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In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for non-commercial entities to fill this gap. As a result, the evaluation of generic ketamine was delayed, piecemeal, uncoordinated, and insufficient to gain approval. Meanwhile, substantial commercial investment enabled the widespread registration of a patented, intranasal s-enantiomeric ketamine formulation (Spravato®) for depression. However, Spravato is priced at $600-$900/dose compared to ~$5/dose for generic ketamine, and the ~AUD$100 million annual government investment requested in Australia (to cover drug costs alone) has been rejected twice, leaving this treatment largely inaccessible for Australian patients 2 years after Therapeutic Goods Administration approval. Moreover, emerging evidence indicates that generic racemic ketamine is at least as effective as Spravato, but no comparative trials were required for regulatory approval and have not been conducted. Without action, this story will repeat regularly in the next decade with a new wave of psychedelic-assisted psychotherapy treatments, for which the original off-patent molecules could be available at low-cost and reduce the overall cost of treatment. Several systemic reforms are required to ensure that affordable, effective options become accessible; these include commercial incentives, public and public-private funding schemes, reduced regulatory barriers and more coordinated international public funding schemes to support translational research.
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Transtorno Depressivo Maior , Ketamina , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , AustráliaRESUMO
Symptoms of depression are common following traumatic brain injury (TBI), impacting survivors' ability to return to work, participate in leisure activities, and placing strain on relationships. Depression symptoms post TBI are often managed with pharmacotherapy, however, there is little research evidence to guide clinical practice. There have been a number of recent systematic reviews examining pharmacotherapy for post TBI depression. The aim of this umbrella review was to synthesize systematic reviews and meta-analyses of the effectiveness of pharmacotherapy for the management of post TBI depression in adults. Eligible reviews examined any pharmacotherapy against any comparators, for the treatment of depression in adults who had sustained TBI. Seven databases were searched, with additional searching of online journals, Research Gate, Google Scholar and the TRIP Medical Database to identify published and unpublished systematic reviews and meta-analyses in English up to May 2020. A systematic review of primary studies available between March 2018 and May 2020 was also conducted. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. The results are presented as a narrative synthesis. Twenty-two systematic reviews were identified, of which ten reviews contained a meta-analysis. No new primary studies were identified in the systematic review. There was insufficient high quality and methodologically rigorous evidence to recommend prescribing any specific drug or drug class for post TBI depression. The findings do show, however, that depression post TBI is responsive to pharmacotherapy in at least some individuals. Recommendations for primary studies, systematic reviews and advice for prescribers is provided. Review Registration PROSPERO (CRD42020184915).
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Lesões Encefálicas Traumáticas , Depressão , Adulto , Humanos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Depressão/tratamento farmacológico , Depressão/etiologiaRESUMO
Comparing the recommendations of two recently published national clinical practice guidelines for depression, this editorial highlights the concordance of advice concerning the selection and sequencing of therapies. Lifestyle and psychological interventions feature prominently and there is broad agreement regarding medication choice and optimisation strategies. The guidelines are therefore a useful resource.
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Depressão , Estilo de Vida , Humanos , Depressão/tratamento farmacológicoRESUMO
OBJECTIVE: The aim of the study is to examine the efficacy of omega-3 fatty acid as an adjunct to ongoing pharmacological treatments in patients with residual symptoms of depression and anxiety. METHODS/PROCEDURES: This randomized, double-blind, placebo-controlled, cross-over trial was conducted at a single private practice site. Participants were drawn from patients attending the practice.Patients meeting criteria had a 4-week run-in period where they continued to receive their prescribed medications and omega-3 supplements. Depression and anxiety ratings were assessed at recruitment and completion of the run-in phase. Patients were randomized to receive an omega-3 supplement (Neurospark) or placebo once daily for 8 weeks then crossed over to the alternative treatment. At the end of the double-blind, cross-over phase, patients received the supplement and were assessed after a 4-week run-out phase.Depression and anxiety symptoms were assessed using the Hamilton scales. Efficacy of treatment was assessed using a linear mixed model analysis with time, order of treatment, diagnosis, and their interaction as factors. Depression and anxiety scales were analyzed as independent measures. RESULTS: The study enrolled 47 patients (mean [SD] age, 46.1 [11.2] years; [59.6%] male). Depression scores did not significantly change across assessments ( P > 0.1); there was no effect of order of treatment ( P > 0.1) or an interaction between time, order of treatment, and psychiatric diagnosis ( P > 0.1). Anxiety scores were similarly unchanged across treatment visits and order of treatment, and there was no interaction between time, order of treatment, and psychiatric diagnosis. CONCLUSIONS: Omega-3 fatty acid supplementation did not significantly alter residual symptoms in this group of patients.
