53 results on '"Lee, Yena"'
Search Results
2. Effects of liraglutide on depressive behavior in a mouse depression model and cognition in the probe trial of Morris water maze test.
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Seo MK, Jeong S, Seog DH, Lee JA, Lee JH, Lee Y, McIntyre RS, Park SW, and Lee JG
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- Mice, Animals, Depression drug therapy, Maze Learning, Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Cognition, Glucagon-Like Peptide 1, Disease Models, Animal, Behavior, Animal, Stress, Psychological, Liraglutide pharmacology, Liraglutide therapeutic use, Morris Water Maze Test
- Abstract
Background: We investigated the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, on a depression-like phenotype in mice exposed to chronic unpredictable stress (CUS). Learning and memory were also assessed using the Morris water maze (MWM) test., Methods: Liraglutide (0.3 mg/kg/day for 21 days) was administered to mice with or without exposure to CUS. After 21 days of CUS, the forced swim test (FST) was performed to assess its antidepressant effect. To evaluate cognitive function, liraglutide was administered to mice under stress-free conditions for 21 days, and then the MWM test was performed on 6 consecutive days., Results: Chronic liraglutide treatment reduced FST immobility in mice with and without CUS. In the probe trial of the Morris water maze test, the search error rate was reduced and the time spent and path length in the target quadrant and the number of platform crossings were increased., Limitation: Additional animal model experiments and molecular level studies are needed to support the results obtained in this study., Conclusions: Liraglutide appears to exert antidepressant effects and could improve cognitive function. Based on these results, GLP-1 agonists could have potential as novel antidepressants., Competing Interests: Conflict of interest Dr. Roger McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC); speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2023
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3. The association between stage of treatment-resistant depression and clinical utility of ketamine/esketamine: A systematic review.
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Levinta A, Meshkat S, McIntyre RS, Ho C, Lui LMW, Lee Y, Mansur RB, Teopiz KM, Rodrigues NB, Di Vincenzo JD, Ceban F, and Rosenblat JD
- Subjects
- Antidepressive Agents therapeutic use, Depression drug therapy, Humans, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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 search of PubMed and Scopus from inception to August 2021 was conducted. Where applicable, the studies were categorized into low and high stages of resistance, where low category included studies where the mean number of failed antidepressants was <3 or had a higher proportion of subjects with ≤2 antidepressant trials. Reported indicators of treatment resistance and efficacy were extracted from randomized-controlled trials (RCTs) assessing ketamine or esketamine for TRD., Results: In total, 18 RCTs were included in the current review. There was variability across reported indicators of disease severity, definition of treatment resistance, as well as treatment protocols, preventing clear direct and indirect comparison of relative efficacy of ketamine at different stages of treatment resistance. Ketamine was effective in reducing depressive symptoms in RCTs at both lower and higher stages of treatment resistance; however, the effect size and duration of effects was greater in RCTs of lower stage of treatment resistance., Conclusions: Our findings suggested that ketamine has antidepressant efficacy across all identified stages of treatment resistance, however with increasing failed treatment trials, treatment might be less efficacious. At this time, the comparative efficacy as a function of resistance stage remains to be well-established. Evaluation of participant level data is required to more clearly determine the association between level of treatment resistance and likelihood of response., Competing Interests: Conflict of Interest Dr. Roger S. McIntyre has received research grant support from Global Alliance for Chronic Diseases/Canadian Institutes of Health Research (CIHR)/National Natural Science Foundation of China's Mental Health Team Grant; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Dr. Joshua D. Rosenblat is the medical director of Braxia Health (formally known as the Canadian Rapid Treatment Center of Excellence and is a fully owned subsidiary of Braxia Scientific Corp) and Chief Medical & Scientific Officer of Braxia Scientific Corp which provides ketamine and esketamine treatment for depression; he has received research grant support from the American Psychiatric Association, the American Society of Psychopharmacology, the Canadian Cancer Society, the Canadian Psychiatric Association, the Joseph M. West Family Memorial Fund, the Timeposters Fellowship, the University Health Network Centre for Mental Health, and the University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. Yena Lee has received personal fees from Braxia Scientific Corp. Leanna M. W. Lui is a contractor to Braxia Scientific Corp. Nelson B Rodrigues has received consulting fees from Braxia Scientific Corp. Joshua D. Di Vincenzo is a consultant to Braxia Scientific Corp., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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4. Impact of cognitive-affective and somatic symptoms in subthreshold depression transition in adults: Evidence from Depression Cohort in China (DCC).
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Liao Y, Zhang H, Guo L, Fan B, Wang W, Teopiz KM, Lui LMW, Lee Y, Li L, Han X, Lu C, and McIntyre RS
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- Adult, Cognition, DCC Receptor, Depression diagnosis, Depression epidemiology, Depression etiology, Humans, Depressive Disorder, Major, Medically Unexplained Symptoms, Sleep Initiation and Maintenance Disorders diagnosis, Sleep Initiation and Maintenance Disorders epidemiology
- Abstract
Background: Symptoms of subthreshold depression may differentially affect the illness transition. We examined the impact of cognitive-affective and somatic symptoms on different subthreshold depression transitions as well as risk factors influencing the aforementioned symptoms changes., Methods: Adults with subthreshold depression in the Depression Cohort in China were enrolled. Data collection was conducted at baseline, 6 and 12 months from 2019 to 2020. Cognitive-affective and somatic symptoms were assessed using the Patient Health Questionnaire-9. A total of 993 participants completed 12-month follow-up and were divided into persistent, intermittent and remission groups according to change in depressive symptoms. The longitudinal change of cognitive-affective and somatic symptoms in the three groups, as well as risk factors was analyzed using the generalized linear mixed-model., Results: There were 24.07 %, 34.04 % and 41.89 % of participants proceeding into persistent, intermittent and remission subthreshold depression groups, respectively. Cognitive-affective symptoms were the core symptoms for predicting the deterioration in persistent subthreshold depression (t = 2.48, P = 0.013), whereas somatic symptoms improved over time (t = -2.82, P = 0.005). Anxiety symptoms were the primary risk factors for worsening cognitive-affective symptoms (P < 0.001), following by insomnia symptoms, age, marital status, resilience and social functions. Somatic symptoms were affected by insomnia symptoms, anxiety symptoms and Body Mass Index successively., Limitations: Major Depressive Episode was not explored in follow-up., Conclusion: Cognitive-affective symptoms in subthreshold depression are at greater risk of illness deterioration. Future studies should endeavor to identify specific risk factors in different symptoms to forestall the transition from subthreshold to Major Depressive Disorder., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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5. Active mechanisms of ketamine-assisted psychotherapy: A systematic review.
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Joneborg I, Lee Y, Di Vincenzo JD, Ceban F, Meshkat S, Lui LMW, Fancy F, Rosenblat JD, and McIntyre RS
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- Adult, Humans, Psychotherapy, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine
- Abstract
Background: Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD)., Methods: A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo., Results: Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit., Limitations: Lack of large, replicated clinical trials. No studies actively examining mechanisms of action., Conclusion: Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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6. Sex differences in ketamine's therapeutic effects for mood disorders: A systematic review.
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Benitah K, Siegel AN, Lipsitz O, Rodrigues NB, Meshkat S, Lee Y, Mansur RB, Nasri F, Lui LMW, McIntyre RS, and Rosenblat JD
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- Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Female, Humans, Male, Mood Disorders drug therapy, Sex Characteristics, Sex Factors, Ketamine pharmacology, Ketamine therapeutic use
- Abstract
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 females remains underexplored. The objective of the present systematic review is to identify and qualitatively synthesize all published clinical studies relevant to the sex differential effects of ketamine for mood disorders. A systematic search of PubMed, Medline, and PsycInfo from inception until January 20, 2021, yielded 27 reports including 1715 patients (742 males and 973 females) that met inclusion criteria. Results from the vast majority of studies (88.8%) do not support significant sex differences in antidepressant response, tolerability or safety of ketamine. Nine (33.3%) of the reports included a bioanalytical component in the analysis and only one reported on sex differences. Evidence from the present review does not support clinically or statistically significant sex differences in therapeutic effects with ketamine. Nevertheless, future studies should continue to consider sex and biological sex differences in study design and data analytic plans., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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7. Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: A systematic review and meta-analysis.
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Liu YK, Ling S, Lui LMW, Ceban F, Vinberg M, Kessing LV, Ho RC, Rhee TG, Gill H, Cao B, Mansur RB, Lee Y, Rosenblat J, Teopiz KM, and McIntyre RS
- Subjects
- Blood Glucose, Fasting, Glucose, Humans, Obesity complications, Obesity, Abdominal epidemiology, Prevalence, Bipolar Disorder complications, Bipolar Disorder epidemiology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology
- Abstract
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., Methods: A systematic search of Embase, Medline, PubMed, and APA PsycArticles was conducted from inception to June 2021 without language restrictions. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) modified for case-control studies., Results: A total of forty-nine studies were included in this analysis. The pooled prevalence of T2DM was 9.6% (95% CI, 7.3-12.2%). Patients with BD had a nearly 1.6 times greater risk of developing T2DM compared to their age- and gender-matched controls (RR=1.57, 95% CI 1.36-1.81, p<0.001). In the present analysis, IFG is defined as a fasting plasma glucose (FPG) ≥ 100 mg/dL (FPG≥100) with a prevalence of 22.4% (95% CI, 16.7-28.7%), or as an FPG equal to or greater than 110 mg/d (FPG≥110) with a prevalence of 14.8% (95% CI, 10.8-19.3%). The prevalence of general obesity (BMI≥30 kg/m
2 ) was 29.0% (95% CI, 22.8-35.6%); the risk of obesity was almost twice the rate reported in patients with BD compared to controls (RR=1.67, 95% CI 1.32-2.12, p<0.001). We also observed that more than half of the BD participants had abdominal obesity (i.e., prevalence of 51.1%; 95% CI, 45.0-57.3%)., Limitations: A significant degree of heterogeneity was detected. Sources of heterogeneity included differences in study designs, inclusion criteria, measurement tools, and data analysis methods., Conclusion: Bipolar disorder is associated with a higher prevalence of T2DM, IFG, general obesity, and abdominal obesity. Type 2 diabetes mellitus and obesity are significantly more prevalent in patients with BD than in their age- and gender-matched controls., Study Registration: CRD42021258431., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2022
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8. What not to use in bipolar disorders: A systematic review of non-recommended treatments in clinical practice guidelines.
