Mood and anxiety disorders typically begin in adolescence and have overlapping clinical features but marked inter-individual variation in clinical presentation. The use of multimodal neuroimaging ...data may offer novel insights into the underlying brain mechanisms. We applied Heterogeneity Through Discriminative Analysis (HYDRA) to measures of regional brain morphometry, neurite density, and intracortical myelination to identify subtypes of youth, aged 9-10 years, with mood and anxiety disorders (N = 1931) compared to typically developing youth (N = 2823). We identified three subtypes that were robust to permutation testing and sample composition. Subtype 1 evidenced a pattern of imbalanced cortical-subcortical maturation compared to the typically developing group, with subcortical regions lagging behind prefrontal cortical thinning and myelination and greater cortical surface expansion globally. Subtype 2 displayed a pattern of delayed cortical maturation indicated by higher cortical thickness and lower cortical surface area expansion and myelination compared to the typically developing group. Subtype 3 showed evidence of atypical brain maturation involving globally lower cortical thickness and surface coupled with higher myelination and neural density. Subtype 1 had superior cognitive function in contrast to the other two subtypes that underperformed compared to the typically developing group. Higher levels of parental psychopathology, family conflict, and social adversity were common to all subtypes, with subtype 3 having the highest burden of adverse exposures. These analyses comprehensively characterize pre-adolescent mood and anxiety disorders, the biopsychosocial context in which they arise, and lay the foundation for the examination of the longitudinal evolution of the subtypes identified as the study sample transitions through adolescence.
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.
This double-blind placebo-controlled, fixed/flexible-dose phase 2 trial assessed the efficacy, safety, and tolerability of cariprazine vs. placebo for depressive episodes associated with bipolar I or ...II disorder. Primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (baseline to week 8), and secondary endpoint was mean Clinical Global Impressions-Improvement score (week 8). Patients were randomized (N = 233) 1:1:1 to placebo, 'low-dose' 0.25-0.5 mg/day or 'high-dose' 1.5-3.0 mg/day cariprazine. Adverse events, laboratory results, vital signs, extrapyramidal symptoms, and suicide risk were monitored. Neither cariprazine group significantly separated from placebo in primary (mixed-effect model repeated measures MADRS least-squares mean differences: low-dose = -0.7, P = 0.7408; high-dose = 0.0, P = 0.9961) or secondary efficacy measures. No new safety signals with cariprazine were observed and common treatment-emergent adverse events (≥5% of cariprazine patients and twice the rate of placebo) included insomnia, akathisia, dry mouth, nausea, weight increased, diarrhea, restlessness, vomiting, musculoskeletal stiffness, migraine, and cough. Metabolic and weight changes were generally similar for cariprazine and placebo. Factors that may have affected the outcome of the trial were identified, which helped to inform the design and conduct of subsequent phase 2b/3 clinical trials of cariprazine in bipolar depression.
Objectives
Although several studies have reported on predictors of employment in individuals with bipolar disorder (BD), the magnitude of the impact of these variables is unclear as no previous ...studies have estimated the collective effect sizes (ESs). The present meta‐analysis estimated ESs and explored which of these variables are associated with positive employment outcomes.
Methods
We searched for articles published between 2000 and 2011 that reported associations between sociodemographic, clinical, psychosocial, and/or cognitive variables with employment outcomes in BD. Of the 781 articles identified, 22 met the inclusion criteria and were included in the final analysis (n = 6,301). Weighted correlation coefficients (r‐index) were computed as ESs for each of the predictor variables, which were grouped into six categories: cognitive performance, symptomatology, sociodemographic factors, course of illness, clinical variables, and other personal factors. The overall ES (Rw) was estimated by assuming random‐effect models. Sensitivity analyses were also performed to determine the robustness of the findings.
Results
Significant predictors of favorable employment outcomes included: cognitive performance (e.g., verbal memory, Rw = 0.33; executive function, Rw = 0.26), sociodemographic factors (e.g., years of education, Rw = 0.23), course of illness (e.g., number of lifetime psychiatric hospitalizations, Rw = −0.35), symptomatology (e.g., depression, Rw = −0.25), and other personal factors (e.g., personality disorder, Rw = −0.49).
Conclusions
Overall, the cognitive performance and course of illness had larger average ESs than symptomatology or sociodemographic factors on favorable employment outcomes. These findings may help to guide the design of more effective work interventions for people with BD.
Depression is the most commonly experienced mood state over the life span in individuals with bipolar disorder (BD) and is the primary driver of functional impairment and suicidality in BD. Despite ...this, there are few effective treatments for BD depression, with only a handful of atypical anti-psychotics and inconsistent evidence for traditional mood stabilizing agents. There have been few major 'breakthroughs' in the treatment of BD depression, and until recently, few agents that work via novel mechanisms of action to exert therapeutic effects. Here, we review treatments for BD depression which are emergent or on the horizon. Included are new atypical anti-psychotics, glutamate modulators (ketamine and cycloserine/lurasidone), neurosteroid modulators (zuranolone), anti-inflammatories and mitochondrial modulators, cannabidiol (CBD) and psilocybin. New atypical anti-psychotics lumateperone and cariprazine have demonstrated efficacy in large-scale, placebo-controlled, double-blind randomized controlled trials (RCT) in treatment of BD depression. Non-racemic amisulpride showed potential therapeutic benefit in one RCT which requires replication. Three small RCTs examined the efficacy of intravenous ketamine in BD depression and showed rapid antidepressant and anti-suicidal effects after a single infusion. Anti-inflammatory and mitochondrial modulators show inconsistent evidence for efficacy. There are currently no adequately powered RCTs of zuranolone, psilocybin or CBD in BD depression to support their use. While there are potentially efficacious, mechanistically novel agents on the horizon, they require further study and validation. Further investigation on how these agents may impact specific subgroups of patients will also advance the field.
The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in ...2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
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