49 results on '"Rosenblat, Joshua D"'
Search Results
2. Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine
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Kwan, Angela T.H., Le, Gia Han, Guo, Ziji, Ceban, Felicia, Teopiz, Kayla M., Rhee, Taeho Greg, Ho, Roger, Di Vincenzo, Joshua D., Badulescu, Sebastian, Meshkat, Shakila, Cao, Bing, Rosenblat, Joshua D., Dev, Donovan A., Phan, Lee, Subramaniapillai, Mehala, and McIntyre, Roger S.
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- 2024
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3. Depression, anxiety and post-traumatic stress during the 2022 Russo-Ukrainian war, a comparison between populations in Poland, Ukraine, and Taiwan
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Chudzicka-Czupała, Agata, Hapon, Nadiya, Chiang, Soon-Kiat, Żywiołek-Szeja, Marta, Karamushka, Liudmyla, Lee, Charlotte T., Grabowski, Damian, Paliga, Mateusz, Rosenblat, Joshua D., Ho, Roger, McIntyre, Roger S., and Chen, Yi-Lung
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- 2023
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4. Peripheral inflammatory biomarkers define biotypes of bipolar depression
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Lee, Yena, Mansur, Rodrigo B, Brietzke, Elisa, Kapogiannis, Dimitrios, Delgado-Peraza, Francheska, Boutilier, Justin J, Chan, Timothy CY, Carmona, Nicole E, Rosenblat, Joshua D, Lee, JungGoo, Maletic, Vladimir, Vinberg, Maj, Suppes, Trisha, Goldstein, Benjamin I, Ravindran, Arun V, Taylor, Valerie H, Chawla, Sahil, Nogueras-Ortiz, Carlos, Cosgrove, Victoria E, Kramer, Nicole E, Ho, Roger, Raison, Charles A, and McIntyre, Roger S
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Brain Disorders ,Clinical Research ,Neurosciences ,Depression ,Mental Health ,Biomarkers ,Bipolar Disorder ,Humans ,Infliximab ,Insulin Receptor Substrate Proteins ,MAP Kinase Signaling System ,NF-kappa B ,Tumor Necrosis Factor-alpha ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.
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- 2021
5. Development and implementation of guidelines for the management of depression: a systematic review/Developpement et mise en reuvre des directives pour la gestion de la depression: revue systematique/Elaboracion e implementacion de directrices para el tratamiento de la depresion: una revision sistematica
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Lee, Yena, Brietzke, Elisa, Cao, Bing, Chen, Yan, Linnaranta, Outi, Mansur, Rodrigo B., Cortes, Paulina, Kosters, Markus, Majeed, Amna, Tamura, Jocelyn K., Lui, Leanna M.W., Vinberg, Maj, Keinanen, Jaakko, Kisely, Steve, Naveed, Sadiq, Barbui, Corrado, Parker, Gary, Owolabi, Mayowa, Nishi, Daisuke, Lee, JungGoo, Srisurapanont, Manit, Gill, Hartej, Guo, Lan, Balanza-Martinez, Vicent, Partonen, Timo, Nolen, Willem A., Lee, Jae-Hon, Kim, Ji Hwan, Chavannes, Niels H., Ewais, Tatjana, Atienza-Carbonell, Beatriz, Silven, Anna V., Yasuma, Naonori, Gil, Artyom, Novikov, Andrey, Lacey, Cameron, Versluis, Anke, von Malortie, Sofia, Chan, Lai Fong, Waqas, Ahmed, Purgato, Marianna, Aardoom, Jiska Joelle, Ly-Uson, Josefina T., Sim, Kang, Tuineag, Maria, van der Kleij, Rianne M.J.J., van Luenen, Sanne, Suttajit, Sirijit, Hajek, Tomas, Lee, Yu Wei, Porter, Richard J., Alsuwaidan, Mohammad, Rosenblat, Joshua D., Ravindran, Arun V., Lam, Raymond W., and McIntyre, Roger S.
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Singapore. Ministry of Health ,Depression (Mood disorder) -- Comparative analysis ,Bipolar disorder -- Comparative analysis ,Health ,World Health Organization - Abstract
Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. Findings We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. Conclusion Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes. [phrase omitted] [phrase omitted] Objectif Evaluer le developpement et la mise en reuvre des directives de pratique clinique pour la gestion de la depression dans le monde. Methodes Nous avons effectue une revue systematique des directives existantes en matiere de gestion de la depression chez les adultes souffrant de troubles depressifs majeurs ou de troubles bipolaires. Pour chaque directive identifiee, nous avons verifie le degre de conformite vis-a-vis des mesures de qualite du developpement des directives (transparence des processus d'elaboration des directives et de leur financement, composition multidisciplinaire du groupe d'auteurs, revue systematique des etudes d'efficacite comparative) ainsi que de la mise en reuvre (indicateurs de qualite). Nous avons confronte les directives des pays a faible et moyen revenu avec celles des pays a haut revenu. Resultats Nous avons identifie 82 directives de pratique clinique nationales et 13 directives de pratique clinique internationales dans 83 pays et en 27 langues. Les processus d'elaboration des directives et les sources de financement etaient explicitement indiquees dans une moindre proportion chez les pays a faible et moyen revenu (8/29; 28%) par rapport aux pays a haut revenu (35/58; 60%). Le nombre de directives redigees par un groupe d'auteurs multidisciplinaire etait moins eleve dans les pays a faible et moyen revenu (2/29; 7%) que dans les pays a haut revenu (22/58; 38%). Une revue systematique de l'efficacite comparative a ete menee pour 31% (9/29) des directives dans les pays a faible et moyen revenu, contre 71% (41/58) des directives dans les pays a haut revenu. Seulement 10% (3/29) des directives emises par les pays a faible et moyen revenu et 19% (11/58) de celles emises par les pays a haut revenu comprenaient un programme d'evaluation des indicateurs de qualite ou de l'adherence aux recommandations. Conclusion La mise en reuvre des directives est mal planifiee, mal analysee et mal mesuree. Reduire les disparites de developpement et de mise en reuvre des directives dans les pays a faible et moyen revenu est une priorite. A l'avenir, ces directives devraient prevoir des strategies d'execution des recommandations, mais aussi d'evaluation de la faisabilite, de la rentabilite et de l'impact sur l'etat de sante. [phrase omitted] Objetivo Evaluar la elaboracion e implementacion de las directrices de practica clinica para el tratamiento de la depresion a nivel mundial. Metodos Se realizo una revision sistematica de las directrices existentes para el tratamiento de la depresion en adultos con trastorno depresivo mayor o bipolar. Por cada directriz identificada, se evaluo el cumplimiento de las medidas de calidad de elaboracion de directrices (como la transparencia en los procesos de elaboracion de directrices y su financiamiento, la composicion del grupo multidisciplinario de autores, la revision sistematica del estudio de eficacia comparativo) y la implementacion (como los indicadores de calidad). En este contexto, se compararon las directrices de los paises de ingresos bajos y medios con las de los paises de ingresos altos. Resultados Se identificaron