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Gomes FA, Cerqueira RO, Lee Y, Mansur RB, Kapczinski F, McIntyre RS, Yatham LN, Berk M, Milev R, and Brietzke E
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- Antidepressive Agents therapeutic use, Humans, Lamotrigine therapeutic use, Risperidone therapeutic use, Antipsychotic Agents therapeutic use, Bipolar Disorder drug therapy
- Abstract
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 recommendations on pharmacological interventions with evidence against their use due to lack of efficacy data and/or due to serious safety concerns., Methods: A systematic literature search identified 29 guidelines published by national and international organizations during the 1994-2020 period. Information was extracted regarding how the recommendations framed non-use of treatments in particular clinical situations as well as the actual recommendation in the guideline., Results: Twenty-three guidelines (79%) mentioned at least one non-recommended treatment. The terms used to qualify recommendations varied amongst guidelines and included: "not recommended" "no recommendation" and "negative evidence". Lamotrigine, topiramate and gabapentin were commonly cited as non-recommended treatments for mania and most CPG did not recommend monotherapy with antidepressants, aripiprazole, risperidone, and ziprasidone for treatment of acute bipolar depression. Most guidelines made recommendations about lack of efficacy data or potential harm in treatments for BD but there is a significant variation in the way this information is conveyed to the reader., Limitations: Non-recommended treatments were based on their use for BD episodes or maintenance but specific medications may benefit patients when treating comorbid conditions., Conclusions: The absence of a uniform language and recommendations in current guidelines may be an additional complicating factor in the implementation of evidence-based treatments in BD., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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9. Comparing mortality from covid-19 to mortality due to overdose: A micromort analysis.
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Lee Y, Lui LMW, Brietzke E, Liao Y, Lu C, Ho R, Subramaniapillai M, Mansur RB, Rosenblat JD, and McIntyre RS
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- Aged, British Columbia epidemiology, Humans, Pandemics, SARS-CoV-2, COVID-19, Drug Overdose epidemiology
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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 center for Disease Control, and illicit drug toxicity deaths for January 2010-September 2020, derived from the BC Coroners Service. Age-stratified covid-19 incidence and deaths per 100,000 population and age-stratified illicit drug toxicity death rates per 100,000 population were calculated. A micromort is a unit of risk equivalent to a one-in-a-million chance of death., Results: During the covid-19 pandemic, illicit drug toxicity deaths reached 1.0 micromorts per day, representing an increase of 0.5 micromorts per day relative to 2019 rates. In comparison, covid-19 mortality risk was 0.05 micromorts per day among individuals from the general population living in British Columbia and 21.1 micromorts per day among those infected with covid-19. Covid-related mortality risk was significantly lower among individuals aged <60 years, relative to older adults, whereas drug toxicity-related mortality was highest for individuals aged 30-59 years., Conclusions: The mortality associated with covid-19 is apparent and distributed unevenly across subpopulations. The mortality due to overdose has increased during covid-19 and exceeds mortality due to covid-19. Our results instantiate the triple threat caused by covid-19 (i.e., public health crisis, economic crisis and mental health crisis) and quantitatively highlight the externality of increased mortality due to deaths of despair in response to public health efforts to reduce covid-related mortality., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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10. Frequency analysis of symptomatic worsening following ketamine infusions for treatment resistant depression in a real-world sample: Results from the canadian rapid treatment center of excellence.
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Di Vincenzo JD, Lipsitz O, Rodrigues NB, Jones BDM, Gill H, Lee Y, Lui LMW, Teopiz KM, Ho R, Lin K, Nasri F, McIntyre RS, and Rosenblat JD
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- Adult, Canada epidemiology, Humans, Infusions, Intravenous, Middle Aged, Retrospective Studies, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine adverse effects
- Abstract
Antidepressants are associated with symptomatic worsening in a subgroup of patients. Replicated evidence has demonstrated rapid and robust antidepressant effects with intravenous (IV) ketamine in treatment resistant depression (TRD); however, the risk of ketamine worsening depressive symptoms in a subgroup of patients remains unknown. Herein we report a retrospective analysis on the rates of symptomatic worsening during an acute course of IV ketamine in individuals with unipolar (n = 142) and bipolar (n = 22) TRD. Adults (N = 164; mean age = 45.97) with TRD underwent four sub-anesthetic infusions (0.5-0.75 mg/kg over 40 min) of IV ketamine over two weeks, and were assessed with the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR
16 ) at baseline and after each infusion. The primary outcome was the proportion of patients experiencing clinically significant worsening of depressive symptoms (≥20% increase on the QIDS-SR16 ) at each time point relative to baseline. Secondary analyses explored trends in the results. The frequency of clinically significant worsening fluctuated between 1.83% to 5.49%, with no identifiable trend across time. Zero individuals with bipolar TRD reported symptomatic worsening. Limitations include the single-centered, uncontrolled, retrospective nature of this study. Rates of symptomatic worsening associated with IV ketamine therapy for TRD appear to be very low and similar to conventional antidepressants., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2022
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11. Ketamine for psychotic depression: An overview of the glutamatergic system and ketamine's mechanisms associated with antidepressant and psychotomimetic effects.
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Le TT, Di Vincenzo JD, Teopiz KM, Lee Y, Cha DS, Lui LMW, Rodrigues NB, Ho RC, Cao B, Lin K, Nasri F, Gill H, Lipsitz O, Subramaniapillai M, Mansur RB, Rosenblat JD, and McIntyre RS
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- Antidepressive Agents adverse effects, Depression drug therapy, Humans, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Ketamine adverse effects
- Abstract
Approximately 0.35-1% 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 mortality rate. Although treatment guidelines recommend a combination of antidepressants and antipsychotics or electroconvulsive therapy, most patients subsequently relapse due to treatment resistance. Furthermore, with the concern of antipsychotic drug's side effects (e.g., tardive dyskinesia), there is a need for an alternative pharmacotherapy for psychotic depression. Recently, several case studies demonstrated that treatment with ketamine not only ameliorated mood, but also improved psychotic symptoms in patients with treatment-resistant depression and psychotic features. However, the safety of ketamine in these patients is controversial since ketamine is known to induce psychotomimetic and dissociative effects. Additionally, the efficacy and safety of ketamine in patients with psychotic depression has not been established as most clinical trials have excluded these persons due to the theorized risk of aggravating psychotic symptoms. Notwithstanding, it is not established empirically that ketamine treatment in psychotic depression would predictably amplify psychotic symptoms and/or overall illness presentation. Future trials evaluating ketamine in depression should include patients with psychotic features to inform whether ketamine is safe and effective in this subpopulation., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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12. The meaningful change threshold as measured by the 16-item quick inventory of depressive symptomatology in adults with treatment-resistant major depressive and bipolar disorder receiving intravenous ketamine.
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McIntyre RS, Lipsitz O, Lui LMW, Rodrigues NB, Gill H, Nasri F, Ling R, Teopiz KM, Ho RC, Subramaniapillai M, Kratiuk K, Mansur RB, Jones BDM, Lee Y, and Rosenblat JD
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- Adult, Humans, Psychiatric Status Rating Scales, Self Report, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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 used to identify meaningful change on the patient-reported Quick Inventory for Depressive Symptoms Self-Report 16-Item (QIDS-SR16) as associated with the Patient Global Impression - Severity (PGI-S). Both the QIDS-SR16 and the PGI-S are self-report measures, and were collected at five timepoints (timepoints were approximately 2-7 days apart)., Results: .A total of 297 adults with treatment-resistant depression (TRD) as part of either DSM-5-defined MDD or BD were included. The MCT for the QIDS-SR16 revealed that a mean improvement of 3.38 points from baseline was comparable to a 1-point improvement on the PGI-S. Together with an examination of the probability density function, a 3.5-point change is a reasonable MCT (i.e., 1-point PGI-S improvement) for the QIDS-SR16. A 2-point symptomatic improvement on the QIDS-SR16 was associated with no change on the PGI-S., Conclusion: .A 3.5-point reduction in the QIDS-SR16 represents a MCT based on the PGI-S for adults with treatment-resistant MDD or BD receiving intravenous ketamine treatment at a community-based mood disorders center. These findings are limited by the post-hoc nature of this analysis and open-label case-series design. Measurement-based care decisions by patients, providers and clinicians, as well as cost/reimbursement decisions should include consideration of meaningful change along with conventional objective outcomes., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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13. Efficacy of ketamine and esketamine on functional outcomes in treatment-resistant depression: A systematic review.
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Ng J, Rosenblat JD, Lui LMW, Teopiz KM, Lee Y, Lipsitz O, Mansur RB, Rodrigues NB, Nasri F, Gill H, Cha DS, Subramaniapillai M, Ho RC, Cao B, and McIntyre RS
- Subjects
- Adult, Antidepressive Agents therapeutic use, Depression, Humans, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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 review and synthesize extant literature reporting functional outcomes with ketamine/esketamine treatment in adults with TRD., Methods: A systematic review of clinical studies reporting subjective or objective ratings of general functioning as primary or secondary outcomes was performed., Results: Four randomized-controlled trials, one open-label clinical study and one case series reported on the efficacy of ketamine/esketamine on subjective measures of general functioning. Overall, mixed results were reported with respect to the effect across disparate functional measures (e.g., Sheehan Disability Scale [SDS]) using ketamine/esketamine. A single study demonstrated a significant decrease (i.e., improvement) in SDS total scores in TRD with esketamine treatment; most studies, however, did not report on functional outcomes and have functional outcomes as a (co)-primary outcome measure., Limitations: Clinical studies that were included evaluated work- or social-related disability as a secondary outcome using subjective rating scales., Conclusion: Functional outcomes in adults with TRD receiving ketamine/esketamine was insufficiently characterized. Available evidence indicates that improvements in general psychosocial functioning is apparent. The association, if any, between symptomatic improvement and functional improvement in TRD, as well as the temporality to improve functioning, are future research vistas., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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14. Repetitive transcranial magnetic stimulation for cognitive function in adults with bipolar disorder: A pilot study.
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McIntyre RS, Lee Y, Rodrigues NB, Nasri F, Lao G, Zeng W, Ye B, Li R, Rosenblat JD, Mansur RB, Subramaniapillai M, Lui LMW, Teopiz KM, Liu T, Xiong J, Zhang R, Lu W, Xu G, Huang X, and Lin K
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- Adult, Cognition, Humans, Pilot Projects, Transcranial Magnetic Stimulation, Bipolar Disorder therapy, Schizophrenia
- Abstract
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-control trial. Participants (aged 18 to 60) with a diagnosis of DSM-5-defined bipolar disorder (I or II) were recruited and randomized (N=36) to receive either a sham treatment (n=20) or an active rTMS treatment (n=16). Patients completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at baseline and 1-2 weeks after the rTMS intervention., Results: A significant group by time interaction was observed in the Hopkins Verbal Learning Test-Revised (HVLT-R), (F (1, 34) = 17.0, p < 0.001, partial η
2 = 0.33). Post-hoc analysis revealed that although both groups did not significantly differ at baseline (p = 0.58), patients in the active rTMS group significantly improved following neurostimulation (p = 0.02) for HVLT-R. Moreover, within-subject analysis indicated that the active rTMS group significantly improved in score from pre-treatment to post-treatment (p < 0.001), while the sham group did not improve (p = 0.94) for HVLT-R. No significant differences were seen in the other cognitive measures., Limitations: The study was conducted in a small sample ., Conclusion: This pilot study, which was intended to establish feasibility, suggests that rTMS may offer benefit in select domains of cognitive functioning in bipolar disorder. None of the measures across subdomains revealed a dyscognitive effect., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2021
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15. Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic.
