Rodrigo B. Mansur's research while affiliated with Toronto Western Hospital and other places

Publications (264)

Article
Introduction: Cognitive impairment is a core feature of bipolar disorder (BD) that impedes recovery by preventing the return to optimal socio-occupational functioning and reducing quality of life. Presently, there are no efficacious treatments for cognitive impairment in BD, but many pharmacological interventions are being considered as they have...
Preprint
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Background Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pedi...
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Borderline personality disorder (BPD) has high rates of comorbidity with mood disorders, including treatment-resistant depression (TRD). Comorbidity of BPD with depression is associated with poorer response to antidepressants. Intravenous ketamine is a novel treatment for TRD that has not been specifically evaluated in patients with comorbid BPD. I...
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Objectives: A low protein diet (LPD) for chronic kidney disease (CKD) is a core dietary therapy to slow CKD progression. A study showed depressive symptoms are more common in populations with an LPD. In this cross-sectional study, we evaluated depressive symptoms and health-related quality of life (HRQOL) in patients with CKD. Methods: A total o...
Article
Converging evidence has suggested that disturbances in monetary reward processing may subserve the shared biosignature between major depressive disorder (MDD) and obesity. However, there remains a paucity of studies that have evaluated the deficits in specific subcomponents of reward functioning in populations with MDD and obesity comorbidity. We e...
Article
Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ke...
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Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. “Metabolic jet lag” refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed throu...
Article
Previous studies have evaluated the relationship between anhedonia and suicidality; however, to our knowledge, there has been no quantitative synthesis evaluating the foregoing association to date. Herein, this meta-analysis aims to provide a quantitative synthesis of the extant literature reporting on the association between levels of anhedonia ac...
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Background Insulin resistance (IR) is a potential predictor of antidepressant treatment response. Aims We assess changes in IR after antidepressant treatment and whether these changes have any effect on treatment response. Also, to see whether changes in IR mediates relationship between C-reactive protein (CRP) and antidepressant efficacy. Method...
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Purpose of Review Cognitive dysfunction remains a major source of poor patient reported outcomes in mood disorders. Similarly, cognitive impairment is commonly reported in many metabolic disorders including type II diabetes mellitus (T2DM) and obesity. Current treatment options do not provide optimal specificity in targeting cognitive dysfunction,...
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Background: Cognitive dysfunction is an impairing core symptom of depression. Among adults with major depressive disorder (MDD) treated with antidepressants, residual cognitive symptoms interfere with patient-reported outcomes. The foregoing characterization of cognitive symptoms provides the rationale for screening and assessing the severity of c...
Article
Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia; however, a comprehensive review on NAFLD and psychiatric disorders remains to be delin...
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Background Depression is a disease that is commonly accompanied by elderly chronic kidney disease (CKD) patients, but when the two diseases are accompanied, etiology or combination are not well known. We aimed to evaluate the etiology of CKD and comorbid depression by investigating bone disorders that are observed in persons affected by both CKD an...
Preprint
Full-text available
Non-alcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia, however a comprehensive review on NAFLD and psychiatric disorders remains to be delin...
Article
Objective Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for...
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Objective Ketamine has demonstrated rapid and significant antidepressant effects in patients with treatment resistant depression (TRD). Herein, we conducted a systematic review to determine ketamine's efficacy as a function of the stage of treatment resistance (e.g., number of failed treatments) among individuals with TRD. Methods A systematic sea...
Article
Introduction Bipolar disorder (BD) is characterized by a pro-inflammatory biotype, and is a major cause of cardiovascular disease (CVD), consequently causing elevated rates of morbidity and mortality among individuals with BD. Methods The present study is based on a 12-week clinical trial assessing the antidepressant effects of adjunctive inflixim...
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Background: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. Objectives: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. Methods: We conducted a systematic search on January 24, 2022, in PubMed, Scopus,...
Article
Background Available studies have evaluated cognition in the unaffected relatives of bipolar disorder patients; however, to our knowledge, there has been no quantitative analysis evaluating the foregoing association. Herein, this meta-analysis aims to provide a quantitative synthesis of the extant literature reporting on the association between per...
Article
Replicated clinical trials have demonstrated rapid and robust antidepressant effects with ketamine in treatment resistant mood disorders. Sex (biological) and gender differences in therapeutic effects for any new intervention is an important consideration, however, the differential efficacy, safety and tolerability of ketamine in males versus femal...
Article
The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocy...
Article
Background A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021–2022. The aim of this review is to provide a scope of the candida...
Article
Objectives : The study herein aimed to assess the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), as well as general and abdominal obesity in patients with bipolar disorder (BD). We also compared the prevalence of T2DM and general obesity in patients with BD with age- and gender-matched healthy controls. Method : A s...