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Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Método Duplo-Cego , Ácidos Graxos Ômega-3/uso terapêutico , Resultado do Tratamento , Estudos Cross-OverRESUMO
OBJECTIVES: To extend current published guidance regarding the management of major depression in clinical practice, by examining complex cases that reflect real-world patients, and to integrate evidence and experience into recommendations. METHODS: The authors who contributed to recently published clinical practice guidelines were invited to identify important gaps in extant guidance. Drawing on clinical experience and shared knowledge, they then generated four fictional case studies to illustrate the real-world complexities of managing mood disorders. The cases focussed specifically on issues that are not usually addressed in clinical practice guidelines. RESULTS: The four cases are discussed in detail and each case is summarised using a life chart and accompanying information. The four cases reflect important real-world challenges that clinicians face when managing mood disorders in day-to-day clinical practice. To partly standardise the presentation of each case and for ease of reference we provide a Time Line, History Box and Management Chart, along with a synopsis where relevant. Discussion and formulation of the cases illustrate how to manage the complexities of each case and provide one possible pathway to achieving functional recovery. CONCLUSION: These cases draw on the combined clinical experience of the authors and illustrate how to approach diagnostic decision-making when treating major depressive disorder and having to contend with complex presentations. The cases are designed to stimulate discussion and provide a real-world context for the formulation of mood disorders.
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Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Transtornos do Humor , Recuperação de Função FisiológicaRESUMO
OBJECTIVE: To review the usefulness of esketamine for treatment-resistant depression. METHOD: Pivotal trials of intranasal esketamine in treatment-resistant depression were synthesized as a narrative review. RESULTS: Esketamine is postulated to act through antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors, but opioidergic effects may also be involved. Unlike intravenous ketamine, esketamine is given intranasally (under clinical observation), usually in addition to an oral antidepressant. Trials compared esketamine plus antidepressant versus placebo plus antidepressant. At 4 weeks, remission was 37% higher with esketamine/antidepressant than placebo/antidepressant. Speed of response and improvement in suicidality were comparable. In stable remitters on esketamine/antidepressant, 45% relapsed when esketamine was withdrawn over the following 6 months (whereas 25% relapsed on esketamine/antidepressant). Response appears less likely in patients with multiple antidepressant failures. Adverse effects include dissociation, dizziness, nausea, sedation, and headache but no psychosis. Hypertension affected 13%, especially older patients. Dose frequency is twice-weekly for 4 weeks, then weekly/fortnightly thereafter. No abuse has been reported. Unsubsidised cost may be beyond the reach of many Australians. CONCLUSION: Intranasal esketamine plus antidepressant has been approved by regulators as moderately effective and acceptably tolerable for treatment-resistant depression. Cost is a drawback. Use often needs to be long-term and vigilance for abuse is essential.
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Transtorno Depressivo Resistente a Tratamento , Ketamina , Humanos , Antidepressivos/uso terapêutico , Austrália , Depressão , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêuticoRESUMO
OBJECTIVE: To compare the 2022 NICE guidelines (NG222) and 2020 RANZCP clinical practice guidelines (MDcpg2020) recommendations for the treatment of depression using psychodynamic psychotherapy. CONCLUSIONS: Both guidelines recommend psychological interventions first-line. However, only short-term psychodynamic psychotherapy (STPP) is recommended, and in the NG222 it is ranked last for less severe depression and 7th for more severe depression. In contrast, cognitive behavioural therapy and behavioural activation are deemed the more clinically effective and cost-effective psychological therapies. And antidepressants play a significant role - largely in more severe depression.
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Terapia Cognitivo-Comportamental , Transtorno Depressivo , Psicoterapia Breve , Psicoterapia Psicodinâmica , Humanos , Depressão/terapia , Transtorno Depressivo/terapia , Psicoterapia , Resultado do TratamentoRESUMO
With the exponential growth in investment attention to brain health-solutions spanning brain wellness to mental health to neurological disorders-tech giants, payers, and biotechnology companies have been making forays into this field to identify technology solutions and pharmaceutical amplifiers. So far, their investments have had mixed results. The concept of open innovation (OI) was first coined by Henry Chesbrough to describe the paradigm by which enterprises allow free flow of ideas, products, and services from the outside to the inside and vice versa in order to remain competitive, particularly in rapidly evolving fields where there is abundant, relevant knowledge outside the traditional walls of the enterprise. In this article, we advocate for further exploration and advancement of OI in brain health.