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Rosenblat JD, Lipsitz O, Di Vincenzo JD, Rodrigues NB, Kratiuk K, Subramaniapillai M, Lee Y, Arekapudi AK, Abrishami A, Chau EH, Szpejda W, Wong L, Mansur RB, and McIntyre RS
- Subjects
- Adult, Depression, Humans, Infusions, Intravenous, Ontario, Pandemics, SARS-CoV-2, COVID-19, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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 March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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16. Does pre-treatment functioning influence response to intravenous ketamine in adults with treatment-resistant depression?
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McIntyre RS, Lipsitz O, Lui LMW, Rodrigues NB, Lee Y, Ho RC, Subramaniapillai M, Gill H, Cha DS, Lin K, Teopiz KM, Nasri F, Mansur RB, Kratiuk K, and Rosenblat JD
- Subjects
- Adult, Depression, Humans, Infusions, Intravenous, Middle Aged, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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., Methods: Adults (N= 326; M
age = 45) with DSM-5-defined MDD or bipolar disorder and TRD received repeat-dose IV ketamine at a community-based clinic. Function was evaluated with the Sheehan Disability Scale (SDS), using total scores as well as scores on the subdomains of workplace/school, social life, and family life/home responsibilities. The primary dependent measure was change in depressive symptoms from pre-treatment to post-infusion 4, as measured by the Quick Inventory for Depressive Symptomatology-Self Report-16., Results: Total functional disability, as well as the subdomains of social life and family life/home responsibilities, significantly moderated response to IV ketamine (p = .003; p = .008; p = .008). Follow-up simple slopes analyses indicated a significant improvement in depressive symptoms across the functional domain spectrum (ps < .001). Above average functional disability (i.e., 1 SD > mean functional impairment within the sample) was associated with a greater change in depressive symptoms. Workplace function did not significantly moderate response to IV ketamine (p = .307), suggesting that individuals with significantly impaired workplace functioning may expect a similar response to ketamine as those with less workplace impairment., Conclusions: Symptomatic benefit with IV ketamine was observed in patients with TRD and significant pre-treatment functional impairment. The foregoing result has implications for mechanism of action, cost-effectiveness, and patient selection in adults with TRD receiving IV ketamine., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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17. The effect of intravenous ketamine on cognitive functions in adults with treatment-resistant major depressive or bipolar disorders: Results from the Canadian rapid treatment center of excellence (CRTCE).
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McIntyre RS, Rosenblat JD, Rodrigues NB, Lipsitz O, Chen-Li D, Lee JG, Nasri F, Subramaniapillai M, Kratiuk K, Wang A, Gill H, Mansur RB, Ho R, Lin K, and Lee Y
- Subjects
- Adult, Canada, Cognition, Humans, Infusions, Intravenous, Retrospective Studies, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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). Eligibility criteria for the present retrospective study included: primary diagnosis of major depressive or bipolar disorder; currently depressed; and insufficient response to two or more prior treatments. Participants received four infusions of ketamine hydrochloride (0.5-0.75 mg/kg) over 1-2 weeks. We assessed objective and subjective measures of cognition before and after two infusions, i.e., Digit Symbol Substitution Test (DSST), Trail Making Test-B (TMT-B), Patient Deficits Questionnaire, 5-item (PDQ-5-D). Ketamine significantly improved DSST (effect size [ES]=0.60), TMT-B (ES=0.84), as well as PDQ-5-D scores (ES=0.63), indicative of a moderate-to-large effect size. Improvements in DSST and PDQ-5-D with ketamine were mediated by reductions in depressive symptoms, whereas improvements in TMT-B were independent of changes in depressive symptoms. Our results support the independent, rapid-onset, pro-cognitive effects with IV ketamine in adults with TRD. Larger, randomized, controlled trials with ketamine wherein cognition is the primary outcome measure in mood and non-mood disorder samples are warranted., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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18. Government response moderates the mental health impact of COVID-19: A systematic review and meta-analysis of depression outcomes across countries.
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Lee Y, Lui LMW, Chen-Li D, Liao Y, Mansur RB, Brietzke E, Rosenblat JD, Ho R, Rodrigues NB, Lipsitz O, Nasri F, Cao B, Subramaniapillai M, Gill H, Lu C, and McIntyre RS
- Subjects
- Communicable Disease Control, Depression epidemiology, Government, Humans, Mental Health, Retrospective Studies, SARS-CoV-2, COVID-19, Pandemics
- Abstract
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: The systematic review herein (PROSPERO CRD42020200647) evaluated to what extent differences in government-imposed stringency and timeliness of response to COVID-19 moderate the prevalence of depressive symptoms across 33 countries (k=114, N=640,037). We included data from six lower-middle-income countries, nine upper-middle-income countries, and 18 higher-income countries. Government-imposed stringency and timeliness in response were operationalized using the Oxford COVID-19 Government Response ("Stringency") Index., Results: The overall proportion of study participants with clinically significant depressive symptoms was 21.39% (95% CI 19.37-23.47). The prevalence of clinically significant depressive symptoms was significantly lower in countries wherein governments implemented stringent policies promptly. The moderating effect of government response remained significant after including the national frequency of COVID cases at the time of study commencement, Healthcare Access and Quality index, and the inclusion of COVID patients in the study., Limitations: Factors that may have confounded our results include, for example, differences in lockdown duration, lack of study participant and outcome assessor blinding, and retrospective assessment of depressive symptom severity., Conclusions: Governments that enacted stringent measures to contain the spread of COVID-19 benefited not only the physical, but also the mental health of their population., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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19. The effect of repeated doses of intravenous ketamine on measures of workplace attendance and productivity in adults with major depressive and bipolar disorder: Results from the canadian rapid treatment center of excellence.
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Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Subramaniapillai M, Kratiuk K, Majeed A, Nasri F, Gill H, Mansur RB, and Rosenblat JD
- Subjects
- Adult, Canada, Humans, Infusions, Intravenous, Workplace, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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 with TRD received repeated doses of IV ketamine at a community-based clinic (n = 171). We evaluated patient outcomes at two timepoints of interest: (1) acute-phase (i.e., following 4-6 infusions, 17.6 ± 12.6 days from baseline) and (2) maintenance-phase (i.e., following 7-10 infusions, 153.9 ± 63.4 days from baseline). The primary outcome measure was change from baseline to maintenance-phase scores on the Sheehan Disability Scale (SDS) workplace/school item as well as days underproductive (i.e., presenteeism) and days lost (i.e., absenteeism). Secondary measures included the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR
16 ). There was a significant reduction in workplace/school disability, and significantly reduced symptoms of presenteeism and absenteeism. At the acute-phase outcome, this translated to 2 more days of productivity and 1.5 less days absent from work. Additionally, IV ketamine exhibited a sustained antidepressant effect across the ten infusions. IV ketamine was associated with a significant reduction in workplace/school disability and demonstrated improvements in symptoms of presenteeism and absenteeism., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2021
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20. Validation of the McIntyre And Rosenblat Rapid Response Scale (MARRRS) in Adults with Treatment-Resistant Depression Receiving Intravenous Ketamine Treatment.
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McIntyre RS, Rodrigues NB, Lipsitz O, Lee Y, Cha DS, Gill H, Lui LMW, Subramaniapillai M, Kratiuk K, Ho R, Mansur RB, and Rosenblat JD
- Subjects
- Adult, Antidepressive Agents therapeutic use, Depression, Humans, Infusions, Intravenous, Middle Aged, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
Background: Depression severity and efficacy measurement scales employed for rapid-acting treatments (e.g., ketamine) were initially validated in adults receiving conventional monoamine-based antidepressants. The emergence of rapid-acting antidepressants in psychiatry provides the impetus for outcome measures that have been validated as sensitive to change with rapid-acting treatments. Herein, we provide results validating the McIntyre and Rosenblat Rapid Response Scale (MARRRS)., Methods: Adults with treatment-resistant depression (TRD) receiving intravenous (IV) ketamine had depressive symptoms measured with the 16-Item Quick Inventory Depressive Symptoms Self-Report (QIDS-SR-16) and MARRRS at baseline and as a repeated measure across an acute course of four infusions. The MARRRS is a self-report measure assessing depressive symptoms during the past 72 hours., Results: Sixty-four patients (M
age = 45.4 ± 13.5) were included. The MARRRS had a high internal consistency across acute infusions as determined by Cronbach's alpha (0.84 to 0.94). There was significant convergent validity between the QIDS-SR-16 and MARRRS total scores across infusions (rs(292) = .87, p < .001); the MARRRS was also sensitive to change (rs(49) = .70, p < .001). Exploratory factor analysis revealed that MARRRS items loaded onto two factors (i.e., dysphoria and psychic anxiety) accounting for 63.4% of the total variance., Limitations: Heterogenous sample of adults with TRD receiving open-label treatment without placebo comparison., Conclusion: The MARRRS is a brief validated self-report metric of depression symptom severity that is sensitive to change with the rapid-acting antidepressant ketamine. Measuring outcomes with the MARRRS informs treatment progress and facilitates treatment decisions in persons receiving the rapid-acting antidepressant ketamine. Studies of other rapid-acting antidepressants should incorporate outcome measures that are validated as sensitive to change with rapid-acting antidepressants., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2021
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21. A Systematic review of the validity of screening depression through Facebook, Twitter, Instagram, and Snapchat.
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Kim J, Uddin ZA, Lee Y, Nasri F, Gill H, Subramanieapillai M, Lee R, Udovica A, Phan L, Lui L, Iacobucci M, Mansur RB, Rosenblat JD, and McIntyre RS
- Subjects
- Depression diagnosis, Emotions, Friends, Humans, Linguistics, Social Media
- Abstract
Background: The aim of this study was to determine the validity of using social media for depression screening., Method: Article searches on PubMed and PsycINFO from database inception to August 20, 2019 were completed with a search string and filters., Results: 15 articles made the inclusion criteria. Facebook, Twitter, and Instagram profiles of depressed people were distinguishable from nondepressed people shown by social media markers. Facebook studies showed that having fewer Facebook friends and mutual friends, posting frequently, and using fewer location tags positively correlated with depressive symptoms. Also, Facebook posts with explicit expression of depressive symptoms, use of personal pronouns, and words related to pain, depressive symptoms, aggressive emotions, and rumination predicted depression. Twitter studies showed that the use of "past focus" words, negative emotions and anger words, and fewer words per Tweet positively correlated with depression. Finally, Instagram studies showed that differences in follower patterns, photo posting and editing, and linguistic features between depressed people and nondepressed people could serve as a marker., Limitations: The primary articles analyzed had different methods, which constricts the amount of comparisons that can be made. Further, only four social media platforms were explored., Conclusion: Social media markers like number and content of Facebook messages, linguistic variability in tweets and tweet word count on Twitter, and number of followers, frequency of Instagram use and the content of messages on Instagram differed between depressed people and nondepressed people. Therefore, screening social media profiles on these platforms could be a valid way to detect depression., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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22. Loneliness-based impaired reward system pathway: Theoretical and clinical analysis and application.