Article
Importance COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. Objective To quantify the proportion of individuals experiencing fatigue and cognitive imp...
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Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a natur...
Article
Background : Clinical practice guidelines (CPG) are an important tool for implementation of evidence-based clinical care. Despite clinical trials showing lack of efficacy of some agents in bipolar disorder (BD), they are still frequently prescribed in clinical practice. The objective of this study was to systematically review the CPG recommendation...
Article
Objective .To identify a meaningful change threshold (MCT) in depression outcomes in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD) receiving intravenous ketamine treatment at a community-based mood disorders center. Method .A triangular approach integrating both anchor-based and distributive methods was u...
Article
Approximately 0.35% to 1% of the general population is afflicted with psychotic depression at some time in their life. Psychotic depression is a subtype of major depressive disorder characterized by mood congruent hallucinations and/or delusions. Patients with psychotic depression often represent the most severe cases, with high relapse and mortali...
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Objective The objective of this research was to evaluate the impact of federal, public health and social support programs on national suicide rates in Canada. Design Cross-sectional study. Setting Canadian National Database (i.e., Statistics Canada) and Statista. Participants Population-level data, and economic and consumer market data. Main Ou...
Article
A proportion of individuals with major depressive disorder (MDD) do not receive adequate therapeutic benefit from conventional monoaminergic antidepressant drugs, leading to treatment-resistant depression (TRD). Ketamine has been shown to provide rapid and significant efficacy in treating patients with TRD. The majority of published studies have in...
Article
Background The efficacy of monoamine-based antidepressants in adults with major depressive disorder (MDD) is attenuated in persons with greater pre-treatment functional impairment. Herein, we investigated whether pre-treatment functioning in outpatients with treatment-resistant depression (TRD) moderates response to intravenous (IV) ketamine. Meth...
Article
Objective : To compare the mortality risk due to covid-19 with death due to overdose in British Columbia, Canada. The opioid epidemic was declared a public health emergency in 2016. Methods : Mortality risk was calculated in micromorts with covid-19 data for January–October 2020, derived from the BC Centre for Disease Control, and illicit drug tox...
Article
The emerging roles of ketamine and esketamine as effective rapid-acting antidepressants hold promise for patients suffering from treatment-resistant depression and/or major depressive disorder with suicidality. Practitioner familiarity with common tolerability/safety concerns along with pragmatic prevention and management strategies are needed to r...
Article
Importance Preexisting noncommunicable diseases (eg, diabetes) increase the risk of COVID-19 infection, hospitalization, and death. Mood disorders are associated with impaired immune function and social determinants that increase the risk of COVID-19. Determining whether preexisting mood disorders represent a risk of COVID-19 would inform public he...
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We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith–Hamilton Pleasure S...
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Background The COVID-19 pandemic represents a public health, economic and mental health crisis. We hypothesized that timely government implementation of stringent measures to reduce viral transmission would benefit mental health, as evidenced by reduced rates of depressive symptoms (i.e., Patient Health Questionnaire [PHQ]-9≥10, PHQ-2≥3). Methods...
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Objectives Available information exists supporting the gut–brain axis, but additional information is needed to explore how the gut microbiome changes when exposed to mood disorder treatments. We sought to explore the effects of a novel treatment for bipolar disorder (BD), infliximab, on the gut microbiome. Methods Participants with a primary diagn...
Article
Sleep disturbances are commonly reported in patients with treatment-resistant depression (TRD). Available data have shown that intravenous (IV) ketamine is an effective treatment for patients with TRD and growing data suggest ketamine may improve overall sleep architecture. In the present study, we evaluated whether changes in sleep symptoms mediat...
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Background Cognitive deficits are prevalent in bipolar disorder and are a significant contributor to negative patient-reported outcomes. Herein we conducted a pilot study of repetitive transcranial magnetic stimulation (rTMS) to improve cognitive function in adults with bipolar disorder. Methods The study was a triple-blinded, randomized, placebo-...
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Objectives Clinical staging is widely used in medicine to map disease progression, inform prognosis and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurre...
Article
Background: In recent years, ketamine and esketamine treatment have demonstrated rapid antidepressant effects in adults with treatment-resistant depression (TRD). Hitherto, relatively few studies have reported the effect of ketamine/esketamine treatment on functional outcomes (e.g., psychosocial functioning, workplace functioning). Herein, we revi...
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Purpose Benzodiazepines are commonly prescribed globally. We hypothesize that gender stereotypes influence benzodiazepine prescriptions insofar as male prescribers are more likely to prescribe benzodiazepines to female patients. Methods Our nationwide cohort study included 2,127,441 patients with a psychiatric disorder (ICD-9 codes 290–319) and 38...
