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Roger S McIntyre

University of Toronto, University Health Network

131 papers in the library · 4,810 citations · publishing 0-2026

Papers

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Effect of intravenous ketamine on suicidality in adults with treatment-resistant depression: A real world effectiveness study.

Psychiatry Research 2025 David C J Chen-Li, Rodrigo B. Mansur, Joshua D. Di Vincenzo et al. 6 citations

Suicidal ideation is a significant symptom associated with mood disorders. Ketamine is an emerging treatment with rapid and robust antidepressant and antisuicidal effects observed in clinical trial populations. Herein we assessed the real-world effectiveness of ketamine in ameliorating suicidality. A retroactive chart analysis of 96 adult TRD patients that received treatment in a private...

Effects of ketamine on metabolic parameters in depressive disorders: A systematic review.

Journal of Affective Disorders December 15, 2024 Sabrina Wong, Gia Han Le, Rodrigo B. Mansur et al. 3 citations

Persons with Major Depressive Disorder (MDD), notably treatment-resistant depression (TRD), are differentially affected by type 2 diabetes mellitus and associated morbidity. Ketamine is highly efficacious in the treatment of adults living with MDD, notably TRD. Herein, we sought to determine the effect of ketamine on metabolic parameters in animal stress paradigms and human studies. We...

Ketamine for the Treatment of Psychiatric Disorders: A Systematic Review and Meta-Analysis.

CNS Spectrums November 20, 2024 Angela T H Kwan, Moiz Lakhani, Gurkaran Singh et al. 4 citations

Inadequate response to first- and second-line pharmacological treatments for psychiatric disorders is commonly observed. Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression (TRD), with additional off-label benefits reported for various psychiatric disorders. Herein, we performed a systematic review and meta-analysis to examine the therapeutic applications...

Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder

Psychedelic Medicine November 18, 2024 Shakila Meshkat, Erica Kaczmarek, Zoe Doyle et al. 8 citations

Background: Bipolar II disorder (BD-II) is often associated with chronic and treatment resistant major depressive episodes. Psilocybin has shown promise for its rapid-acting antidepressant effects, though its impact on bipolar depression remains unexplored. In the present subgroup analysis of an already published trial on treatment-resistant depression (TRD), we aimed to preliminarily evaluate...

Glutamatergic Modulators for Major Depression from Theory to Clinical Use.

CNS Drugs November 1, 2024 Roger S McIntyre, Rakesh Jain 58 citations

Major depressive disorder (MDD) is a chronic, burdensome, highly prevalent disease that is characterized by depressed mood and anhedonia. MDD is especially burdensome as approved monoamine antidepressant treatments have weeks-long delays before clinical benefit and low remission rates. In the past 2 decades, a promising target emerged to improve patient outcomes in depression treatment:...

Efficacy of esketamine for perinatal depression: a systematic review and meta-analysis.

CNS Spectrums October 31, 2024 Sabrina Wong, Gia Han Le, Angela T H Kwan et al. 10 citations

Postpartum depression (PPD), now referred to as perinatal depression, is a prevalent and debilitating mood disorder that reduces health-related quality of life (HRQoL) and psychosocial functioning. Esketamine, which is efficacious in adults with treatment-resistant depression and individuals with depression and suicidality, is also analgesic in pain management during childbirth labour. Herein,...

A replication study using the World Health Organization pharmacovigilance database (VigiBase®) to evaluate whether an association between ketamine and esketamine and alcohol and substance misuse exists.

Journal of Affective Disorders October 15, 2024 Angela T H Kwan, Joshua D. Rosenblat, Rodrigo B. Mansur et al. 13 citations

Ketamine and esketamine are increasingly prescribed in the treatment of resistant mood disorders and persons at risk of suicide. Ketamine is a drug of misuse with increasing non-therapeutic use in the general population. Herein, our aim was to determine whether ketamine and/or esketamine are disproportionately associated with reports of substance and/or alcohol misuse. Replicating a similar...

The Association Between Dextromethorphan/Bupropion with Alcohol and Substance Misuse: Reports to the Food and Drug Administration Adverse Event Reporting System (FAERS)

CNS Spectrums October 1, 2024 Angela T.H. Kwan, Roger S. McIntyre

AbstractObjectiveDextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to...

The association between ketamine and esketamine with alcohol and substance misuse: Reports to the Food and Drug Administration adverse event reporting system (FAERS).

Journal of Affective Disorders September 1, 2024 Angela T H Kwan, Joshua D. Rosenblat, Rodrigo B. Mansur et al. 8 citations

Ketamine and esketamine have been proven to be effective in treating adults with treatment resistant depression (TRD). Preliminary evidence indicates that, when combined with behavioral and psychological interventions, both agents may offer benefits for individuals with substance use disorder (SUD) and alcohol use disorder (AUD). Notwithstanding, concerns have been raised as to whether either...

Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.

Translational Psychiatry August 6, 2024 Chengyu Wang, Xiaofeng Lan, Weijian Liu et al. 6 citations

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar...

Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology August 1, 2024 Roger S McIntyre, Istvan Bitter, Jozefien Buyze et al. 30 citations

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the...

Protocols and practices in psilocybin assisted psychotherapy for depression: A systematic review.