las directrices de practica clinica a nivel nacional (82) y a nivel internacional (13) de 83 paises en 27 idiomas. Los procesos de elaboracion de directrices y las fuentes de financiamiento se especificaron de manera explicita en un porcentaje menor de directrices de los paises de ingresos bajos y medios (8/29; 28 %) en relacion con las de los paises de ingresos altos (35/58; 60 %). Un grupo de desarrollo multidisciplinario elaboro menos directrices (2/29; 7 %) para los paises de ingresos bajos y medios, en relacion con las de los paises de ingresos altos (22/58; 38 %). Ademas, se realizo una revision sistematica sobre la efectividad comparativa en el 31 % (9/29) de las directrices de los paises de ingresos bajos y medios, frente al 71 % (41/58) de las directrices de los paises de ingresos altos. Solo el 10 % (3/29) de las directrices de los paises de ingresos bajos y medios y el 19 % (11/58) de las directrices de los paises de ingresos altos describieron planes para evaluar los indicadores de calidad o el cumplimiento de las recomendaciones. Conclusion La implementacion de las directrices no se planifica, notifica ni evalua de manera adecuada a nivel mundial. Es prioritario reducir las desigualdades en la elaboracion y la implementacion de las directrices en los paises de ingresos bajos y medios. Las directrices que se elaboren en el futuro deberan presentar estrategias para implementar las recomendaciones y evaluar la viabilidad, la rentabilidad y el impacto en los resultados sanitarios., Introduction The rising prevalence and burden of depression worldwide disproportionately affect low- and middle-income countries. (1-4) Major depressive and bipolar disorders independently increase the risk for other chronic diseases, including [...]
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- 2020
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6. Real-World Effectiveness of Repeated Ketamine Infusions for Treatment-Resistant Bipolar Depression
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Fancy, Farhan, primary, Rodrigues, Nelson B., additional, Di Vincenzo, Joshua D., additional, Chau, Edmond H., additional, Sethi, Rickinder, additional, Husain, Muhammad I., additional, Gill, Hartej, additional, Tabassum, Aniqa, additional, Mckenzie, Andrea, additional, Phan, Lee, additional, McIntyre, Roger S., additional, and Rosenblat, Joshua D., additional
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- 2023
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7. Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions
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McIntyre, Roger S., primary, Alsuwaidan, Mohammad, additional, Baune, Bernhard T., additional, Berk, Michael, additional, Demyttenaere, Koen, additional, Goldberg, Joseph F., additional, Gorwood, Philip, additional, Ho, Roger, additional, Kasper, Siegfried, additional, Kennedy, Sidney H., additional, Ly‐Uson, Josefina, additional, Mansur, Rodrigo B., additional, McAllister‐Williams, R. Hamish, additional, Murrough, James W., additional, Nemeroff, Charles B., additional, Nierenberg, Andrew A., additional, Rosenblat, Joshua D., additional, Sanacora, Gerard, additional, Schatzberg, Alan F., additional, Shelton, Richard, additional, Stahl, Stephen M., additional, Trivedi, Madhukar H., additional, Vieta, Eduard, additional, Vinberg, Maj, additional, Williams, Nolan, additional, Young, Allan H., additional, and Maj, Mario, additional
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- 2023
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8. Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action?
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Husain, Muhammad Ishrat, primary, Ledwos, Nicole, additional, Fellows, Elise, additional, Baer, Jenna, additional, Rosenblat, Joshua D., additional, Blumberger, Daniel M., additional, Mulsant, Benoit H., additional, and Castle, David J., additional
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- 2023
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9. Ketamine for bipolar depression: an updated systematic review.
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Fancy, Farhan, Haikazian, Sipan, Johnson, Danica E., Chen-Li, David C. J., Levinta, Anastasia, Husain, Muhammad I., Mansur, Rodrigo B., and Rosenblat, Joshua D.
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- 2023
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10. A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study)
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Rosenblat, Joshua D., primary, deVries, Froukje E., additional, Doyle, Zoe, additional, McIntyre, Roger S., additional, Rodin, Gary, additional, Zimmermann, Camilla, additional, Mak, Ernie, additional, Hannon, Breffni, additional, Schulz-Quach, Christian, additional, Kindy, Aida Al, additional, Patel, Zeal, additional, and Li, Madeline, additional
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- 2023
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11. An App-Based Digit Symbol Substitution Test for Assessment of Cognitive Deficits in Adults With Major Depressive Disorder: Evaluation Study
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McIntyre, Roger S, primary, Lipsitz, Orly, additional, Rodrigues, Nelson B, additional, Subramaniapillai, Mehala, additional, Nasri, Flora, additional, Lee, Yena, additional, Fehnert, Ben, additional, King, James, additional, Chrones, Lambros, additional, Kratiuk, Kevin, additional, Uddin, Sharif, additional, Rosenblat, Joshua D, additional, Mansur, Rodrigo B, additional, and McCue, Maggie, additional
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- 2022
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12. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder
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Rosenblat, Joshua D., primary, Husain, M. Ishrat, additional, Lee, Yena, additional, McIntyre, Roger S., additional, Mansur, Rodrigo B., additional, Castle, David, additional, Offman, Hilary, additional, Parikh, Sagar V., additional, Frey, Benicio N., additional, Schaffer, Ayal, additional, Greenway, Kyle T., additional, Garel, Nicolas, additional, Beaulieu, Serge, additional, Kennedy, Sidney H., additional, Lam, Raymond W., additional, Milev, Roumen, additional, Ravindran, Arun V., additional, Tourjman, Valerie, additional, Ameringen, Michael Van, additional, Yatham, Lakshmi N., additional, and Taylor, Valerie, additional
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- 2022
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13. The efficacy and safety of adjunctive intranasal esketamine treatment in major depressive disorder: a systematic review and meta-analysis
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Jawad, Muhammad Youshay, Di Vincenzo, Joshua D., Ceban, Felicia, Jaberi, Saja, Lui, Leanna M.W., Gillissie, Emily S., Alnafeesi, Yazen, Rosenblat, Joshua D., and McIntyre, Roger S.