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OBJECTIVE: The Better Health Access Initiative added 32 Medicare Benefits Schedule (MBS) item numbers in 2006 to increase the number of people with access to mental health care. We investigated trends in the provision of outpatient Medicare-subsidised psychiatric services since the introduction of these item numbers in 2006 through 2019. METHODS: Medicare Benefits Schedule aggregated item-number claims data were obtained from the Services Australia Medicare website, between January 2006 and December 2019 inclusive, for face-to-face psychiatrist consultations. Item number rates were collated and graphed per 100,000 population according to year and item number. RESULTS: There has been an increase in the number of claims for new patient assessments (291-296) and a reduction in most ongoing care Medicare item numbers, especially longer appointments that are often associated with psychotherapy provision (306-308). CONCLUSION: There have been changes in private psychiatric practice in Australia over the past 14 years. There are several possible causes for these changes and further research is required to determine the impact on patient care.
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Pacientes Ambulatoriais , Psiquiatria , Idoso , Humanos , Programas Nacionais de Saúde , Prática Privada , Encaminhamento e ConsultaRESUMO
OBJECTIVE: To rebut the claims made in an opinion piece by Anaf and colleagues regarding the recommendations for psychotherapy within the 2020 RANZCP Mood Disorders Clinical Practice Guidelines (CPG). CONCLUSIONS: The CPG attaches importance to psychological interventions and recommends their administration as first-line in the treatment of depression. The concerns raised by Anaf and colleagues have no basis and are readily dismissed by referring to the guidelines. Therefore, we strongly encourage clinicians to formulate their own views by reading the guidelines for themselves.
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Psiquiatria , Sociedades Médicas , Austrália , Humanos , Transtornos do Humor/terapia , Nova ZelândiaRESUMO
Several studies have investigated the risk of dementia in posttraumatic stress disorder (PTSD) using a varying methodology. Epidemiological studies have found an increased risk of dementia with PTSD in Vietnam veterans as well as the general population. Laboratory studies reported the accelerated formation of ß-amyloid and tau, which represent the primary pathology of Alzheimer's dementia in animal models of PTSD. These investigations were conducted against a background of cognitive impairment and atrophy of the hippocampus and certain cortical areas in patients with PTSD. Very few studies have investigated the pathological basis in humans for the reported association of PTSD with dementia. This important gap in the literature has recently been partly addressed by very few studies that estimated the burden of ß-amyloid and tau. The PET studies did not show an association between PTSD and the specific pathology of Alzheimer's disease or signs of neurodegenerative diseases underlying other dementia syndromes. Another study demonstrated decreased plasma ß-amyloid load and increased plasma ß-amyloid 42/40 ratio in PTSD without PET evaluation. While PTSD is associated with an increased risk of dementia syndrome in general, there is no convincing evidence that it causes or accelerates the pathology of Alzheimer's disease, which causes the most common type of dementia. Factors that may account for the association between PTSD and a clinical diagnosis of dementia are discussed in this review.
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Doença de Alzheimer , Disfunção Cognitiva , Transtornos de Estresse Pós-Traumáticos , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides , Humanos , Tomografia por Emissão de Pósitrons , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Proteínas tauRESUMO
BACKGROUND: Certain nutrient supplements (nutraceuticals) may target neurobiological pathways perturbed in bipolar disorder (BD) such as inflammation, oxidative stress, and mitochondrial dysfunction. Nutraceuticals thus may have a potential role as adjunctive treatments for BD. METHODS: A search of Embase via embase.com, PubMed via PubMed, Cumulated index to nursing and allied health literature (CINAHL) Complete via EBSCO, and Cochrane Central Register of Controlled Clinical Trials via cochranelibrary.com was conducted to identify published randomized controlled trials assessing the efficacy of nutraceuticals on mood symptomatology in adults with BD. Search terms for BD, nutraceuticals, and clinical trials (total search terms = 75) were used to search from inception to February 20, 2020. The Cochrane Collaboration's tool for assessing the risk of bias in randomized trials was used to assess the risk of bias. RESULTS: A total of 1,712 studies were identified through the search. After rigorous screening, 22 studies were included in the review. There was large variability across the studies with 15 different nutraceutical agents assessed and as such insufficient homogeneity for a meta-analysis to be conducted (I2 > 50%). Studies revealed promising, albeit conflicting, evidence for omega-3 fatty acids and N-acetylcysteine. Isolated positive results were reported for coenzyme Q10. CONCLUSION: Given nutraceuticals are tolerable and accessible, they may be useful as potential adjunctive treatments for BD. Nutraceuticals targeting neuroinflammation or mitochondrial activity may have the most potential for the depressive phase. However, further studies are required to determine efficacy.