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Wilkialis L, Rodrigues N, Majeed A, Lee Y, Lipsitz O, Gill H, Tamura J, Nasri F, Lui LMW, Siegel A, Mansur RB, Rosenblat JD, and McIntyre RS
- Subjects
- Adult, Child, Preschool, Depression, Humans, Quality of Life, Reward, Loneliness, Mental Disorders
- Abstract
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 system (including symptom and treatment aspects). Early childhood (distal) factors were found to be important in influencing adult (proximal) factors, which lead to the formulation of the construct. Due to the heterogenous and comorbid nature of depression, a new subtype known as 'reward depression' was distinguished along with distinct symptoms to aid practitioners when assessing patient treatment options. Furthermore, an evolutionary perspective was applied to the current impaired reward construct to discuss how the ancestral purpose and environment (in terms of reward) clashes with the modern one. Finally, theoretical treatment and prevention ideas were examined and discussed, leading into future work that needs to build upon and confirm the outlined construct., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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23. Insulin resistance is associated with deficits in hedonic, self-reported cognitive, and psychosocial functional response to antidepressant treatment in individuals with major depressive disorder.
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Rashidian H, Subramaniapillai M, Park C, Lipsitz O, Zuckerman H, Teopiz K, Cao B, Lee Y, Gill H, Ho R, Lin K, Rodrigues NB, Iacobucci M, Rosenblat JD, McIntyre RS, and Mansur RB
- Subjects
- Adult, Antidepressive Agents therapeutic use, Cognition, Double-Blind Method, Humans, Self Report, Depressive Disorder, Major drug therapy, Insulin Resistance
- Abstract
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. Response to vortioxetine was measured using the THINC-integrated tool, Montgomery Åsberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Perceived Deficits Questionnaire (PDQ-5), and the Sheehan Disability Scale (SDS). Generalized estimating equation models were utilized for data analysis., Results: When adjusted for age, gender, dose, and BMI, there was a significant baseline IR by time interaction for SHAPS (p = 0.022), PDQ-5 (p = 0.037), and SDS (p = 0.013). Higher baseline IR predicted decreased early improvements in anhedonia. It also predicted poorer subjective assessments of cognition and increased functional impairment at the endpoint of treatment. For functional capacity (i.e. SDS) other covariates including severity of symptoms, illness course, other metabolic factors (e.g. cholesterol), and physical activity were included with no changes to the moderating effect of baseline IR., Limitations: This was a post-hoc analysis of a primarily non-diabetic sample. Also, only one agent was assessed., Conclusions: IR was a predictor of response to vortioxetine. This persisted after controlling for other factors including, but not limited to, BMI. These findings strengthen the link between depression and IR and may point to another novel metabolic predictor of response. These findings should be replicated using other antidepressants., (Copyright © 2020. Published by Elsevier B.V.)
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- 2021
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24. A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions.
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Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Cha DS, Shekotikhina M, Vinberg M, Gill H, Subramaniapillai M, Kratiuk K, Lin K, Ho R, Mansur RB, and Rosenblat JD
- Subjects
- Dissociative Disorders chemically induced, Dissociative Disorders diagnosis, Dissociative Disorders drug therapy, Humans, Infusions, Intravenous, Retrospective Studies, Anesthetics therapeutic use, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine adverse effects
- Abstract
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 treatment-resistant depression (TRD) receiving IV ketamine were randomly divided into two datasets. The first dataset (n = 130) was leveraged to develop a brief 6-item version of the CADSS (CADSS-6) based on items most sensitive to ketamine-induced dissociation. The CADSS-6 questions were then applied to the second dataset (n = 130) and the Spearman's correlation between the full-length CADSS and the CADSS-6 were assessed., Results: The CADSS-6 was developed from questions 1, 2, 6, 7, 15, and 22 from the full length CADSS. There was a strong significant correlation between the CADSS-6 total score and the CADSS total score at infusions 1 (rs(106) = 0.92, p < 0.001), 2 (rs(100) = 0.91, p < 0.001), 3(rs(99) = 0.95, p < 0.001) and 4 (rs(102) = 0.94, p < 0.001)., Limitations: The CADSS-6 was developed using a retrospective data; therefore, the scale remains unvalidated in this population., Conclusions: The CADSS-6 presented herein was sensitive to dissociation experienced by patients receiving IV ketamine. Overall, the CADSS-6 was strongly correlated at each infusion with the full-length CADSS. While future studies should look to validate the CADSS-6 in a TRD sample, this scale offers clinicians a brief assessment that can be used to characterize symptoms of dissociation., (Copyright © 2020. Published by Elsevier B.V.)
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- 2021
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25. Effects of infliximab on brain neurochemistry of adults with bipolar depression.
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Mansur RB, Subramaniapillai M, Lee Y, Pan Z, Carmona NE, Shekotikhina M, Iacobucci M, Rodrigues N, Nasri F, Rosenblat JD, Brietzke E, Cosgrove VE, Kramer NE, Suppes T, Newport J, Hajek T, and McIntyre RS
- Subjects
- Adult, Aspartic Acid, Brain diagnostic imaging, Glutamic Acid, Humans, Infliximab therapeutic use, Prefrontal Cortex, Proton Magnetic Resonance Spectroscopy, Bipolar Disorder drug therapy, Neurochemistry
- Abstract
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, placebo-controlled trial with infliximab for adults with bipolar depression. We assessed the effects of infliximab on concentration of metabolites in the prefrontal cortex, using proton-magnetic resonance spectroscopy (
1 H-MRS), as well as its association with clinical outcomes (i.e. depressive symptom severity and cognitive function)., Results: Eighteen participants in the placebo and 15 in the infliximab group were included in this analysis. In the pre-specified primary outcome, there were no significant effects of treatment on prefrontal concentrations of N-acetylaspartate (NAA; p = 0.712). In the secondary analyses, there was a significant treatment by time interaction for glutamate (Glx; p = 0.018), indicating that Glx levels decreased in infliximab-treated patients, relative to placebo. Treatment group significantly moderated the association between changes in Glx levels and changes in a neurocognitive test (i.e. Digit Symbol Substitution Test; p = 0.014), indicating that in infliximab-treated participants reductions in Glx were associated with cognitive improvement., Conclusions: Treatment with infliximab did not affect prefrontal NAA concentration in adults with BD. Exploratory analysis suggested a potential effect of treatment on the glutamate system, a finding that should be confirmed and validated by additional studies., (Copyright © 2020. Published by Elsevier B.V.)- Published
- 2021
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26. The Effect of Loneliness on Distinct Health Outcomes: A Comprehensive Review and Meta-Analysis.
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Park C, Majeed A, Gill H, Tamura J, Ho RC, Mansur RB, Nasri F, Lee Y, Rosenblat JD, Wong E, and McIntyre RS
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- Anxiety diagnosis, Anxiety psychology, Cognition physiology, Depression diagnosis, Depression psychology, Female, Humans, Male, Health Status, Loneliness psychology, Mental Health trends, Quality of Life psychology
- Abstract
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 analyzed to examine for associations between loneliness (as measured by the UCLA Loneliness or de Jong Gierveld Loneliness Scales) and one or more health outcome(s). Health outcomes were broadly defined to include measures of mental health (i.e., depression, anxiety, suicidality, general mental health), general health (i.e., overall self-rated health), well-being (i.e., quality of life, life satisfaction), physical health (i.e., functional disability), sleep, and cognition. Loneliness had medium to large effects on all health outcomes, with the largest effects on mental health and overall well-being; however, this result may have been confounded by the breadth of studies exploring the association between loneliness and mental health, as opposed to other health outcomes. A significant effect of gender on the association between loneliness and cognition (i.e., more pronounced in studies with a greater proportion of males) was also observed. The adequate training of health care providers to perceive and respond to loneliness among patients should be prioritized., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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27. Changes in symptoms of anhedonia in adults with major depressive or bipolar disorder receiving IV ketamine: Results from the Canadian Rapid Treatment Center of Excellence.
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Rodrigues NB, McIntyre RS, Lipsitz O, Cha DS, Lee Y, Gill H, Majeed A, Phan L, Nasri F, Ho R, Lin K, Subramaniapillai M, Kratiuk K, Mansur RB, and Rosenblat JD
- Subjects
- Adult, Anhedonia, Canada, Humans, Retrospective Studies, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Ketamine
- Abstract
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 of age) patients receiving four infusions of intravenous (IV) ketamine at a community-based clinic. The primary outcome measure was change in anhedonia severity, as measured by the Snaith-Hamilton Pleasure Scale (SHAPS). Secondary measures sought to determine if improvement on the SHAPS mediated the effect of repeated IV ketamine infusions on symptoms of depression and suicidal ideations, as measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR
16 ) and anxiety, as measured using the Generalized Anxiety Disorder-7 (GAD-7)., Results: After adjusting for age, sex, primary diagnosis, concomitant medication, body mass index, and baseline depression severity, there was a statistically significant reduction in symptoms of anhedonia with IV ketamine treatment (F (2, 235.6) = 31.6, p < 0.001). Improvements in depressive symptoms, suicidal ideation, and anxiety symptoms with repeated-dose IV ketamine were significantly partially mediated by reduction in anhedonic severity. Moreover, the combination of number of infusions received and change in anhedonic severity accounted for 26% of the variance in depressive score improvements., Limitations: This is a post-hoc analysis of retrospective data and lacks a control group., Conclusion: Ketamine was effective in improving measures of anhedonia in this large, well-characterized community-based sample of adults with TRD. Improvements in anhedonia also partially mediated the significant improvement in depressive symptoms, suicidality, and anxiety., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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28. The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis.
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McIntyre RS, Carvalho IP, Lui LMW, Majeed A, Masand PS, Gill H, Rodrigues NB, Lipsitz O, Coles AC, Lee Y, Tamura JK, Iacobucci M, Phan L, Nasri F, Singhal N, Wong ER, Subramaniapillai M, Mansur R, Ho R, Lam RW, and Rosenblat JD
- Subjects
- Adult, Antidepressive Agents therapeutic use, Humans, Mood Disorders drug therapy, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
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 delivery was compared at discrete time-points (i.e., 24 h, 2-6 days, 7-20 days, 21-28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine., Results: The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591-1.903, p < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p = 0.139). At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499-1.538, p < 0.01). At 21-28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368-0.898, p < 0.01)., Limitations: Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery., Conclusions: The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD., (Copyright © 2020. Published by Elsevier B.V.)
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- 2020
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29. The utility of smartphone-based, ecological momentary assessment for depressive symptoms.