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Depressive Disorder, Major ,Depressive Disorder, Treatment-Resistant ,Humans ,Pharmacology (medical) ,Ketamine ,General Medicine ,Antidepressive Agents - Abstract
Intranasal (IN) esketamine represents an innovative treatment for individuals with treatment resistant depression and depression with suicidal ideation and behavior. Herein, we synthesize extant long-term studies (≥ 4 weeks) regarding this treatment. The interventional studies of IN esketamine in patients with depression having a study period of at least four weeks were included for our synthesis. A meta-analysis was undertaken for the efficacy and safety parameters of adjunctive IN esketamine vs IN placebo with an oral antidepressant. The data excluded from meta-analysis were synthesized narratively. After pooling data from seven randomized controlled trials, treatment with adjunctive IN esketamine vs IN placebo was safe overall, and more effective at decreasing depressive symptoms (d = −0.239; 95%CI = −0.335,-0.142;p < 0.0001), with higher response (RR = 1.221; 95% CI = 1.055,1.428; p = 0.017) and remission (RR = 1.366; 95% CI = 1.182,1.578; p < 0.0001) rates. The year-long trials showed that treatment with adjunctive IN esketamine led to lower relapse rates with no considerable long-term side effects. Intranasal esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior.
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- 2022
14. Ketamine as potential treatment for postpartum depression:A narrative review
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Chen-Li, David, Lui, Leanna M.W., Rosenblat, Joshua D., Lipsitz, Orly, Teopiz, Kayla M., Ho, Roger, Vinberg, Maj, Golts, Marina, Jawad, Muhammad Youshay, Lee, Yena, Nasri, Flora, Gill, Hartej, McIntyre, Roger S., Chen-Li, David, Lui, Leanna M.W., Rosenblat, Joshua D., Lipsitz, Orly, Teopiz, Kayla M., Ho, Roger, Vinberg, Maj, Golts, Marina, Jawad, Muhammad Youshay, Lee, Yena, Nasri, Flora, Gill, Hartej, and McIntyre, Roger S.
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BACKGROUND: Postpartum depression (PPD) is a severe, debilitating mood disorder with consequences for both mothers and children, highlighting the need for rapid-acting and effective treatments for PPD. The aim of this narrative review is to synthesize the available literature on the administration of ketamine for PPD and propose ketamine as a viable and advantageous treatment. METHODS: A search was conducted on MEDLINE/PubMed, PsycInfo, and Embase databases from inception to October 10, 2021 for preclinical studies, interventional studies (ie, open-label and randomized controlled trials), as well as systematic reviews and meta-analyses evaluating the use of ketamine in postpartum populations. Completed and ongoing clinical trials were identified on ClinicalTrials.gov. RESULTS: Four clinical trials were identified. Results from this review support additional investigation into ketamine as a potential treatment for PPD. CONCLUSIONS: Ketamine may be a favorable option for treating PPD due to its antidepressive and analgesic effects, short infusion time, and rapid clearance from the maternal bloodstream. However, there is insufficient evidence to support its use in this population, underscoring the importance of additional clinical research investigating ketamine for PPD.
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- 2022
15. Deficits of social cognition in bipolar disorder:Systematic review and meta-analysis
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Gillissie, Emily S., Lui, Leanna M. W., Ceban, Felicia, Miskowiak, Kamilla, Gok, Sena, Cao, Bing, Teopiz, Kayla M., Ho, Roger, Lee, Yena, Rosenblat, Joshua D., McIntyre, Roger S., Gillissie, Emily S., Lui, Leanna M. W., Ceban, Felicia, Miskowiak, Kamilla, Gok, Sena, Cao, Bing, Teopiz, Kayla M., Ho, Roger, Lee, Yena, Rosenblat, Joshua D., and McIntyre, Roger S.
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Background The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta-analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment. Methods Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM-IV or DSM-5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta-analytic approach. Results A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d = 0.59). The individual domains ranged in effect size (0.38 < d < 0.70), providing evidence for variation in impairment within social cognition. Discussion Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development.
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- 2022
16. Fatigue and cognitive impairment in Post-COVID-19 Syndrome:A systematic review and meta-analysis
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Ceban, Felicia, Ling, Susan, Lui, Leanna M. W., Lee, Yena, Gill, Hartej, Teopiz, Kayla M., Rodrigues, Nelson B., Subramaniapillai, Mehala, Di Vincenzo, Joshua D., Cao, Bing, Lin, Kangguang, Mansur, Rodrigo B., Ho, Roger C., Rosenblat, Joshua D., Miskowiak, Kamilla W., Vinberg, Maj, Maletic, Vladimir, McIntyre, Roger S., Ceban, Felicia, Ling, Susan, Lui, Leanna M. W., Lee, Yena, Gill, Hartej, Teopiz, Kayla M., Rodrigues, Nelson B., Subramaniapillai, Mehala, Di Vincenzo, Joshua D., Cao, Bing, Lin, Kangguang, Mansur, Rodrigo B., Ho, Roger C., Rosenblat, Joshua D., Miskowiak, Kamilla W., Vinberg, Maj, Maletic, Vladimir, and McIntyre, Roger S.