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Transtorno Bipolar , Suplementos Nutricionais , Adulto , Transtorno Bipolar/tratamento farmacológico , HumanosRESUMO
This article is a detailed response to the criticisms levelled by the authors of an accompanying viewpoint, which claims that the positioning of repetitive transcranial magnetic stimulation (rTMS) in the 2020 Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for the management mood disorders (MDcpg2020) is incorrect. We, the authors of the MDcpg2020, strongly refute these assertions and argue that first we have determined the positioning of rTMS using the same criteria as those applied to other treatments for depression. Second, in accordance with National Health and Medical Research Council (NHMRC) guidelines, the processes by which we have developed the MDcpg2020 have been guided by best practice and have been overseen throughout by the RANZCP. Third, our objective and detailed examination of the relevant research has shown that the evidence needed to support the positioning of rTMS alongside standard therapies for depression is severely deficient. And therefore, as a consequence, we set out clearly both our logic and reasoning with respect to interpreting rTMS data and outline our evidence-informed position in which rTMS remains a potential alternative therapy that can be considered in certain clinical circumstances once both suitable psychological and pharmacological treatments have been trialled. We also discuss why, until further research is conducted, rTMS is perhaps best regarded as an experimental therapy and an investigational tool, and to assist in this regard, we propose a framework for consideration by those conducting rTMS studies in the future. Thus, based on current knowledge, we conclude that rTMS does not have a sufficient evidence base to warrant recognition as a standard therapy for depression alongside established treatments such as psychological interventions, pharmacotherapy, and electroconvulsive therapy. Furthermore, there is no clinical profile for depressed patients that might benefit from rTMS and therefore tolerability alone is not good enough reason to promote rTMS in the management of major depression.
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Transtorno Depressivo Maior , Eletroconvulsoterapia , Austrália , Humanos , Transtornos do Humor , Estimulação Magnética TranscranianaRESUMO
OBJECTIVES: To provide advice and guidance regarding the management of mood disorders, derived from scientific evidence and supplemented by expert clinical consensus to formulate s that maximise clinical utility. METHODS: Articles and information sourced from search engines including PubMed, EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (e.g. books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Relevant information was appraised and discussed in detail by members of the mood disorders committee, with a view to formulating and developing consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous consultation and external review involving: expert and clinical advisors, key stakeholders, professional bodies and specialist groups with interest in mood disorders. RESULTS: The Royal Australian and New Zealand College of Psychiatrists mood disorders clinical practice guidelines 2020 (MDcpg2020) provide up-to-date guidance regarding the management of mood disorders that is informed by evidence and clinical experience. The guideline is intended for clinical use by psychiatrists, psychologists, primary care physicians and others with an interest in mental health care. CONCLUSION: The MDcpg2020 builds on the previous 2015 guidelines and maintains its joint focus on both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. MOOD DISORDERS COMMITTEE: Gin S Malhi (Chair), Erica Bell, Darryl Bassett, Philip Boyce, Richard Bryant, Philip Hazell, Malcolm Hopwood, Bill Lyndon, Roger Mulder, Richard Porter, Ajeet B Singh and Greg Murray.