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Yim SJ, Lui LMW, Lee Y, Rosenblat JD, Ragguett RM, Park C, Subramaniapillai M, Cao B, Zhou A, Rong C, Lin K, Ho RC, Coles AS, Majeed A, Wong ER, Phan L, Nasri F, and McIntyre RS
- Subjects
- Depression, Ecological Momentary Assessment, Humans, Smartphone, Depressive Disorder, Major diagnosis, Depressive Disorder, Major therapy, Text Messaging
- Abstract
Background: Major Depressive Disorder (MDD) is a common and debilitating mood disorder. Individuals with MDD are often misdiagnosed or diagnosed in an untimely manner, exacerbating existing functional impairments. Ecological momentary assessment (EMA) involves the repeated sampling of an individual's symptoms within their natural environment and has been demonstrated to assist in illness assessment and characterization. Capturing data in this way would set the stage for improved treatment outcomes and serve as a complementary resource in the management and treatment of depressive symptoms., Methods: Online databases PubMed/MedLine and PsycINFO were searched using PRISMA guidelines and combinations of the following keywords: EMA, depression, smartphone app, diagnosing, symptoms, phone, app, ecological momentary assessment, momentary assessment, data mining, unobtrusive, passive data, GPS, sensor., Results: A total of nineteen original articles were identified using our search parameters and ten articles met the inclusion criteria for full-text review. Among the ten relevant studies, three studies evaluated feasibility, seven evaluated detection, and three evaluated treatment of MDD., Limitations: Limitations include that the design of all of the studies included in this review are non-randomized. It should be noted that most of the studies included were pilot studies and/or exploratory trials lacking a control group., Conclusions: Available evidence suggests that the use of passive smartphone-based applications may lead to improved management of depressive symptoms. This review aids the creation of new EMA applications, highlights the potential of EMA usage in clinical settings and drug development, emphasizes the importance for regulation of applications in the mental health field, and provides insight into future directions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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30. Corrigendum to "Applications of machine learning algorithms to predict therapeutic outcomes in depression: A meta-analysis and systematic review." J Affect Disord. 241 (2018) 519-532.
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Lee Y, Ragguett RM, Mansur RB, Boutilier JJ, Rosenblat JD, Trevizol A, Brietzke E, Lin K, Pan Z, Subramaniapillai M, Chan TCY, Fus D, Park C, Musial N, Zuckerman H, Chen VC, Ho R, Rong C, and McIntyre RS
- Abstract
The authors regret an error in one of the extracted data points in the meta-analysis. The classification accuracy for Serretti et al. (2007) was corrected to 64% (Table 3b). The overall results before and after this correction remain directionally consistent and are summarized below (Figures 2 and 3; Table 2; results subsection 3.6). The authors apologise for any inconvenience caused., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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31. The effectiveness of repeated intravenous ketamine on depressive symptoms, suicidal ideation and functional disability in adults with major depressive disorder and bipolar disorder: Results from the Canadian Rapid Treatment Center of Excellence.
- Author
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McIntyre RS, Rodrigues NB, Lee Y, Lipsitz O, Subramaniapillai M, Gill H, Nasri F, Majeed A, Lui LMW, Senyk O, Phan L, Carvalho IP, Siegel A, Mansur RB, Brietzke E, Kratiuk K, Arekapudi AK, Abrishami A, Chau EH, Szpejda W, and Rosenblat JD
- Subjects
- Adult, Canada, Depression, Humans, Infusions, Intravenous, Psychiatric Status Rating Scales, Retrospective Studies, Suicidal Ideation, Bipolar Disorder drug therapy, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy, Ketamine therapeutic use
- Abstract
Background: The effectiveness, tolerability, and safety of intravenous (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 a Canadian outpatient IV ketamine clinic., Methods: Adults (N = 213; M
age = 45) with Major Depressive Disorder or Bipolar Disorder, with a minimum of Stage 2 antidepressant resistance, received IV ketamine at a community-based multi-disciplinary clinic. The primary outcome measure was change from baseline to post-infusion 4 on the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR16 ; n = 190). Secondary measures included QIDS-SR16 -measured response and remission rates, changes from baseline to endpoint in Generalized Anxiety Disorder-7 Scale (GAD-7; n = 188) and the Sheehan Disability Scale (SDS; n = 168)., Results: Significant improvement in total depressive symptoms severity (p < 0.0001) was observed after four infusions of IV ketamine 0.5-0.75 mg/kg. Moreover, the response rate (QIDS-SR16 total score change ≥ 50%) was 27% and remission (QIDS-SR16 total score ≤5) rate was 13%. Patients receiving IV ketamine exhibited anxiolytic effects (p < 0.0001,), improved overall psychosocial function (p < 0.0001), and reduced suicidal ideation (p < 0.0001). Compared to the baseline infusion, dissociation severity significantly reduced in subsequent infusions., Limitations: This was a naturalistic, retrospective study, without a control group., Conclusions: IV ketamine was safe, well-tolerated, and effective at improving depressive, anxiety, and functional impairment symptoms in a well-characterized cohort of adults with TRD., Competing Interests: Declaration of Competing Interest Roger S. McIntyre is a consultant to speak on behalf of, and/or has received research support from Alkermes, Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Stanley Medical Research Institute, and CIHR/GACD/Chinese National Natural Research Foundation. Joshua D. Rosenblat has received research grant support from the Canadian Cancer Society, Canadian Psychiatric Association, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from Allergan, Lundbeck and COMPASS. JDR is the medical director of a private clinic providing intravenous ketamine infusions and intranasal esketamine for depression., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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32. Projected increases in suicide in Canada as a consequence of COVID-19.
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McIntyre RS and Lee Y
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- Adult, Betacoronavirus, COVID-19, Canada epidemiology, Coronavirus Infections economics, Coronavirus Infections virology, Female, Forecasting, Humans, Male, Mental Disorders virology, Middle Aged, Pandemics economics, Pneumonia, Viral economics, Pneumonia, Viral virology, SARS-CoV-2, Social Support, Suicide economics, Unemployment psychology, Coronavirus Infections psychology, Economic Recession statistics & numerical data, Mental Disorders epidemiology, Pneumonia, Viral psychology, Suicide statistics & numerical data, Unemployment statistics & numerical data
- Abstract
Macroeconomic indicators, notably unemployment, are significant moderators of suicide. We projected the number of excess suicides in Canada as a consequence of the impact of COVID-19 on unemployment. Annual suicide mortality (2000-2018) and unemployment (2000-2019) data were derived from Statistics Canada. Time-trend regression models were used to evaluate and predict the number of excess suicides in 2020 and 2021 for two possible projection scenarios following the COVID-19 pandemic: 1) an increase in unemployment of 1.6% in 2020, 1.2% in 2021, or 2) an increase in unemployment of 10.7% in 2020, 8.9% in 2021. A percentage point increase in unemployment was associated with a 1.0% increase in suicide between 2000 and 2018. In the first scenario, the rise in unemployment rates resulted in a projected total of 418 excess suicides in 2020-2021 (suicide rate per 100,000: 11.6 in 2020). In the second scenario, the projected suicide rates per 100,000 increased to 14.0 in 2020 and 13.6 in 2021, resulting in 2114 excess suicides in 2020-2021. These results indicate that suicide prevention in the context of COVID-19-related unemployment is a critical priority. Furthermore, timely access to mental healthcare, financial provisions and social/labour support programs, as well as optimal treatment for mental disorders is urgently needed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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33. Association of history of adverse childhood experiences with irritable bowel syndrome (IBS) in individuals with mood disorders.
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Rosenblat JD, Mansur RB, Brietzke E, Kennedy SH, Carvalho AF, Lee Y, Subramaniapillai M, Muzina DJ, Dale R, Tamura JK, Lui LMW, Park C, Phan L, Tuineag RM, and McIntyre RS
- Subjects
- Adult, Bipolar Disorder diagnosis, Bipolar Disorder psychology, Child, Cross-Sectional Studies, Depressive Disorder, Major diagnosis, Depressive Disorder, Major psychology, Female, Humans, Male, Middle Aged, Prevalence, Retrospective Studies, Sex Offenses psychology, Sex Offenses trends, Adverse Childhood Experiences trends, Irritable Bowel Syndrome diagnosis, Irritable Bowel Syndrome psychology, Mood Disorders diagnosis, Mood Disorders psychology
- Abstract
The objective of the current study was to assess the association between adverse childhood experiences (ACEs) 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 major depressive disorder (MDD; n = 279) or bipolar disorder (BD; n = 219). Data was sub-grouped and compared based on history of ACEs. In total, 69 of the 498 participants reported a diagnosis of IBS (13.8%). BD was associated with significantly elevated rates of IBS compared to MDD (18.5% versus 10.1% respectively). After adjusting for age and sex, history of childhood sexual abuse was associated with increased rates of IBS in mood disorder participants [adjusted odds ratio (aOR) = 1.95]. In the MDD subgroup, ACEs (all categories and individual categories) were not associated with increased rates of IBS. In the BD subgroup, history of childhood sexual abuse was associated with significantly increased rates of IBS (38% versus 14%; aOR = 3.7). In summary, BD was associated with a higher prevalence of IBS compared to MDD. Additionally, history of sexual abuse was associated with an increased prevalence of IBS in BD, but not in MDD., (Copyright © 2020. Published by Elsevier B.V.)
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- 2020
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34. Using early changes in cold cognition to predict response to vortioxetine in major depressive disorder.
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Park C, Zuckerman H, Subramaniapillai M, Mansur RB, Rosenblat JD, Cao B, Iacobucci M, Lee Y, Levitan R, Blumberger DM, and McIntyre RS
- Subjects
- Adult, Antidepressive Agents pharmacology, Cognition physiology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction drug therapy, Cognitive Dysfunction epidemiology, Depressive Disorder, Major epidemiology, Female, Humans, Male, Middle Aged, Ontario epidemiology, Predictive Value of Tests, Treatment Outcome, Vortioxetine pharmacology, Antidepressive Agents therapeutic use, Cognition drug effects, Depressive Disorder, Major diagnosis, Depressive Disorder, Major drug therapy, Vortioxetine therapeutic use
- Abstract
Antidepressant pharmacotherapy dominates current treatment in psychiatry, including treatment for major depressive disorder (MDD). However, the current trial-and-error process of medication selection contributes to treatment failure and unnecessarily exposes patients to lengthy and insufficient treatment trials. Notably, improvements in measures of cognition have been demonstrated to occur early during treatment and prior to improvements in clinical state. Cognitions have been categorized based on emotional valence (i.e., cold versus hot cognitions). Cold cognitions describe cognitive operations that are relevant to the processing of non-emotional information. The current analysis investigates whether early changes in cold cognition can predict response after 8 weeks of vortioxetine treatment in adults with MDD. This was secondary analysis of an 8-week, open-label study. Cognition was assessed at week 0 and week 2 to measure early cognitive change. Depressive symptom severity was assessed at week 0 and week 8 to measure treatment response. Eighty-one subjects were analyzed using binomial logistic regression models. Early change in cognition was a non-significant predictor of response (p = 0.845, SE = 0.599, OR = 1.124), which may have resulted from high data variability. The overall predictive accuracy of the model was low (sensitivity = 37.5%, specificity = 89.8%, PPV = 70.6%, NPV = 68.8%). Future studies should include larger samples and stratify patients based on potentially moderating variables, such as baseline cognitive impairment and occupation. Stratification would likely produce more homogenous samples, reducing the amount of variability observed for early cognitive change., Competing Interests: Declaration of Competing Interest Roger S. McIntyre is a consultant to speak on behalf for, and/or has received research support from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Stanley Medical Research Institute, and CIHR/GACD/Chinese National Natural Research Foundation. All other authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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35. Are early increases in physical activity a behavioral marker for successful antidepressant treatment?