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Importance: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. Objective: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome. Data sources: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists. Study selection: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected. Data extraction & synthesis: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model. Main outcomes & measures: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome. Results: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks
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- 2022
17. The effect of ketamine on anhedonia:improvements in dimensions of anticipatory, consummatory, and motivation-related reward deficits
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Nogo, Danica, Jasrai, Ashitija K., Kim, Haeun, Nasri, Flora, Ceban, Felicia, Lui, Leanna M.W., Rosenblat, Joshua D., Vinberg, Maj, Ho, Roger, McIntyre, Roger S., Nogo, Danica, Jasrai, Ashitija K., Kim, Haeun, Nasri, Flora, Ceban, Felicia, Lui, Leanna M.W., Rosenblat, Joshua D., Vinberg, Maj, Ho, Roger, and McIntyre, Roger S.
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Anhedonia is a common, persistent, and disabling condition. However, available therapeutics primarily focus on the reduction of depressive and negative symptoms rather than amelioration of deficits in positive affect. As such, extant drug treatments remain largely ineffective in treating symptoms of anhedonia. Ketamine is a rapid-acting and novel therapeutic treatment for treatment-resistant depression, which has also been demonstrated to attenuate symptoms of anhedonia. However, the literature on the anti-anhedonic effects of ketamine is limited—especially within independent dimensions of this symptom domain. Herein, this review examined the impact of ketamine treatment on anhedonia and its dimensions on anticipatory, consummatory, and motivation-related reward deficits. Overall, the findings have shown a trend towards symptom reduction and/or improvements in anhedonia and their respective subdomains, in both human and preclinical studies, as well as its potential to provide additional benefit in reducing suicidality and improving quality-of-life. Although further research is required in understanding the long-term efficacy and mechanism, ketamine may provide an effective and rapid-acting therapeutic in an otherwise unmet domain.
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- 2022
18. Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence
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Rodrigues, Nelson B., McIntyre, Roger S., Lipsitz, Orly, Lee, Yena, S., Danielle, Nasri, Flora, Gill, Hartej, Lui, Leanna M.W., Subramaniapillai, Mehala, Kratiuk, Kevin, Lin, Kangguang, Ho, Roger, Mansur, Rodrigo B., and Rosenblat, Joshua D.
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Rigorous clinical trials suggest ketamine is safe and well-tolerated in patients with treatment-resistant depression (TRD). There is a paucity of data on the safety and tolerability of ketamine in community-based clinics treating patients with TRD. Retrospective data was analyzed from 203 patients with TRD who received repeat-dose IV ketamine. Safety was operationalized as hemodynamic changes. Tolerability was evaluated through the reporting of adverse events and dissociation symptom severity, as measured by the Clinician-Administered Dissociative States Scale. Ketamine was well-tolerated, with less than 5% of patients withdrawing due to tolerability concerns. Blood pressure significantly increased during infusion, with 44.3% meeting criteria for treatment-emergent hypertension (i.e., blood pressure ≥ 165/100 mmHg). 12% of patients exhibiting hypertension required pharmacological intervention. The most frequently reported adverse events included drowsiness (56.4%), dizziness (45.2%), dissociation (35.6%), and nausea (13.3%). Dissociation severity significantly attenuated after the first infusion, but plateaued for subsequent infusions. Intravenous ketamine was safe and well-tolerated. Hypertension was commonly observed and was often transient. Dissociation was most frequently reported after the first infusion but remained a consistent but not treatment-limiting adverse event thereafter. No patients exhibited psychosis, mania, or new onset suicidality with IV ketamine.
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- 2022
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19. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder.
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Rosenblat, Joshua D., Husain, M. Ishrat, Lee, Yena, McIntyre, Roger S., Mansur, Rodrigo B., Castle, David, Offman, Hilary, Parikh, Sagar V., Frey, Benicio N., Schaffer, Ayal, Greenway, Kyle T., Garel, Nicolas, Beaulieu, Serge, Kennedy, Sidney H., Lam, Raymond W., Milev, Roumen, Ravindran, Arun V., Tourjman, Valerie, Ameringen, Michael Van, and Yatham, Lakshmi N.
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MENTAL depression , *TASK forces , *LSD (Drug) , *PSILOCYBIN , *HALLUCINOGENIC drugs , *ANXIETY disorders - Abstract
Objective: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. Methods: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. Results: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. Conclusions: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Suicide reduction in Canada during the COVID-19 pandemic: lessons informing national prevention strategies for suicide reduction
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McIntyre, Roger S, primary, Lui, Leanna MW, additional, Rosenblat, Joshua D, additional, Ho, Roger, additional, Gill, Hartej, additional, Mansur, Rodrigo B, additional, Teopiz, Kayla, additional, Liao, Yuhua, additional, Lu, Ciyong, additional, Subramaniapillai, Mehala, additional, Nasri, Flora, additional, and Lee, Yena, additional
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- 2021
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21. sj-pdf-1-jrs-10.1177_01410768211043186 - Supplemental material for Suicide reduction in Canada during the COVID-19 pandemic: lessons informing national prevention strategies for suicide reduction
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McIntyre, Roger S, Lui, Leanna MW, Rosenblat, Joshua D, Ho, Roger, Gill, Hartej, Mansur, Rodrigo B, Teopiz, Kayla, Liao, Yuhua, Lu, Ciyong, Subramaniapillai, Mehala, Nasri, Flora, and Lee, Yena
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Medicine - Abstract
Supplemental material, sj-pdf-1-jrs-10.1177_01410768211043186 for Suicide reduction in Canada during the COVID-19 pandemic: lessons informing national prevention strategies for suicide reduction by Roger S McIntyre, Leanna MW Lui, Joshua D Rosenblat, Roger Ho, Hartej Gill, Rodrigo B Mansur, Kayla Teopiz, Yuhua Liao, Ciyong Lu, Mehala Subramaniapillai, Flora Nasri and Yena Lee in Journal of the Royal Society of Medicine
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- 2021
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22. Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression
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McMullen, Eric P., Lee, Yena, Lipsitz, Orly, Lui, Leanna M.W., Vinberg, Maj, Ho, Roger, Rodrigues, Nelson B., Rosenblat, Joshua D., Cao, Bing, Gill, Hartej, Teopiz, Kayla M., Cha, Danielle S., McIntyre, Roger S., McMullen, Eric P., Lee, Yena, Lipsitz, Orly, Lui, Leanna M.W., Vinberg, Maj, Ho, Roger, Rodrigues, Nelson B., Rosenblat, Joshua D., Cao, Bing, Gill, Hartej, Teopiz, Kayla M., Cha, Danielle S., and McIntyre, Roger S.
