depression. Clinical management of bipolar depression involves various combinations of antidepressants and mood stabilisers and is partly determined by the context in which the depressive episode occurs. In general, 'de novo' and 'breakthrough' (where the patient is already receiving medication) bipolar depression may be successfully managed by initiating mood stabiliser monotherapy, to which an antidepressant or second mood stabiliser may be added at a later date, if necessary. Breakthrough episodes of bipolar depression occurring in patients receiving combination therapy (two mood stabilisers or a mood stabiliser plus an antidepressant) require either switching of ongoing medications or further augmentation. If this fails, then novel strategies or ECT should be considered. Bipolar depression is a disabling illness and the predominant mood state for the vast majority of those with bipolar disorder. It therefore warrants prompt management once suitably diagnosed, especially as it is associated with a considerable risk of suicide and in the majority of instances is eminently treatable.

Malhi GS, Sachdev P. · School of Psychiatry, University of New South Wales, Sydney, Australia. · J Psychosom Res. · Pubmed #12169345 No free full text.

Abstract: OBJECTIVE: To briefly describe the novel non-drug physical interventions currently in use in the investigation and treatment of neuropsychiatric disorders regarding their efficacy and potential future applications. METHODS: A systematic review of the literature concerning transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), vagus nerve stimulation (VNS) and neurosurgery for mental disorders (NMD) was conducted using Medline and literature known to the authors. RESULTS: A summary of each procedure is provided giving a succinct overview of efficacy, current applications and possible future indications. CONCLUSION: Novel and innovative physical interventions are currently being used to study brain function in health and disease. In particular, TMS has quickly established itself as a useful investigational tool and is emerging as a possible antidepressant therapy. Similarly, VNS has been applied successfully in the management of intractable epilepsy and is undergoing evaluation in the management of patients with treatment-resistant depression. DBS has shown significant promise in the treatment of Parkinson's disease and may have use in the management of obsessive-compulsive disorder. Finally, neurosurgical procedures for the treatment of mental disorders have been sufficiently refined to stage a comeback, although rigorous scientific study of their efficacy and indications is still necessary.

Mitchell PB, Malhi GS. · School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia. · Annu Rev Med. · Pubmed #11818469 No free full text.

Abstract: Over the past decade, the number of treatments available for bipolar disorder has undergone an extraordinary expansion. In that period, valproate and olanzapine have received regulatory approval in the United States for the acute treatment of mania, and carbamazepine has been indicated for this condition in many other countries. In addition to those agents, a number of other anticonvulsants (in particular lamotrigine, gabapentin, and topiramate) are in trials, as are the atypical antipsychotics clozapine and risperidone, and other novel compounds. This article critically reviews the evidence from controlled trials of these proposed "mood stabilizers," highlighting the strengths and limitations of the data for each compound. A major challenge to the field is the capacity to prove the prophylactic properties of agents for which effectiveness in acute mania and/or bipolar depression has been demonstrated. Finally, as the mechanisms of agents such as lithium are now becoming apparent, and the possibility of understanding the molecular defects underpinning the condition is no longer highly fanciful, the prospect of targeted therapies is considered feasible by both academia and the pharmaceutical industry.

Malhi GS, Bartlett JR. · Mood Disorders Unit, University Department of Psychiatry, Prince of Wales Hospital, High Street, Randwick, Sydney, NSW 2031, Australia. · Br J Neurosurg. · Pubmed #11198762 No free full text.

Abstract: After providing an overview of depression this article briefly reviews the development of psychosurgery and outlines the current procedures in use world wide. Stereotactic subcaudate tractotomy (SST) is described in particular detail, and the rationale for its use in the treatment of resistant depression is then discussed by considering the findings of neuropsychological, neurophysiological and neuroimaging studies. The emerging evidence suggests that the prefrontal cortex subserves an essential function in emotion and that disruption of its connections modifies mood.