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Yun L, Fagan M, Subramaniapillai M, Lee Y, Park C, Mansur RB, McIntyre RS, and Faulkner GEJ
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- Adult, Depression psychology, Female, Humans, Linear Models, Male, Middle Aged, Self Report, Severity of Illness Index, Treatment Outcome, Antidepressive Agents therapeutic use, Depression drug therapy, Exercise psychology, Vortioxetine therapeutic use
- Abstract
Background: The aim of this study was to examine whether changes in physical activity predicted reductions in depression during the 8 weeks of antidepressant treatment with vortioxetine., Methods: One hundred individuals were recruited for the (THINC-it ®)-sensitivity to change study. Self-reported moderate-to-vigorous physical activity (MVPA) and depression severity were assessed at baseline, week 4 and week 8. Linear mixed model analyses were performed to examine whether increases in MVPA were associated with reduction in depression severity over the course of treatment and hierarchical logistic regression analyses were performed to assess whether treatment response (responders vs. non-responders) at week 8 was predicted by early change in physical activity (MVPA at week 4), after controlling for individuals' demographics (sex, age, race, education level, BMI) and baseline MVPA and depression severity., Results: After controlling for individuals' demographics, a significant increase in MVPA predicted reduction in depression severity, β = -2.06, 95% CI -3.18, -0.94, p <0.001. Individuals with more physical activity at week 4 relative to baseline had higher odds of treatment response at endpoint, OR 1.97, 95% CI 1.11 - 3.48, p <0.05. Twenty-one percent of total variance of depression severity was explained by change in MVPA., Conclusions: The study suggests that early increases in physical activity may be a behavioral marker of antidepressant treatment response. The inclusion of physical activity measures in future clinical treatment trials of depression is recommended to explore whether changes in physical activity mediate or moderate reductions in depression severity associated with the primary treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2020
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36. Effort-based decision-making is affected by overweight/obesity in major depressive disorder.
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Mansur RB, Subramaniapillai M, Zuckerman H, Park C, Iacobucci M, Lee Y, Tuineag M, Hawco C, Frey BN, Rasgon N, Brietzke E, and McIntyre RS
- Subjects
- Adult, Body Mass Index, Depressive Disorder, Major complications, Depressive Disorder, Major physiopathology, Female, Humans, Male, Motivation, Obesity physiopathology, Anhedonia physiology, Decision Making physiology, Depressive Disorder, Major psychology, Obesity psychology, Reward
- Abstract
Background: Anhedonia and abnormalities in reward behavior are core features of major depressive disorder (MDD). Convergent evidence indicates that overweight/obesity (OW), a highly prevalent condition in MDD, is independently associated with reward disturbances. We therefore aimed to investigate the moderating effect of OW on the willingness to expend efforts for reward in individuals with MDD and healthy controls (HC)., Methods: Forty-one adults (HC n = 20, MDD n = 21) completed the Effort Expenditure for Rewards Task (EEfRT), clinical and cognitive measures. Anthropometric parameters were assessed in all participants, and an additional evaluation of laboratorial parameters were conducted solely on those with MDD. Individuals with MDD were all on vortioxetine monotherapy (10-20 mg/day)., Results: Interactions between reward magnitude, group and OW were observed (χ
2 = 9.192, p = 0.010); the OW-MDD group chose the hard task significantly less than normal weight (NW)-HC (p = 0.033) and OW-HC (p = 0.034), whereas there were no differences between NW-MDD and HCs. Within individuals with MDD, the proportion of hard task choices was more strongly correlated with body mass index (BMI) (r = -0.456, p = 0.043) and insulin resistance (HOMA2-IR) (r = -0.467, p = 0.038), than with depressive symptoms (r = 0.290, p = 0.214)., Conclusions: OW significantly moderated the association between MDD and willingness to make efforts for rewards. These findings offer novel evidence on the potential role of metabolic factors on the basis of anhedonia, and for the heuristic models proposing a pathophysiological connection between mood and metabolic disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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37. The neural systems of emotion regulation and abnormalities in major depressive disorder.
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Park C, Rosenblat JD, Lee Y, Pan Z, Cao B, Iacobucci M, and McIntyre RS
- Subjects
- Humans, Cerebral Cortex physiopathology, Depressive Disorder, Major physiopathology, Emotional Regulation physiology, Limbic System physiopathology, Nerve Net physiopathology
- Abstract
Major depressive disorder (MDD) is a mental disorder characterized by aberrant emotion regulation. The capacity for emotion regulation stems from diverse neural circuits including higher level cognitive structures involved in processing contextual information, and lower level limbic structures involved in triggering emotional expression. Cognitive theories of depression posit that the MDD-specific abnormalities in emotional control derive itself from dysfunctional cognitive processes including biased attention, rumination, and altered information processing and memory. The main objectives of the current narrative review are to summarize the major neural systems involved in emotion regulation in humans, and to describe how these systems are dysregulated in MDD. The findings will be briefly discussed in the context of a conceptual framework of depression (i.e., Beck's cognitive model of depression), and neural targets of conventional treatments for depression will also be discussed. MDD exemplifies the critical importance of appropriate emotion regulation to human health and wellbeing, and demonstrates the personal and social impact of emotion dysregulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2019
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38. The long-term effect of bariatric surgery on depression and anxiety.
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Gill H, Kang S, Lee Y, Rosenblat JD, Brietzke E, Zuckerman H, and McIntyre RS
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- Anxiety surgery, Depression surgery, Humans, Obesity, Morbid complications, Obesity, Morbid psychology, Psychiatric Status Rating Scales, Treatment Outcome, Anxiety etiology, Bariatric Surgery psychology, Depression etiology, Obesity, Morbid surgery
- Abstract
Background: No previous review has comprehensively assessed long-term changes in anxiety and depressive symptoms in bariatric surgery patients. This systematic review assessed the effects of bariatric surgery on long-term reductions (≥ 24 months) in anxiety and depressive symptom severity in morbidly obese (≥ 35 BMI kg/m
2 ) participants. Short term effects (< 24 months) are briefly reviewed for context., Methods: PsychINFO, Google Scholar and PubMed databases were systematically searched for prospective cohort studies published from inception to 14 June 2018 that evaluated long-term (≥ 24 months) changes in anxiety and depressive symptom severity in bariatric surgery patients with a BMI ≥ 35 kg/m2 using a combination of the following search terms: bariatric surgery (and surgical approaches included under this term), obesity, depression, depressive disorder, anxiety, anxious, psychiatric disorders, mood disorders., Results: We reviewed 2058 articles for eligibility; 14 prospective studies were included in the systematic review. 13 studies (93%) reported significant reductions in depressive symptom severity 2-3 years after bariatric surgery. However, all studies recorded statistically significant reductions in depressive symptoms at the conclusion of the study. Similarly, there were reductions in overall anxiety symptom severity at ≥ 24 months follow-up (k = 8 studies, n = 1590 pooled). Pre-operative anxiety or depression scores did not predict outcomes of post-operative BMI. Similarly, post-surgery weight loss did not predict changes in anxiety symptoms., Limitations: Very few studies assessed anxiety or depression as a primary outcome. Therefore, we cannot suggest bariatric surgery as a stand-alone therapeutic tool for anxiety and depression based on our findings., Conclusion: Currently available evidence suggests that bariatric surgery is associated with long-term reductions in anxiety and depressive symptoms. This supports existing literature showing that metabolic treatments may be a viable therapeutic intervention for mood disorders., (Copyright © 2018. Published by Elsevier B.V.)- Published
- 2019
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39. Hypersomnia and Bipolar Disorder: A systematic review and meta-analysis of proportion.
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Grigolon RB, Trevizol AP, Cerqueira RO, Lee Y, Mansur RB, McIntyre RS, and Brietzke E
- Subjects
- Bipolar Disorder diagnosis, Cross-Sectional Studies, Databases, Factual, Disorders of Excessive Somnolence diagnosis, Humans, Prevalence, Risk, Bipolar Disorder epidemiology, Disorders of Excessive Somnolence epidemiology
- Abstract
Background: Hypersomnia is a common problem amongst individuals with Bipolar Disorder (BD). The objective of this meta-analysis is to estimate the frequency of hypersomnia in individuals with BD, and identify associated factors METHODS: Our search focused on articles documenting the frequency of hypersomnia among individuals with BD indexed in PubMed database and in the Cochrane Library, following the recommendations from the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) Group. A meta-analysis of proportion was conducted; funnel plot and Egger's test were used for the assessment of publication bias. Subgroups analyses were performed in order to evaluate possible confounders and associated factors., Results: We identified 10 studies, which included 1824 patients with BD. The overall estimate of the proportion of BD cases that reported hypersomnia was 29.9% [95% confidence interval (CI): 25.8 - 34.1%, I
2 = 59.2%; p < .05]. The funnel plot and the Egger's test suggest a low risk of publication bias (p = .527). The polarity of mood state, Bipolar Disorder type, use of medication, age, diagnostic criteria and hypersomnia criteria were not significantly related to hypersomnia., Limitations: There is a possibility that smaller cross-sectional studies were not included. The high heterogeneity between studies is frequent in meta-analysis of both interventional and observational studies. Hypersomnia was not the primary outcome in some of the included studies., Conclusions: To our knowledge, this is the first systematic review and meta-analysis of hypersomnia prevalence in patients with BD. Further studies focused on clinical correlates and implications for health outcomes in BD are warranted., (Copyright © 2018. Published by Elsevier B.V.)- Published
- 2019
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40. The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: A meta-analysis.
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Rosenblat JD, Lee Y, and McIntyre RS
- Subjects
- Cohort Studies, Depressive Disorder, Major physiopathology, Humans, Odds Ratio, Pharmacogenetics, Treatment Outcome, Antidepressive Agents therapeutic use, Depressive Disorder, Major drug therapy, Pharmacogenomic Testing
- Abstract
Background: Pharmacogenomic testing has recently become scalable and available to guide the treatment of major depressive disorder (MDD). The objective of the current meta-analysis was to determine if guidance from pharmacogenomic testing results in relatively higher rates of remission and response compared to treatment as usual (i.e., 'unguided' trial-and-error method) in adults with MDD., Methods: Article databases were systematically searched from inception to December 2, 2017 for human studies assessing the clinical utility of pharmacogenomics in the acute treatment of MDD. Treatment outcomes in MDD may be defined continuously or categorically (i.e., response/remission). Herein, we delimit our focus on categorical outcomes. Using a random-effects model, data was pooled to determine the risk ratio (RR) of response and remission, respectively, in the pharmacogenomic-guided treatment group compared to the unguided group., Results: Four randomized controlled trials (RCTs) and two open-label, controlled cohort studies were included. The pooled RR for treatment response comparing guided versus unguided treatment was 1.36 (95% confidence interval [CI] = 1.14 to 1.62; p = 0.0006; n = 799) in favour of guided treatment. The pooled RR for remission was 1.74 (95%CI = 1.09 to 2.77; p = 0.02, n = 735) also in favour of guided treatment. Heterogeneity in study results suggest that different genetic tests may variably impact response and remission rates., Limitations: The available evidence is limited, with significant methodological deficiencies., Conclusion: The current analysis provides preliminary support for improved response and remission rates in MDD when treatment is guided by pharmacogenomics., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2018
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41. Applications of machine learning algorithms to predict therapeutic outcomes in depression: A meta-analysis and systematic review.