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Introduction: Ketamine treatment is capable of significant and rapid symptom improvement in adults with treatment-resistant depression (TRD). A limitation of ketamine treatment in TRD is the relatively short duration of time to relapse (e.g., median 2–4 weeks). The objective of the systematic review herein is to identify strategies capable of prolonging the acute efficacy of ketamine in adults with TRD. Methods: PubMed/MEDLINE databases were searched from inception to December 2020 for clinical studies written in English using the following key terms: ketamine, prolong, and depression. A total of 454 articles were identified from the literature search which included all clinical studies regarding prolonging the antidepressant effects of ketamine. Twenty-two articles were included: ten randomized controlled trials (RCTs), eight prospective open-label trials, one retrospective chart review, and three case reports. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data extraction. The primary outcome was prolonged effect, defined as statistically significant antidepressant effects following acute ketamine treatment. Results: A total of 454 articles were identified, and 22 articles were included. Different treatment modalites including pharmacological interventions, manualized-based psychotherapies, electroconvulsive therapy, transcranial magnetic stimulation, and intravenous monotherapy were examined to determine their impact on the prolongation of antidepressant effects following acute ketamine treatment. No treatment modality, other than repeat-dose IV ketamine, has demonstrated ability to significantly prolong the acute efficacy of IV ketamine in TRD. Conclusion: Hitherto, available open-label data and controlled trial data support repeat administration of IV ketamine as an effective strategy to prolong the efficacy of ketamine’s antidepressant effects (although not the focus of the study herein, maintenance
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- 2021
23. 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, Nelson B., McIntyre, Roger S., Lipsitz, Orly, Lee, Yena, Cha, Danielle S., Shekotikhina, Margarita, Vinberg, Maj, Gill, Hartej, Subramaniapillai, Mehala, Kratiuk, Kevin, Lin, Kangguang, Ho, Roger, Mansur, Rodrigo B., Rosenblat, Joshua D., Rodrigues, Nelson B., McIntyre, Roger S., Lipsitz, Orly, Lee, Yena, Cha, Danielle S., Shekotikhina, Margarita, Vinberg, Maj, Gill, Hartej, Subramaniapillai, Mehala, Kratiuk, Kevin, Lin, Kangguang, Ho, Roger, Mansur, Rodrigo B., and Rosenblat, Joshua D.
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Background: Dissociation is a treatment-emergent adverse event commonly associated with IV ketamine, often measured using the 23-item Clinician-Administered Dissociative States Scale (CADSS). The objective of this study was to develop a short form version of the CADSS for easier clinical use. Methods: Retrospective data of 260 patients with 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.
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- 2021
24. Impact of SARS-CoV-2 Infection on Cognitive Function: A Systematic Review
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Alnefeesi, Yazen, primary, Siegel, Ashley, additional, Lui, Leanna M. W., additional, Teopiz, Kayla M., additional, Ho, Roger C. M., additional, Lee, Yena, additional, Nasri, Flora, additional, Gill, Hartej, additional, Lin, Kangguang, additional, Cao, Bing, additional, Rosenblat, Joshua D., additional, and McIntyre, Roger S., additional
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- 2021
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25. Depression in the medically ill
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Rosenblat, Joshua D., Kurdyak, Paul, Cosci, Fiammetta, Berk, Michael, Maes, Michael, Brunoni, Andre R., Li, Madeline, Rodin, Gary, McIntyre, Roger S., Carvalho, Andre F., Rosenblat, Joshua D., Kurdyak, Paul, Cosci, Fiammetta, Berk, Michael, Maes, Michael, Brunoni, Andre R., Li, Madeline, Rodin, Gary, McIntyre, Roger S., and Carvalho, Andre F.
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- 2020
26. Bipolar disorders
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McIntyre, Roger S., Berk, Michael, Brietzke, Elisa, Goldstein, Benjamin I., López-Jaramillo, Carlos, Kessing, Lars Vedel, Malhi, Gin S., Nierenberg, Andrew A., Rosenblat, Joshua D., Majeed, Amna, Vieta, Eduard, Vinberg, Maj, Young, Allan H., Mansur, Rodrigo B., McIntyre, Roger S., Berk, Michael, Brietzke, Elisa, Goldstein, Benjamin I., López-Jaramillo, Carlos, Kessing, Lars Vedel, Malhi, Gin S., Nierenberg, Andrew A., Rosenblat, Joshua D., Majeed, Amna, Vieta, Eduard, Vinberg, Maj, Young, Allan H., and Mansur, Rodrigo B.
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Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10–20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acut
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- 2020
27. The effectiveness of ketamine on anxiety, irritability, and agitation:Implications for treating mixed features in adults with major depressive or bipolar disorder
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McIntyre, Roger S., Lipsitz, Orly, Rodrigues, Nelson B., Lee, Yena, Cha, Danielle S., Vinberg, Maj, Lin, Kangguang, Malhi, Gin S., Subramaniapillai, Mehala, Kratiuk, Kevin, Fagiolini, Andrea, Gill, Hartej, Nasri, Flora, Mansur, Rodrigo B., Suppes, Trisha, Ho, Roger, Rosenblat, Joshua D., McIntyre, Roger S., Lipsitz, Orly, Rodrigues, Nelson B., Lee, Yena, Cha, Danielle S., Vinberg, Maj, Lin, Kangguang, Malhi, Gin S., Subramaniapillai, Mehala, Kratiuk, Kevin, Fagiolini, Andrea, Gill, Hartej, Nasri, Flora, Mansur, Rodrigo B., Suppes, Trisha, Ho, Roger, and Rosenblat, Joshua D.