Malhi GS, Moore J, McGuffin P. · SGDP Research Centre, Institute of Psychiatry, DeCrespigny Park, Denmark Hill, London SE5 8AF, UK. · Curr Psychiatry Rep. · Pubmed #11122950 No free full text.

Abstract: There is consistent evidence that major depression is familial and population-based twin studies as well as hospital register-based twin studies find substantial heritability. However, there is also a large proportion of variation in liability left to be explained by nongenetic factors. Although there seems little doubt that life events play a role in precipitating depression, studies that have attempted to examine familial liability along with social adversity find that environmental measures tend to be contaminated by genetic effects. Thus, the tendency to experience (or report) life events appears to be influenced by shared family environment, and for certain types of events there is a genetic component. The molecular genetic basis of liability to depression is an under-researched area, but some candidate gene studies show potentially promising results. Systematic mapping studies aiming to cover the entire genome are currently being launched.

Loo CK, Sachdev PS, Haindl W, Wen W, Mitchell PB, Croker VM, Malhi GS. · School of Psychiatry, University of New South Wales, Australia. · Psychol Med. · Pubmed #12946084 No free full text.

Abstract: BACKGROUND: High and low frequency repetititve transcranial magnetic stimulation (rTMS) are both effective in treating depression but have contrary effects on motor cortical activity. This study aimed to understand further the mechanisms of action of high and low frequency rTMS by examining their acute effects on regional cerebral blood flow (rCBF) in depressed patients. METHOD: Eighteen depressed subjects underwent brain single photon emission computerized tomography (SPECT) scanning using split-dose 99mTc-HMPAO, and were examined during sham and active rTMS to the left prefrontal cortex, at 15 Hz or 1 Hz (N=9 each). Relative rCBF changes were examined by statistical parametric mapping and by regions of interest analysis. RESULTS: High (15 Hz) frequency rTMS resulted in relative rCBF increases in the inferior frontal cortices, right dorsomedial frontal cortex, posterior cingulate and parahippocampus. Decreases occurred in the right orbital cortex and subcallosal gyrus, and left uncus. Low (1 Hz) frequency rTMS led to increased relative rCBF in the right anterior cingulate, bilateral parietal cortices and insula and left cerebellum. High frequency rTMS led to an overall increase, whereas low frequency rTMS produced a slight decrease, in the mean relative rCBF in the left dorsolateral prefrontal cortex. CONCLUSIONS: High (15 Hz) and low (1 Hz) frequency rTMS led to different frontal and remote relative rCBF changes, which suggests different neurophysiological and possibly neuropsychiatric consequences of a change in frequency of rTMS.

Loo CK, Mitchell PB, Croker VM, Malhi GS, Wen W, Gandevia SC, Sachdev PS. · Department of Psychiatry, Mood Disorders Unit, Black Dog Institute and Neuropsychiatric Institute, Prince of Wales Hospital, School of Psychiatry, University of New South Wales, Randwick, Australia. · Psychol Med. · Pubmed #12537034 No free full text.

Abstract: BACKGROUND: The efficacy and safety of bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, placebo-controlled study. METHOD: Nineteen medication-resistant depressed subjects were randomly assigned to 3 weeks of active or sham rTMS. Effects on mood and neuropsychological function were assessed. RESULTS: Both groups improved significantly in mood over the 3 weeks, but there was no significant difference between active and sham treatments. There were no significant neuropsychological effects. CONCLUSIONS: Bilateral rTMS was not superior to sham in treating resistant depression in this pilot study, but caused no neuropsychological impairment.

Sachdev PS, McBride R, Loo CK, Mitchell PB, Malhi GS, Croker VM. · School of Psychiatry, University of New South Wales, Sydney, Australia. · J Clin Psychiatry. · Pubmed #11780880 No free full text.

Abstract: BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.

Malhi GS. · Discipline of Psychological Medicine, University of Sydney, Sydney, Australia. · Bipolar Disord. · Pubmed #19594513 No free full text.

This publication has no abstract.