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Lee Y, Ragguett RM, Mansur RB, Boutilier JJ, Rosenblat JD, Trevizol A, Brietzke E, Lin K, Pan Z, Subramaniapillai M, Chan TCY, Fus D, Park C, Musial N, Zuckerman H, Chen VC, Ho R, Rong C, and McIntyre RS
- Subjects
- Adult, Depressive Disorder diagnosis, Female, Humans, Male, Neuroimaging, Retrospective Studies, Treatment Outcome, Algorithms, Antidepressive Agents therapeutic use, Depressive Disorder drug therapy, Diagnosis, Computer-Assisted, Machine Learning
- Abstract
Background: No previous study has comprehensively reviewed the application of machine learning algorithms in mood disorders populations. Herein, we qualitatively and quantitatively evaluate previous studies of machine learning-devised models that predict therapeutic outcomes in mood disorders populations., Methods: We searched Ovid MEDLINE/PubMed from inception to February 8, 2018 for relevant studies that included adults with bipolar or unipolar depression; assessed therapeutic outcomes with a pharmacological, neuromodulatory, or manual-based psychotherapeutic intervention for depression; applied a machine learning algorithm; and reported predictors of therapeutic response. A random-effects meta-analysis of proportions and meta-regression analyses were conducted., Results: We identified 639 records: 75 full-text publications were assessed for eligibility; 26 studies (n=17,499) and 20 studies (n=6325) were included in qualitative and quantitative review, respectively. Classification algorithms were able to predict therapeutic outcomes with an overall accuracy of 0.82 (95% confidence interval [CI] of [0.77, 0.87]). Pooled estimates of classification accuracy were significantly greater (p < 0.01) in models informed by multiple data types (e.g., composite of phenomenological patient features and neuroimaging or peripheral gene expression data; pooled proportion [95% CI] = 0.93[0.86, 0.97]) when compared to models with lower-dimension data types (pooledproportion=0.68[0.62,0.74]to0.85[0.81,0.88])., Limitations: Most studies were retrospective; differences in machine learning algorithms and their implementation (e.g., cross-validation, hyperparameter tuning); cannot infer importance of individual variables fed into learning algorithm., Conclusions: Machine learning algorithms provide a powerful conceptual and analytic framework capable of integrating multiple data types and sources. An integrative approach may more effectively model neurobiological components as functional modules of pathophysiology embedded within the complex, social dynamics that influence the phenomenology of mental disorders., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2018
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42. Predicting antidepressant response using early changes in cognition: A systematic review.
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Park C, Pan Z, Brietzke E, Subramaniapillai M, Rosenblat JD, Zuckerman H, Lee Y, Fus D, and McIntyre RS
- Subjects
- Cognitive Dysfunction diagnosis, Cognitive Dysfunction drug therapy, Depressive Disorder, Major psychology, Humans, Prognosis, Antidepressive Agents therapeutic use, Cognition drug effects, Depressive Disorder, Major diagnosis, Depressive Disorder, Major drug therapy
- Abstract
Background: Despite the widespread use of antidepressants in clinical practice, the current trial-and-error approach to medication selection contributes to treatment failure and underscores the need to identify reliable predictors of antidepressant response. Since changes in measures of cognition have been reported to occur early in treatment and prior to improvements in overall mood symptoms, the present review aims to determine whether early changes in measures of cognition can predict response in individuals with MDD., Methods: A systematic review of studies evaluating early cognitive change as a predictor of later treatment response in MDD was conducted using PubMed/Medline, Embase and PsychINFO., Results: A total of seven articles were identified. The available evidence suggests the early changes in cognition may predict treatment response in individuals with MDD. This was shown across antidepressant classes (i.e., SSRIs, SNRIs, NRIs, melatonergic antidepressants) and forms of therapy (i.e., pharmacotherapy, rTMS). The results depict an emerging trend towards early changes in facial emotion recognition (i.e., a hot cognitive process) as a predictor of treatment outcome., Limitations: Our qualitative analysis reflects a very limited number of studies. Moreover, there was significant heterogeneity in the evaluation of cognition across studies. Future research should aim to parse out this heterogeneity by evaluating the relative predictive value of different measures of cognition., Conclusion: The identification of reliable early treatment predictors of antidepressant response would be clinically significant, enabling clinicians to more accurately evaluate the efficacy of selected treatment avenues., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2018
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43. Cognitive impairment as measured by the THINC-integrated tool (THINC-it): The association with self-reported anxiety in Major Depressive Disorder.
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Cha DS, Carmona NE, Rodrigues NB, Mansur RB, Lee Y, Subramaniapillai M, Phan L, Cha RH, Pan Z, Lee JH, Lee J, Almatham F, Alageel A, Rosenblat JD, Shekotikhina M, Rong C, Harrison J, and McIntyre RS
- Subjects
- Adult, Aged, Anxiety psychology, Cross-Sectional Studies, Female, Humans, Male, Mass Screening, Middle Aged, Recurrence, Regression Analysis, Surveys and Questionnaires, Young Adult, Cognition, Cognitive Dysfunction psychology, Depressive Disorder, Major psychology, Self Report
- Abstract
Background and Objectives: This study evaluated the association between self-reported anxiety and objective/subjective measures of cognitive performance in adults with Major Depressive Disorder (MDD)., Methods: Acutely depressed subjects with recurrent MDD (n = 100) and age-, sex-, and education-matched healthy controls (HC; n = 100) between the ages of 18 and 65 completed the cross-sectional validation study of the THINC-integrated tool (THINC-it; ClinicalTrials.gov: NCT02508493). Objective cognitive performance was assessed using the THINC-it, and subjective cognitive impairment with the Perceived Deficits Questionnaire for Depression-5-item. Subjects also completed the Generalized Anxiety Disorder-7-item (GAD-7) questionnaire., Results: Subjects with MDD reported significantly more anxiety symptoms, as assessed by the GAD-7, compared to HC (p < 0.001). Linear regression analysis determined that anxiety symptoms significantly accounted for 70.4% of the variability in subjective cognitive impairment, adjusting for depression severity. Moreover, subjects' ratings of the difficulties caused by their anxiety were reported as significantly more severe among subjects with MDD when compared to HC (p < 0.001). Likewise, greater self-reported difficulties with anxiety significantly predicted 57.8% of the variability in subjective cognitive impairment, adjusting for depression severity. Neither anxiety symptoms nor impairment due to anxiety symptoms predicted objective cognitive performance., Limitations: Subjects were not prospectively verified to have a clinical diagnosis of GAD. Rather, this study examined the relationships between symptoms of generalized anxiety, assessed using a brief screening tool, and subjective and objective cognitive function., Conclusions: Results from the current study indicate that adults with MDD and high levels of self-reported anxiety are significantly more likely to report experiencing subjective cognitive dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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44. Efficacy of antidepressants on measures of workplace functioning in major depressive disorder: A systematic review.
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Lee Y, Rosenblat JD, Lee J, Carmona NE, Subramaniapillai M, Shekotikhina M, Mansur RB, Brietzke E, Lee JH, Ho RC, Yim SJ, and McIntyre RS
- Subjects
- Antidepressive Agents adverse effects, Cost of Illness, Cost-Benefit Analysis, Depressive Disorder, Major diagnosis, Depressive Disorder, Major economics, Depressive Disorder, Major psychology, Disability Evaluation, Double-Blind Method, Humans, Quality of Life, Randomized Controlled Trials as Topic, Workplace, Antidepressive Agents therapeutic use, Depressive Disorder, Major drug therapy, Work Performance
- Abstract
Introduction: Work-related disability and productivity loss in Major Depressive Disorder (MDD) are critical determinants of patient quality of life and contribute significantly to the human and economic costs of MDD. Notwithstanding the return to work and pre-morbid levels of functioning as a critical therapeutic objective among individuals with MDD, it is unclear whether antidepressant treatment significantly and reliably improves measures of workplace functioning. Herein, we investigate to what extent antidepressant treatment improves workplace functioning among adults with MDD., Methods: We conducted a systematic review of randomized, double-blind, placebo-controlled or active comparator clinical trials primarily or secondarily investigating the efficacy of antidepressant agents on subjective ratings of workplace functioning and/or measures of work absence., Results: Thirteen placebo-controlled and four active comparator clinical trials reported on the efficacy of agomelatine, bupropion, desvenlafaxine, duloxetine, fluoxetine, levomilnacipran, paroxetine, sertraline, venlafaxine, or vortioxetine on subjective measures of workplace impairment. Overall, antidepressant treatment improved standardized measures of workplace functioning (e.g., Sheehan Disability Scale-work item). One placebo-controlled trial of agomelatine and one clinical trial comparing the efficacy of vortioxetine to that of venlafaxine had mixed results on measures of work absence., Limitations: Included interventional trials evaluated work-related disability as a secondary outcome using subjective rating scales., Conclusion: Extant data suggest that antidepressant treatment improves workplace outcomes in MDD. The capability of antidepressants in improving measures of workplace functioning should be considered in cost-benefit analyses to better inform cost-modelling studies pertaining to antidepressant therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2018
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45. Correlation between brain circuit segregation and obesity.
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Chao SH, Liao YT, Chen VC, Li CJ, McIntyre RS, Lee Y, and Weng JC
- Subjects
- Adult, Body Mass Index, Brain diagnostic imaging, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Models, Neurological, Neural Pathways diagnostic imaging, Obesity diagnostic imaging, Statistics as Topic, Young Adult, Brain pathology, Brain Mapping, Neural Pathways physiology, Obesity pathology
- Abstract
Obesity is a major public health problem. Herein, we aim to identify the correlation between brain circuit segregation and obesity using multimodal functional magnetic resonance imaging (fMRI) techniques and analysis. Twenty obese patients (BMI=37.66±5.07) and 30 healthy controls (BMI=22.64±3.45) were compared using neuroimaging and assessed for symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). All participants underwent resting-state fMRI (rs-fMRI) and T1-weighted imaging using a 1.5T MRI. Multimodal MRI techniques and analyses were used to assess obese patients, including the functional connectivity (FC), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and voxel-based morphometry (VBM). Correlations between brain circuit segregation and obesity were also calculated. In the VBM, obese patients showed altered gray matter volumes in the amygdala, thalamus and putamen. In the FC, the obesity group showed increased functional connectivity in the bilateral anterior cingulate cortex and decreased functional connectivity in the frontal gyrus of default mode network. The obesity group also exhibited altered ALFF and ReHo in the prefrontal cortex and precuneus. In the GTA, the obese patients showed a significant decrease in local segregation and a significant increase in global integration, suggesting a shift toward randomization in their functional networks. Our results may provide additional evidence for potential structural and functional imaging markers for clinical diagnosis and future research, and they may improve our understanding of the underlying pathophysiology of obesity., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2018
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46. Risks of road injuries in patients with bipolar disorder and associations with drug treatments: A population-based matched cohort study.