Journal of Psychiatric Research August 1, 2024 Noah Chisamore, Danica E. Johnson, Margery J.q. Chen et al. 21 citations

Psilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in...

Number needed to treat (NNT) for ketamine and esketamine in adults with treatment-resistant depression: A systematic review and meta-analysis.

Journal of Affective Disorders July 1, 2024 Cameron N Calder, Angela T H Kwan, Kayla M Teopiz et al. 31 citations

Ketamine has been established as efficacious in adults living with Treatment-resistant Depression (TRD). Toward providing a quantifiable estimate of the clinical meaningfulness of the therapeutic benefit of ketamine, herein, we conduct a systematic review that aims to report the Number Needed to Treat (NNT) and the Number Needed to Harm (NNH). This systematic review searched Embase,...

The association between ketamine and esketamine and suicidality: reports to the Food And Drug Administration Adverse Event Reporting System (FAERS).

Expert Opinion on Drug Safety June 21, 2024 Roger S McIntyre, Rodrigo B. Mansur, Joshua D. Rosenblat et al. 7 citations

Replicated evidence indicates that ketamine and esketamine reduce measures of suicidality in persons with treatment-resistant depression (TRD). It remains uncertain whether individuals experience worsening of preexisting suicidality with either agent. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was searched from 1970 and 2019 to 30 September 2023 for reports...

Spectral signatures of psilocybin, lysergic acid diethylamide (LSD) and ketamine in healthy volunteers and persons with major depressive disorder and treatment-resistant depression: A systematic review.

Journal of Affective Disorders June 15, 2024 Gia Han Le, Sabrina Wong, Sebastian Badulescu et al. 25 citations

Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents. We...

Predicting non-response to ketamine for depression: An exploratory symptom-level analysis of real-world data among military veterans.

Psychiatry Research May 1, 2024 Eric A. Miller, Houtan Totonchi Afshar, Jyoti Mishra et al. 12 citations

Ketamine helps some patients with treatment resistant depression (TRD), but reliable methods for predicting which patients will, or will not, respond to treatment are lacking. Herein, we aim to inform prediction models of non-response to ketamine/esketamine in adults with TRD. This is a retrospective analysis of PHQ-9 item response data from 120 patients with TRD who received repeated doses of...

Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023

Current Psychiatry Reports April 1, 2024 John L. Havlik, Syed Wahid, Kayla M Teopiz et al. 30 citations

Purpose of Review We review recent advances in the treatment of treatment-resistant depression (TRD), a disorder with very limited treatment options until recently. We examine advances in psychotherapeutic, psychopharmacologic, and interventional psychiatry approaches to treatment of TRD. We also highlight various definitions of TRD in recent scientific literature. Recent Findings Recent...

A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review.

Journal of Affective Disorders April 1, 2024 Sabrina Wong, Angela T H Kwan, Kayla M Teopiz et al. 19 citations

Inadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a proven treatment recently approved for adults with Treatment-Resistant Depression (TRD) while psilocybin is an investigational treatment. Translation of the clinical meaningfulness for these foregoing agents in adults with TRD is...

Brain-derived neurotrophic factor Val66Met and CYP2B6 polymorphisms as predictors for ketamine effectiveness in patients with treatment-resistant depression.

Journal of psychopharmacology (Oxford, England) April 1, 2024 Nelson B Rodrigues, David C J Chen-Li, Joshua D. Di Vincenzo et al. 12 citations

Converging lines of evidence indicate that ketamine is a rapid antidepressant for individuals with treatment-resistant depression. Hitherto, no reliable a priori predictors of ketamine response have been reported. Pharmacogenetic biomarkers have yielded mixed results regarding potential candidate genes associated with ketamine's biochemistry as reliable predictors of response. No studies have...

Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

Med (New York, N.Y.) March 8, 2024 Joshua D. Rosenblat, Shakila Meshkat, Zoe Doyle et al. 97 citations

Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity....

The effects of Lysergic Acid Diethylamide (LSD) on the Positive Valence Systems: A Research Domain Criteria (RDoC)-Informed Systematic Review.

CNS Drugs December 1, 2023 Niloufar Pouyan, Farnaz Younesi Sisi, Alireza Kargar et al. 12 citations

The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research Domain Criteria (RDoC) framework, as proposed by the National Institute of Mental Health, we aim to synthesize the existing literature concerning the impact of lysergic acid diethylamide (LSD) on the RDoC's Positive Valence...

Psilocybin-assisted therapy for depression: A systematic review and meta-analysis.

Psychiatry Research November 1, 2023 Sipan Haikazian, David C J Chen-Li, Danica E. Johnson et al. 121 citations

The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome...

Real-World Effectiveness of Repeated Ketamine Infusions for Treatment-Resistant Bipolar Depression.

Focus (American Psychiatric Publishing) October 1, 2023 Farhan Fancy, Nelson B Rodrigues, Joshua D. Di Vincenzo et al. 4 citations

Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression. This study was conducted in a community clinic in Mississauga, Ontario (Canadian...

Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials.

CNS Drugs October 1, 2023 Dania Akbar, Taeho Greg Rhee, Felicia Ceban et al.

A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants. The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion,...

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

World Psychiatry September 15, 2023 Roger S McIntyre, Mohammad Alsuwaidan, Bernhard T Baune et al. 712 citations

Treatment‐resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision‐making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a...