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Transtornos do Humor , Guias de Prática Clínica como Assunto , Psiquiatria , Austrália , Humanos , Transtornos do Humor/diagnóstico , Transtornos do Humor/terapia , Nova Zelândia , Sociedades MédicasRESUMO
Challenging behaviours are a common and distressing consequence of acquired brain injury (ABI). There are no evidence-based guidelines for managing challenging behaviours after ABI, leaving clinicians with few resources to guide practice. Findings from case studies and single-subject experimental designs support the use of positive behaviour support (PBS) interventions for challenging behaviour post-ABI. This paper introduces PBS + PLUS: a multi-component and flexible PBS intervention using a person-driven collaborative approach to build a meaningful life and self-regulate behaviour after ABI. PBS + PLUS is currently being examined in a randomized controlled trial (RCT). Three detailed pilot case studies illustrate the highly individualized implementation of the programme, delivered to the individuals with ABI and carers over 12 months by a transdisciplinary team including neuropsychologists, occupational therapists, and psychiatrists. Objective behavioural outcomes are reported for participants using the Overt Behaviour Scale at baseline and four-monthly intervals for two years. Goal attainment scaling was used to measure personally meaningful goals. The qualitative appraisals of the intervention by participants, families and carers, and 12-month follow-up outcomes are described. The advantages and challenges of programme delivery are discussed. These case studies will assist clinicians and service providers to implement PBS + PLUS in anticipation of the results of the RCT.
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Lesões Encefálicas , Terapia Comportamental , Lesões Encefálicas/complicações , Cuidadores , Humanos , Projetos Piloto , Projetos de PesquisaRESUMO
Pseudobulbar affect is a debilitating condition that significantly reduces quality of life for many individuals following traumatic brain injury (TBI). It is characterized by embarrassing and often uncontrollable episodes of crying or laughter. The aim of this systematic review was to evaluate the effectiveness of pharmacotherapy as compared to all other comparators for the management of pseudobulbar affect in adults who have sustained TBI. Six databases were searched, with additional hand searching of journals, clinical trials registries and international drug regulators to identify published and unpublished studies in English up to June 2018. Studies were eligible for this review if they included adults who had sustained a medically confirmed TBI and presented with pseudobulbar affect. All pharmacotherapy and comparator interventions were considered for inclusion, and study design was not limited to randomised controlled trials. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Two quasi-experimental studies examining the effectiveness of dextrometamorphan/quinidine (DM/Q) were identified. These studies reported that DM/Q was effective in reducing symptoms of pseudobulbar affect and had a positive safety profile, over follow-up periods of 3 months (n = 87) and 12 months (n = 23). However, both studies were limited by lack of a control group and a high dropout rate. The findings of twelve case reports examining the effectiveness of DM/Q (n = 6) and anti-depressants (n = 6) are also discussed. Further research is required to determine which pharmacological interventions provide the best outcomes for individuals with pseudobulbar affect following TBI, with consideration given to side effect profiles and financial costs.
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Sintomas Afetivos/tratamento farmacológico , Sintomas Afetivos/etiologia , Lesões Encefálicas Traumáticas/complicações , Dextrometorfano/farmacologia , Neurotransmissores/farmacologia , Quinidina/farmacologia , Dextrometorfano/efeitos adversos , Combinação de Medicamentos , Humanos , Neurotransmissores/efeitos adversos , Quinidina/efeitos adversosRESUMO
OBJECTIVES: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020 , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression. RESULTS: The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response. CONCLUSIONS: The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg2020 . The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/métodos , Transtornos do Humor/terapia , Guias de Prática Clínica como Assunto , Psiquiatria , Austrália , Consenso , Transtorno Depressivo Maior/diagnóstico , Humanos , Transtornos do Humor/diagnóstico , Nova Zelândia , Sociedades MédicasRESUMO
OBJECTIVES: To provide a succinct, clinically useful summary of the management of bipolar disorder, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020 , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on bipolar disorder. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of bipolar disorder. RESULTS: The bipolar disorder summary provides a systematic approach to diagnosis, and a logical clinical framework for management. It addresses the acute phases of bipolar disorder (mania, depression and mixed states) and its longer-term management (maintenance and prophylaxis). For each phase it begins with Actions, which include important strategies that should be implemented from the outset wherever possible. These include for example, lifestyle changes, psychoeducation and psychological interventions. In each phase, the summary advocates the use of Choice medications for pharmacotherapy, which are then used in combinations along with additional Alternatives to manage acute symptoms or maintain mood stability and provide prophylaxis. The summary also recommends the use of electroconvulsive therapy (ECT) for each of the acute phases but not for maintenance therapy. Finally, it briefly considers bipolar disorder in children and its overlap in adults with borderline personality disorder. CONCLUSIONS: The bipolar disorder summary provides up to date guidance regarding the management of bipolar disorder, as set out in the MDcpg2020 . The recommendations are informed by evidence and clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians but will be of interest to anyone involved in the management of patients with bipolar disorder.