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Chen VC, Yang YH, Lee CP, Wong J, Ponton L, Lee Y, McIntyre RS, Huang KY, and Wu SI
- Subjects
- Adult, Aged, Anticonvulsants therapeutic use, Cohort Studies, Comorbidity, Female, Humans, Incidence, International Classification of Diseases, Lithium therapeutic use, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, Research Design, Risk Factors, Accidents, Traffic statistics & numerical data, Antidepressive Agents therapeutic use, Antipsychotic Agents therapeutic use, Bipolar Disorder drug therapy
- Abstract
Objective: Using a nation-wide, population-based dataset, we aimed to investigate the risk of road injury among individuals with bipolar disorder (BD) compared to individuals without BD. In addition, we investigated the putative moderating effects of prescription for lithium, anticonvulsants, antidepressants, and/or first- or second-generation antipsychotic agents on the association between BD and risk of road injury., Method: As part of an16-year longitudinal cohort study, we compared the risk of road injuries among study subjects aged 16 and above with a diagnosis of BD, with ten age- and sex-matched sample of individuals without BD. Individuals were compared on measures of incidence on road injuries using medical claims data based on the ICD-9-CM codes: E800~807, E810~817, E819~830, E840~848. Time dependent Cox regression models were used to adjust for time-varying covariates such as age, and medication uses. Hazard ratios before and after adjusting for age, sex, other comorbidities, and drug use were calculated., Results: 3953 people with BD were matched with 39,530 controls from general population. Adjusted hazard ratios revealed a 1.66-fold (95% CI 1.40-1.97) increase in risk of road injuries among bipolar subjects when compared to controls. Female gender, older age (i.e. over 80), residence in areas of highest levels of urbanization, and use of antidepressants were associated with a lower risk of road injuries., Conclusions: In this large, national, population-based cohort, BD was associated with an elevated risk of road injuries. However, prescriptions of antidepressants might help mitigate the foregoing risk., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2018
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47. Cognitive impairment as measured by the THINC-integrated tool (THINC-it): Association with psychosocial function in major depressive disorder.
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Cha DS, Carmona NE, Subramaniapillai M, Mansur RB, Lee Y, Hon Lee J, Lee J, Rosenblat JD, Shekotikhina M, Park C, Rong C, Greer TL, Lam R, Baune BT, Harrison J, and McIntyre RS
- Subjects
- Adolescent, Adult, Aged, Cognition Disorders diagnosis, Cognitive Dysfunction psychology, Cross-Sectional Studies, Depression diagnosis, Depressive Disorder, Major psychology, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Self Report, Social Behavior, Cognitive Dysfunction diagnosis, Depressive Disorder, Major diagnosis
- Abstract
Background: Psychosocial impairment represents an important treatment target in major depressive disorder (MDD). The majority of patients with MDD do not regain premorbid levels of psychosocial functioning despite the resolution of core depressive symptoms. This study aimed to investigate the respective effects of cognitive function and depression severity on impaired psychosocial function in MDD., Methods: Adults aged 18-65 with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls participated in a cross-sectional study validating the THINC-integrated tool (THINC-it), a cognitive screening tool comprised of objective and subjective measures of cognitive function. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale and psychosocial function was assessed using the Sheehan Disability Scale (SDS)., Results: Subjects with MDD reported greater impairment in psychosocial function than healthy controls, with significant differences in SDS total and domain scores (ps < .01) after controlling for age, sex, and education. Generalized linear models indicated that subjective cognitive function was most strongly associated with SDS total score (RR = .14, p = .01) and SDS domains of work/school (RR = .15, p = .03), family and home responsibilities (RR = .15, p = .02), and economic days lost (RR = .18, p =.03). Depression severity was most strongly associated with SDS social life (RR = .08, p < .01) and economic days underproductive (RR = .07, p < .01). Objective cognitive function was not significantly associated with any SDS outcomes., Limitations: The cross-sectional, observational study design limits temporal inferences. The self-report nature of measures included may have influenced associations observed. Potential medication effects are not noted., Conclusions: Cognitive deficits, as measured by the THINC-it, are associated with significant psychosocial impairment in MDD. These results provide empirical support for the assessment of both subjective and objective measures of cognition, as they are not associated with each other and have differential effects on functional trajectory., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2017
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48. Factors affecting lumbar surgery outcome: A nation-wide, population-based retrospective study.
- Author
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Chin-Hung Chen V, Yang YH, Chen PY, Yang JT, Chen CPC, Chen CJ, Lu ML, Lee Y, McIntyre RS, and Huang YC
- Subjects
- Adult, Aged, Anxiety complications, Asthma complications, Comorbidity, Female, Humans, Longitudinal Studies, Low Back Pain complications, Male, Middle Aged, Multivariate Analysis, Pain Management psychology, Retrospective Studies, Taiwan, Treatment Outcome, Low Back Pain surgery, Lumbar Vertebrae surgery, Postoperative Complications etiology
- Abstract
Background: Lower back pain is a very common symptom and treatment strategies vary according the severity and duration of illness. Surgical approaches are becoming increasingly popular with the advent of new and less invasive technologies; however, treatment outcomes are not yet well established on a population-based level. Taiwan's National Health Insurance Research Database (NHIRD) is longitudinal and includes 98% of the population since its inception in 1995. The database includes the ICD 9.0 codes (International Classification of Diseases) of all patients with lower back pain and lumbar surgery; furthermore, all the prescriptions., Methods: As part of a population-based cohort study of one million participants randomly selected from the NHIRD, we analyzed changes in prescription of analgesics 1 year before and 1 year after lumbar surgery; comorbidities, such as diabetes, asthma, osteoporosis, arthritis, depression and anxiety were also analyzed as covariates. A total of 3916 cases were enrolled in final analysis., Results: Post-operatively, the defined daily dosage (DDD) of analgesics decreased from a median DDD of 50.0 to a median of 14.2. In a multivariate model analysis, female, older age, anxiety and asthma were the significant factors for unfavorable outcome (defined by dosage of analgesics decreased less than 50% after surgery)., Conclusions: The analgesics significantly decreased for patients received lumbar surgeries, implying the decreased of pain. In addition, co-morbidity factors were identified by the failure for analgesics reduction, such as female, older age, anxiety and asthma. For patients with lower back pain, these factors should be considered before receiving lumbar surgeries., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2017
- Full Text
- View/download PDF
49. Bipolar disorder and the risk of fracture: A nationwide population-based cohort study.
- Author
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Su JA, Cheng BH, Huang YC, Lee CP, Yang YH, Lu ML, Hsu CY, Lee Y, McIntyre RS, Chin Lin T, and Chin-Hung Chen V
- Subjects
- Adult, Antimanic Agents therapeutic use, Bipolar Disorder drug therapy, Case-Control Studies, Female, Humans, Lithium Compounds therapeutic use, Male, Middle Aged, Proportional Hazards Models, Retrospective Studies, Risk Factors, Taiwan, Anticonvulsants therapeutic use, Antipsychotic Agents therapeutic use, Bipolar Disorder complications, Fractures, Bone psychology, Insurance, Health statistics & numerical data
- Abstract
Background: The co-primary aims are: 1) to compare the risk of fracture between adults with bipolar disorder and those without bipolar disorder; and 2) to assess whether lithium, anticonvulsants and antipsychotics reduce risk of fracture among individuals with bipolar disorder., Methods: The analysis herein is a population-based retrospective cohort study, utilizing the National Health Insurance (NHI) medical claims data collected between 1997 and 2013 in Taiwan. We identified 3705 cases with incident diagnoses of bipolar disorder during study period and 37,050 matched controls without bipolar diagnoses. Incident diagnosis of fracture was operationalized as any bone fracture after the diagnosis of bipolar disorder or after the matched index date for controls., Results: Bipolar patients had significantly higher risk of facture when compared to matched controls (17.6% versus 11.7%, respectively p<0.001). The hazard ratio (HR) was 1.33 (95% confidence interval [CI]=1.23-1.48, p<0.001) after adjusting for covariates. Persons with bipolar disorder and a prior history of psychiatric hospitalization were had higher risk for bone fracture than those without prior history of psychiatric hospitalization when compared to match controls. Higher cumulative dose of antipsychotics or mood stabilizers did not increase the risk of fracture., Limitations: The diagnoses of bipolar disorder were not confirmed with structured clinical interview. Drug adherence, exact exposure dosage, smoking, lifestyle, nutrition and exercise habits were unable to be assessed in our dataset., Conclusions: Bipolar disorder is associated with increased risk of fracture, and higher cumulative dose of mood stabilizers and antipsychotics did not further increase the risk of fracture., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2017
- Full Text
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50. The association between insulin resistance and depression in the Korean general population.
- Author
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Lee JH, Park SK, Ryoo JH, Oh CM, Mansur RB, Alfonsi JE, Cha DS, Lee Y, McIntyre RS, and Jung JY
- Subjects
- Adult, Cross-Sectional Studies, Depression epidemiology, Diabetes Complications, Female, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Republic of Korea epidemiology, Socioeconomic Factors, Depression complications, Insulin Resistance
- Abstract
Background: Previous studies showed that the insulin resistance (IR) could be related to depression. However, this association is still equivocal in the general population. Herein, we aimed to investigate the association between IR and depressive symptoms in a large sample in South Korea., Methods: A cross-sectional study was carried out for 165,443 Korean men and women who received a health checkup including various clinical parameters and the Center for Epidemiologic Studies Depression scales (CES-D). Subjects were stratified into subgroups by CES-D score, sex, age, and presence of diabetes. The odd ratios (ORs) for homeostasis model assessment of insulin resistance (HOMA-IR) were compared between groups using multivariable logistic regression analyses., Results: After adjusting covariates (e.g. smoking, family income, marriage state, unemployment status, average alcohol use, BMI, physical activity, systolic blood pressure, diabetes), increased IR was weakly associated with greater depressive symptoms (adjusted OR=1.01 [95% CI 1.0001-1.03]). Subgroup analysis revealed this association was statistically significant in females (adjusted OR=1.03, [95% CI 1.001-1.06]), non-diabetic group (adjusted OR=1.04, [95% CI 1.02-1.06]), and young participants under the age of thirty (adjusted OR=1.17, [95% CI 1.07-1.27]). But we couldn't find significant association in diabetic and middle to elderly participants., Conclusions: This study demonstrates that there is a relationship between IR and depressive symptoms in the Korean general population. Results from this epidemiological study revealed that young adults and non-diabetic individuals with increased IR may be related with depressive symptoms., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
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