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Objective: To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD). Method: Adults (N = 201) with treatment-resistant MDD or BD received repeat-dose IV ketamine treatment at a community-based clinic. Mixed features were measured using symptoms of anxiety, irritability, and agitation (AIA), as measured by the Generalized Anxiety Disorder-7 (GAD-7) scale. The Quick Inventory for Depressive Symptomatology Self-Report-16 (QIDS-SR16) was used to measure overall treatment response, and the QIDS-SR16 suicidal ideation (SI) item was used to measure change in SI symptoms with ketamine treatment. The anxiety, irritability, and agitation items on the GAD-7 were used to assess effectiveness of IV ketamine in treating symptoms of mixed features. Results: In this retrospective analysis, 113 participants met AIA criteria. Participants with AIA experienced a significantly greater reduction in overall depressive symptoms (F(1, 558) = 9.49, P =.002), SI (F(1, 558) = 3.103, P =.079), anxiety (F(1, 198) = 5.52, P =.007), irritability (F(1, 198) = 28.35, P <.001), and agitation as measured by “trouble relaxing” (F(1, 198) = 6.70, P =.010) from baseline compared to the non-AIA group, regardless of number of treatments received. Conclusions: Our preliminary results suggest that IV ketamine is effective in rapidly treating AIA and SI in adults with treatment-resistant mood disorders. This observation suggests that IV ketamine could be considered a treatment alternative for adults with MDD or BD presenting with mixed features.
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- 2020
28. Synergistic effect of social media use and psychological distress on depression in China during the COVID ‐19 epidemic
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Lee, Yena, primary, Yang, Bing Xiang, additional, Liu, Qian, additional, Luo, Dan, additional, Kang, Lijun, additional, Yang, Fang, additional, Ma, Simeng, additional, Lu, Weicong, additional, Chen‐Li, David, additional, Rosenblat, Joshua D., additional, Mansur, Rodrigo B., additional, Nasri, Flora, additional, Subramaniapillai, Mehala, additional, Liu, Zhongchun, additional, McIntyre, Roger S., additional, and Lin, Kangguang, additional
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- 2020
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29. The THINC-it Tool for Cognitive Assessment and Measurement in Major Depressive Disorder: Sensitivity to Change
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McIntyre, Roger S., primary, Subramaniapillai, Mehala, additional, Park, Caroline, additional, Zuckerman, Hannah, additional, Cao, Bing, additional, Lee, Yena, additional, Iacobucci, Michelle, additional, Nasri, Flora, additional, Fus, Dominika, additional, Bowie, Christopher R., additional, Tran, Tanya, additional, Rosenblat, Joshua D., additional, and Mansur, Rodrigo B., additional
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- 2020
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30. Extracellular Vesicle Biomarkers Reveal Inhibition of Neuroinflammation by Infliximab in Association with Antidepressant Response in Adults with Bipolar Depression
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Mansur, Rodrigo B., primary, Delgado-Peraza, Francheska, additional, Subramaniapillai, Mehala, additional, Lee, Yena, additional, Iacobucci, Michelle, additional, Rodrigues, Nelson, additional, Rosenblat, Joshua D., additional, Brietzke, Elisa, additional, Cosgrove, Victoria E., additional, Kramer, Nicole E., additional, Suppes, Trisha, additional, Raison, Charles L., additional, Chawla, Sahil, additional, Nogueras-Ortiz, Carlos, additional, McIntyre, Roger S., additional, and Kapogiannis, Dimitrios, additional
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- 2020
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31. Revising Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for the bipolar disorders:Phase I of the AREDOC project
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Parker, Gordon, Tavella, Gabriela, Macqueen, Glenda, Berk, Michael, Grunze, Heinz, Deckersbach, Thilo, Dunner, David L, Sajatovic, Martha, Amsterdam, Jay D, Ketter, Terence A, Yatham, Lakshmi N, Kessing, Lars Vedel, Bassett, Darryl, Zimmerman, Mark, Fountoulakis, Kostas N, Duffy, Anne, Alda, Martin, Calkin, Cynthia, Sharma, Verinder, Anand, Amit, Singh, Manpreet K, Hajek, Tomas, Boyce, Philip, Frey, Benicio N, Castle, David J, Young, Allan H, Vieta, Eduard, Rybakowski, Janusz K, Swartz, Holly A, Schaffer, Ayal, Murray, Greg, Bayes, Adam, Lam, Raymond W, Bora, Emre, Post, Robert M, Ostacher, Michael J, Lafer, Beny, Cleare, Anthony J, Burdick, Katherine E, O'Donovan, Claire, Ortiz, Abigail, Henry, Chantal, Kanba, Shigenobu, Rosenblat, Joshua D, Parikh, Sagar V, Bond, David J, Grunebaum, Michael F, Frangou, Sophia, Goldberg, Joseph F, Orum, Margo, Osser, David N, Frye, Mark A, McIntyre, Roger S, Fagiolini, Andrea, Manicavasagar, Vijaya, Carlson, Gabrielle A, Malhi, Gin S, Parker, Gordon, Tavella, Gabriela, Macqueen, Glenda, Berk, Michael, Grunze, Heinz, Deckersbach, Thilo, Dunner, David L, Sajatovic, Martha, Amsterdam, Jay D, Ketter, Terence A, Yatham, Lakshmi N, Kessing, Lars Vedel, Bassett, Darryl, Zimmerman, Mark, Fountoulakis, Kostas N, Duffy, Anne, Alda, Martin, Calkin, Cynthia, Sharma, Verinder, Anand, Amit, Singh, Manpreet K, Hajek, Tomas, Boyce, Philip, Frey, Benicio N, Castle, David J, Young, Allan H, Vieta, Eduard, Rybakowski, Janusz K, Swartz, Holly A, Schaffer, Ayal, Murray, Greg, Bayes, Adam, Lam, Raymond W, Bora, Emre, Post, Robert M, Ostacher, Michael J, Lafer, Beny, Cleare, Anthony J, Burdick, Katherine E, O'Donovan, Claire, Ortiz, Abigail, Henry, Chantal, Kanba, Shigenobu, Rosenblat, Joshua D, Parikh, Sagar V, Bond, David J, Grunebaum, Michael F, Frangou, Sophia, Goldberg, Joseph F, Orum, Margo, Osser, David N, Frye, Mark A, McIntyre, Roger S, Fagiolini, Andrea, Manicavasagar, Vijaya, Carlson, Gabrielle A, and Malhi, Gin S
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OBJECTIVE:: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations.METHOD:: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified.RESULTS:: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge 'impairment' (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders.CONCLUSION:: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.