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Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from...
Article
Ketamine may exert pro-cognitive effects on select measures of cognition in adults with mood disorders. We evaluated the effectiveness of intravenous (IV) ketamine on cognition in 68 adult outpatients with treatment-resistant depression (TRD) at the Canadian Rapid Treatment Center of Excellence between July 3, 2018 and April 16, 2020 (NCT04209296)....
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Intravenous (IV) ketamine has been shown to have rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD). Urological toxicity has been observed in chronic ketamine abusers as evidenced by dysuria, urgency, and hematuria. The foregoing observation provides the basis for evaluating whether ketamine-induced urologic...
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Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatme...
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Background: Depression severity and efficacy measurement scales employed for rapid-onset novel treatments (e.g., ketamine) were initially validated in adults receiving conventional monoamine-based antidepressants. Herein, we provide results validating the McIntyre and Rosenblat Rapid Response Scale (MARRRS). Methods: Adults with treatment-resistant...
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Background The bidirectional association between Major Depressive Disorder (MDD) and obesity suggests that body mass index (BMI) at the baseline could influence remission rates (RR) with pharmacological treatment. We evaluated the influence of baseline BMI on the chances of remission among patients with MDD administered antidepressants. Methods Ba...
Article
Numerous clinical trials have reported that intravenous (IV) ketamine demonstrates rapid antidepressant and anti-suicidal effects in patients with treatment-resistant depression (TRD). These studies, however, have not characterized whether these antidepressant effects translate to improvements in workplace productivity and functionality. Adults wit...
Article
Objective Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation). Methods PsycINFO, Google Scholar...
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Objectives To explore the relationship between inflammation and neuronal metabolism in bipolar disorder (BD) by evaluating the neurochemical effects of the tumor necrosis factor-α (TNF-α) antagonist infliximab among individuals with bipolar depression Methods This is a post-hoc, exploratory analysis from a 12-week, randomized, double-blind, placeb...
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Loneliness is a key determinant in the etiology of mental health disorders such as depression and has profound impacts on health, quality of life, and economic productivity. This narrative review uses extant neurobiology and evolutionary literature to propose a construct through which loneliness may induce depression in adulthood via the reward sys...
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Cognitive impairment is common in bipolar disorder and is emerging as a therapeutic target to enhance quality of life and function. A systematic search was conducted on PubMed, PsycInfo, Cochrane, clinicaltrials.gov, and Embase databases for blinded or open-label randomized controlled trials evaluating the pro-cognitive effects of pharmacological,...
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Background Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD pr...
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Ecological momentary assessment (EMA) for mental disorders, using app-based technology capable of passive and ambient data collection, has been insufficiently evaluated and validated with rigorous, adequately-powered, high-quality studies. Herein, we sought to validate the mind.me application (app) for the assessment of depressive symptoms in adult...
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Replicated evidence has documented cognitive deficits in populations with treatment-resistant depression (TRD). Approximately 40 % of patients with MDD present with impairment of one or more cognitive domains. As such, there is an unmet need to discover treatments that have pro-cognitive effects in TRD patients. Ketamine has demonstrated efficacy a...
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The emergence of ketamine as a rapid-action treatment for depression provided the impetus for the investigation of several new agents to address this unmet need. Pharmacologic targets from ketamine became a focus of interest. Strategies for development of new rapid-action agents include the manipulation of ketamine targets and also repurposing drug...
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Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma...
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Background Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation...
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Background Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD). Methods Adults (N = 230) with TRD received four infusions of IV ketamine at...
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The primary objective was to evaluate the comparative effects of loneliness on multiple distinct health outcomes. The literature was qualitatively reviewed to identify loneliness risk factors, explore mechanisms, and discuss potential evidence-based interventions for targeting loneliness. 114 identified studies were systematically reviewed and anal...
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The efficacy of ketamine in reducing suicidal ideation (SI) has been previously reported. We aimed to evaluate acute anti-SI effects of single-dose ketamine in different formulations/routes of administration by pooling results from randomized controlled trials (RCTs). A systematic search was conducted on Cochrane, Embase, Medline, and PubMed from i...
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Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are asso...
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Background : To assess the effect of insulin resistance (IR) on treatment response to the antidepressant, vortioxetine, in patients with Major Depressive Disorder (MDD). Methods : This is a secondary analysis of an 8-week, open-label clinical trial. Ninety-five adults in a primary care setting experiencing a major depressive episode were included....
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Background Dissociation is a treatment-emergent adverse event commonly associated with IV ketamine, often measured using the 23-item Clinician-Administered Dissociative States Scale (CADSS). The objective of this study was to develop a short form version of the CADSS for easier clinical use. Methods Retrospective data of 260 patients with treatmen...