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Antidepressivos/uso terapêutico , Transtorno Bipolar/terapia , Eletroconvulsoterapia/métodos , Transtornos do Humor/terapia , Guias de Prática Clínica como Assunto , Psiquiatria , Adulto , Austrália , Transtorno Bipolar/diagnóstico , Criança , Consenso , Humanos , Transtornos do Humor/diagnóstico , Nova Zelândia , Sociedades MédicasRESUMO
OBJECTIVES: Individuals with bipolar disorder (BD) generally engage in low levels of physical activity (PA), and yet few studies have investigated the relationship between PA and change in BD symptom severity. The aim of this subanalysis of an adjunctive nutraceutical randomized controlled trial for the treatment of bipolar depression was to explore the relationship between PA, the active adjunctive treatments (a nutraceutical "mitochondrial cocktail"), and clinical outcomes. METHODS: Participants with bipolar depression were randomized to receive N-acetylcysteine alone, N-acetylcysteine with a combination of nutraceuticals (chosen for the potential to increase mitochondrial activity), or placebo for 16 weeks. Participants (n = 145) who completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF; measured at Week 4) were included in this exploratory subanalysis. Assessments of BD symptoms, functioning, and quality of life were completed at monthly visits up until Week 20. Generalised Estimating Equations were used to explore whether IPAQ-SF scores were a moderator of treatment received on outcomes of the study. RESULTS: Week-4 PA was not related to changes in Montgomery Åsberg Depression Rating Scale scores across the study until Week 20. However, participants who engaged in more PA and who received the combination treatment were more likely to have a reduction in scores on the Bipolar Depression Rating Scale (P = 0.03). However, this was not consistent in all domains explored using the IPAQ-SF. Participants who engaged in higher levels of PA also experienced greater improvement in social and occupational functioning and less impairment in functioning due to their psychopathology and improvement in quality of life at Week 20, irrespective of treatment. CONCLUSIONS: This study provides novel evidence of the association between PA and reduction in BD symptoms in a nutraceutical clinical trial. However, further research assessing the potential synergistic effects of PA in BD is required.
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Transtorno Bipolar , Transtorno Bipolar/tratamento farmacológico , Suplementos Nutricionais , Método Duplo-Cego , Exercício Físico , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
AIMS: We aimed to explore the relationships between diet quality, dietary inflammatory potential or body mass index and outcomes of a clinical trial of nutraceutical treatment for bipolar depression. METHODS: This is a sub-study of a randomised controlled trial of participants with bipolar depression who provided dietary intake data (n = 133). Participants received 16 weeks adjunctive treatment of either placebo or N-acetylcysteine-alone or a combination of mitochondrial-enhancing nutraceuticals including N-acetylcysteine (combination treatment). Participants were followed up 4 weeks post-treatment discontinuation (Week 20). Diet was assessed by the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies, Version 2, converted into an Australian Recommended Food Score to measure diet quality, and energy-adjusted dietary inflammatory index score to measure inflammatory potential of diet. Body mass index was also measured. Generalised estimating equation models were used to assess whether diet quality, energy-adjusted dietary inflammatory index score and/or body mass index were predictors of response to significant outcomes of the primary trial: depression symptoms, clinician-rated improvement and functioning measures. RESULTS: In participants taking combination treatment compared to placebo, change in depression scores was not predicted by Australian Recommended Food Score, dietary inflammatory index or body mass index scores. However, participants with better diet quality (Australian Recommended Food Score) reported reduced general depression and bipolar depression symptoms (p = 0.01 and p = 0.03, respectively) and greater clinician-rated improvement (p = 0.02) irrespective of treatment and time. Participants who had a more anti-inflammatory dietary inflammatory index had less impairment in functioning (p = 0.01). Combination treatment may attenuate the adverse effects of pro-inflammatory diet (p = 0.03) on functioning. Participants with lower body mass index who received combination treatment (p = 0.02) or N-acetylcysteine (p = 0.02) showed greater clinician-rated improvement. CONCLUSION: These data support a possible association between diet (quality and inflammatory potential), body mass index and response to treatment for bipolar depression in the context of a nutraceutical trial. The results should be interpreted cautiously because of limitations, including numerous null findings, modest sample size and being secondary analyses.