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- 2018
32. Ketogenic diet as a metabolic therapy for mood disorders:Evidence and developments
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Brietzke, Elisa, Mansur, Rodrigo B, Subramaniapillai, Mehala, Balanzá-Martínez, Vicent, Vinberg, Maj, González-Pinto, Ana, Rosenblat, Joshua D, Ho, Roger, McIntyre, Roger S, Brietzke, Elisa, Mansur, Rodrigo B, Subramaniapillai, Mehala, Balanzá-Martínez, Vicent, Vinberg, Maj, González-Pinto, Ana, Rosenblat, Joshua D, Ho, Roger, and McIntyre, Roger S
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Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations.
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- 2018
33. Serum metabolic profiling using small molecular water-soluble metabolites in individuals with schizophrenia: A longitudinal study using a pre-post-treatment design
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Cao, Bing, primary, Jin, Min, additional, Brietzke, Elisa, additional, McIntyre, Roger S., additional, Wang, Dongfang, additional, Rosenblat, Joshua D., additional, Ragguett, Renee-Marie, additional, Zhang, Chuanbo, additional, Sun, Xiaoyu, additional, Rong, Carola, additional, and Wang, Jingyu, additional
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- 2018
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34. Serum metabolic profiling using small molecular water‐soluble metabolites in individuals with schizophrenia: A longitudinal study using a pre–post‐treatment design.
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Cao, Bing, Jin, Min, Brietzke, Elisa, McIntyre, Roger S., Wang, Dongfang, Rosenblat, Joshua D., Ragguett, Renee‐Marie, Zhang, Chuanbo, Sun, Xiaoyu, Rong, Carola, and Wang, Jingyu
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METABOLIC profile tests - Abstract
Aim: We sought to compare alterations in serum bioenergetic markers within a well‐characterized sample of adults with schizophrenia at baseline and after 8 weeks of pharmacological treatment with the hypothesis that treatment would be associated with significant changes in bioenergetic markers given the role of bioenergetic dysfunction in schizophrenia. Methods: We recruited adults with schizophrenia (n = 122) who had not received pharmacological treatment for at least 1 month prior to enrollment, including drug‐naïve (i.e., first‐episode) participants and treatment non‐adherent participants. Pre‐ and post‐treatment serum samples were analyzed using liquid chromatography–tandem mass spectrometry. Results: Metabolites with the greatest change, when comparing pre‐ and post‐treatment levels, were identified revealing 14 water‐soluble metabolites of interest. The composition of these metabolites was: amino acids (n = 6), carnitines (n = 4), polar lipids (n = 3), and organic acid (n = 1). All amino acids and lysophosphatidylcholines (LysoPC) were increased, while the four carnitines – oleoylcarnitine, L‐palmitoylcarnitine, linoleyl carnitine, and L‐acetylcarnitine – were decreased post‐treatment. Of these metabolite biomarkers, six – oleoylcarnitine, linoleyl carnitine, L‐acetylcarnitine, LysoPC(15:0), D‐glutamic acid, and L‐arginine – were identified as having most consistently and predictably changed after 8 weeks of treatment. Conclusion: The current study identified several bioenergetic markers that consistently change with pharmacological treatment. These bioenergetic changes may provide further insights into the pathophysiology of schizophrenia along with furthering our understanding of the mechanisms subserving both the effects (e.g., antipsychotic effects) and side‐effects (e.g., metabolic syndrome) of antipsychotics. [ABSTRACT FROM AUTHOR]
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- 2019
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35. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes
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Lam, Raymond W., Kennedy, Sidney H., Adams, Camelia, Bahji, Anees, Beaulieu, Serge, Bhat, Venkat, Blier, Pierre, Blumberger, Daniel M., Brietzke, Elisa, Chakrabarty, Trisha, Do, André, Frey, Benicio N., Giacobbe, Peter, Gratzer, David, Grigoriadis, Sophie, Habert, Jeffrey, Ishrat Husain, M., Ismail, Zahinoor, McGirr, Alexander, McIntyre, Roger S., Michalak, Erin E., Müller, Daniel J., Parikh, Sagar V., Quilty, Lena S., Ravindran, Arun V., Ravindran, Nisha, Renaud, Johanne, Rosenblat, Joshua D., Samaan, Zainab, Saraf, Gayatri, Schade, Kathryn, Schaffer, Ayal, Sinyor, Mark, Soares, Claudio N., Swainson, Jennifer, Taylor, Valerie H., Tourjman, Smadar V., Uher, Rudolf, van Ameringen, Michael, Vazquez, Gustavo, Vigod, Simone, Voineskos, Daphne, Yatham, Lakshmi N., and Milev, Roumen V.
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Background The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults.Methods CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process.Results The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted.Conclusions The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.