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Antidepressant medications are the first‐line treatment option for moderate to severe major depressive disorder. However, most antidepressants have numerous documented adverse events, including cardiometabolic effects and weight gain, which are major public health concerns. Antidepressant agents provide varying risk of associated weight gain, inclu...
Article
Background: Individuals meeting criteria for treatment-resistant depression (TRD) are differentially affected by high levels of anxiety symptoms. Aims: There is a need to identify the efficacy of novel rapid-onset treatments in adults with mood disorders and comorbid anxious-distress. Methods: This study included patients with treatment-resistant...
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Background: Early symptomatic improvement with monoamine-based antidepressants is predictive of treatment response. The objective of this study was to determine if early symptomatic improvements with intravenous (IV) ketamine predicted treatment response to an acute course of four infusions. Method: 134 adults with treatment resistant depression (...
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Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures...
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Introduction: Mental illness has a chronic course of illness with a number of clinical manifestations. Affected individuals experience significant functional, emotional, cognitive and/or behavioral impairments. The growing prevalence of mental illness has been associated with significant social and economic costs. Indeed, the economic burden of me...
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Women are disproportionately represented amongst samples of adults with treatment-resistant depression (TRD). Ketamine has demonstrated rapid and robust efficacy in adults with TRD. Herein, we sought to determine whether the effectiveness of intravenous (IV) ketamine was influenced by menopausal status in women with TRD. We defined premenopausal wo...
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Objective Fibromyalgia (FM) is a condition associated with chronic pain in muscles and soft tissues. Extant literature has demonstrated an association between FM, mood symptoms and suicidal behaviour. This systematic review aims to synthesize available literature assessing the prevalence of suicidality in FM populations and qualitatively review the...
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Background Anhedonia is a trans-diagnostic, multidimensional phenotype that mediates patient outcomes and suicidality. Convergent evidence suggests that ketamine may be effective in targeting measures of anhedonia in adults with treatment resistant depression (TRD). Methods This retrospective, post-hoc analysis included 203 (x̄ = 45 ± 14.6 years o...
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Numerous pharmacological treatments for mood disorders are currently available; however, rates of treatment resistance, relapse and recurrence remain high. Therefore, novel treatments acting outside of the conventionally targeted monoamine system are urgently needed to improve patient outcomes. Emerging and converging evidence suggests that immune...
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Background Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes. Methods: Effect size with respect to depression symptom reduction for each formulation and route of delive...
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Objectives Rigorous clinical trials suggest ketamine is safe and well-tolerated in patients with treatment-resistant depression (TRD). There is a paucity of data on the safety and tolerability of ketamine in community-based clinics treating patients with TRD. Methods Retrospective data was analyzed from 203 patients with TRD who received repeat-do...
Article
A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-α) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-α system. Herein, we aimed to explore infliximab’s effects on leptin and...
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Background Herein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized antidepressant therapy.Methods Adults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Å...
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We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activi...
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Background : The effectiveness, tolerability, and safety of IV ketamine in adults with treatment resistant depression (TRD) receiving care in real-word settings is insufficiently characterized. Herein, results from a naturalistic, retrospective study are presented from an outpatient off-label Canadian IV ketamine clinic. Methods : Adults (N = 213;...
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Objective To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment‐resistant major depressive disorder (MDD) or bipolar disorder (BD). Method Adults (N = 201) with treatment‐resistant MDD or BD received repeat‐dose IV ketamine treatment at a community‐based clinic. M...
Article
Physical activity (PA) has been proposed as a determinant of cognitive function and is one component of energy balance (EB). EB is the difference between energy intake (EI) and the total daily energy expenditure (TDEE). TDEE is a combination of resting metabolic rate (RMR), thermic effect of food and PA. The potential role of each of these componen...
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The objective of the current study was to assess the association between adverse childhood experiences (ACE) and irritable bowel syndrome (IBS) in mood disorder patients. Self-report data from the International Mood Disorders Collaborative Project were cross-sectionally analyzed to compare rates of IBS in participants with confirmed diagnoses of ma...
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Accumulating evidence suggests that neuroinflammation is involved in bipolar disorder (BD) pathogenesis. The tumor necrosis factor-alpha (TNF-α) antagonist infliximab was recently reported to improve depressive symptoms in a subpopulation of individuals with BD and history of childhood maltreatment. To explore the mechanistic mediators of inflixima...
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Advances in the understanding and management of bipolar disorder (BD) have been slow to emerge. Despite notable recent developments in neurosciences, our conceptualization of the nature of this mental disorder has not meaningfully progressed. One of the key reasons for this scenario is the continuing lack of a comprehensive disease model. Within th...