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- 2024
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36. Anti-inflammatory agents in the treatment of bipolar depression:a systematic review and meta-analysis
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Rosenblat, Joshua D, Kakar, Ron, Berk, Michael, Kessing, Lars V, Vinberg, Maj, Baune, Bernhard T, Mansur, Rodrigo B, Brietzke, Elisa, Goldstein, Benjamin I, McIntyre, Roger S, Rosenblat, Joshua D, Kakar, Ron, Berk, Michael, Kessing, Lars V, Vinberg, Maj, Baune, Bernhard T, Mansur, Rodrigo B, Brietzke, Elisa, Goldstein, Benjamin I, and McIntyre, Roger S
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OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression.METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone.RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported.CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
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- 2016
37. Assessing and measuring cognitive function in major depressive disorder
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Ragguett, Renee-Marie, primary, Cha, Danielle S, additional, Kakar, Ron, additional, Rosenblat, Joshua D, additional, Lee, Yena, additional, and McIntyre, Roger S, additional
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- 2016
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38. Deconstructing Diabetes and Depression: Clinical Context, Treatment Strategies, and New Directions
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Gregory, Jonathan M., primary, Rosenblat, Joshua D., additional, and McIntyre, Roger S., additional
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- 2016
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39. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients
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Woo, Young Sup, primary, Rosenblat, Joshua D., additional, Kakar, Ron, additional, Bahk, Won-Myong, additional, and McIntyre, Roger S., additional
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- 2016
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40. Therapeutic Angiogenesis by Ultrasound-Mediated MicroRNA-126-3p Delivery
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Cao, Wei J., primary, Rosenblat, Joshua D., additional, Roth, Nathan C., additional, Kuliszewski, Michael A., additional, Matkar, Pratiek N., additional, Rudenko, Dmitriy, additional, Liao, Christine, additional, Lee, Paul J.H., additional, and Leong-Poi, Howard, additional
- Published
- 2015
- Full Text
- View/download PDF
41. Bipolar Disorder and Immune Dysfunction: Epidemiological Findings, Proposed Pathophysiology and Clinical Implications.
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Rosenblat, Joshua D. and McIntyre, Roger S.
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- *
BIPOLAR disorder , *IMMUNOLOGIC diseases , *PATHOLOGICAL physiology - Abstract
Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA) axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a subset of BD patients and as such, future clinical trials should also strive to identify which specific group(s) of BD patients may benefit from anti-inflammatory treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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42. The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
- Author
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Rosenblat, Joshua D, primary, Kakar, Ron, additional, and McIntyre, Roger S, additional
- Published
- 2015
- Full Text
- View/download PDF
43. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients.
- Author
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Young Sup Woo, Rosenblat, Joshua D., Kakar, Ron, Won-Myong Bahk, and McIntyre, Roger S.
- Subjects
- *
MENTAL depression , *THERAPEUTICS , *DISEASE remission , *DEPRESSED persons - Abstract
Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
44. The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta- Analysis of Randomized Clinical Trials.
- Author
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Rosenblat, Joshua D., Kakar, Ron, and McIntyre, Roger S.
- Subjects
ANTIDEPRESSANTS ,COGNITIVE analysis ,MENTAL depression ,CLINICAL trials ,META-analysis - Abstract
Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05-0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15-0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
45. Targeting the Immune System in Depression: Promising and Primetime.
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Rosenblat, Joshua D. and McIntyre, Roger S.
- Subjects
- *
ANTIDEPRESSANTS , *HEPATITIS treatment , *MONOAMINE oxidase inhibitors , *TUMOR treatment , *AFFECT (Psychology) , *AFFECTIVE disorders , *ALTERNATIVE medicine , *AUTOIMMUNE diseases , *COGNITION disorders , *MENTAL depression , *IMMUNE system , *INFLAMMATION , *MENTAL illness , *NATURAL immunity , *PSORIASIS , *RHEUMATOID arthritis , *DRUG development , *DISEASE relapse , *DISEASE remission , *THERAPEUTICS - Published
- 2018
46. Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder.
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Rong, Carola, Park, Caroline, Rosenblat, Joshua D., Subramaniapillai, Mehala, Zuckerman, Hannah, Fus, Dominika, Lee, Yena L., Pan, Zihang, Brietzke, Elisa, Mansur, Rodrigo B., Cha, Danielle S., Lui, Leanna M. W., and McIntyre, Roger S.
- Published
- 2018
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47. Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial.
- Author
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Husain MI, Blumberger DM, Castle DJ, Ledwos N, Fellows E, Jones BDM, Ortiz A, Kloiber S, Wang W, Rosenblat JD, and Mulsant BH
- Abstract
Background: Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone., Aims: To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone)., Method: In a 4-week, three-arm, 'double dummy' trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure., Results: This trial will advance the understanding of psilocybin's mechanism of antidepressant action., Conclusions: This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.
- Published
- 2023
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48. Assessing and measuring cognitive function in major depressive disorder.
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Ragguett RM, Cha DS, Kakar R, Rosenblat JD, Lee Y, and McIntyre RS
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- Humans, Mobile Applications, Cognitive Dysfunction diagnosis, Depressive Disorder, Major psychology, Mass Screening methods, Psychological Tests
- Abstract
Cognitive dysfunction is a major component of major depressive disorder (MDD). No 'gold-standard' tool exists for the assessment of cognitive dysfunction for adults with MDD. The use of measurement-based care to improve treatment outcomes invites the need for a systematic screening, evaluation and measurement tool. The aim herein was to provide a succinct summary of literature documenting clinical implication of cognitive dysfunction in MDD, and a review of available screening, diagnostic and measurement tools for cognitive dysfunction in MDD is provided. We also take the opportunity to introduce a screening tool (ie, the THINC-it tool) targeted at addressing the unmet needs. We found that there are limitations to the current measurement scales; for example, many are not targeted for MDD and not all digitally available tests are free of charge. Furthermore, the spectrum of cognitive dysfunction in MDD is poorly represented by the existing tests and as such, there is a lack of sensitivity in the ability to screen a patient with MDD for a cognitive dysfunction. Recognising and addressing the limitations in the current screening techniques for cognitive dysfunction as well as being presented with the current tools available provides the ability to perform an educated cognitive screening for a patient with MDD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
- Published
- 2016
- Full Text
- View/download PDF
49. Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review.
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Rosenblat JD, McIntyre RS, Alves GS, Fountoulakis KN, and Carvalho AF
- Subjects
- Animals, Biogenic Monoamines antagonists & inhibitors, Depressive Disorder, Treatment-Resistant drug therapy, Humans, Antidepressive Agents therapeutic use, Biogenic Monoamines metabolism, Depressive Disorder, Treatment-Resistant metabolism
- Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown.
- Published
- 2015
- Full Text
- View/download PDF
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