JAMA Psychiatry
September 2, 2026
Diana K. Orsini, Sara Di Luch, George Tomlinson et al.
Importance Antidepressant efficacy of intravenous (IV) ketamine has been demonstrated in major depressive disorder; however, the efficacy and safety of ketamine for bipolar depression remain largely unknown, with limited data available in this specific population. Objective To evaluate the efficacy, safety, and tolerability of adjunctive IV ketamine compared with midazolam for...
Journal of Psychiatric Research
June 1, 2026
Kyle Valentino, Hana Ballum, William Cheung et al.
Approximately 80% of individuals diagnosed with major depressive disorder (MDD) report symptoms of insomnia. Glutamatergic modulators, such as ketamine, are reported to be effective for the treatment of depressive symptomatology in adults with MDD. Disrupted glutamate homeostasis is linked to poor sleep quality and sleep disorders. Herein, we sought to systematically determine the effect of...
JAMA Psychiatry
April 15, 2026
Diana Orsini, Sabrina Wong, Sara Di Luch et al.
4 citations
Importance: Psychedelic drugs possess acute psychoactive effects that can compromise blinding integrity in randomized clinical trials (RCTs). Functional unblinding, when participants or raters correctly identify treatment allocation based on subjective effects, may bias outcomes through expectancy effects, challenging the validity of efficacy estimates and regulatory acceptance. Objective: To...
Progress in Neuro-psychopharmacology and Biological Psychiatry
November 22, 2025
Shakila Meshkat, Noah Chisamore, Zoe Doyle et al.
PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect...
Neuroendocrinology
October 30, 2025
Sabrina Wong, Gia Han Le, Jens Uhlig et al.
Our results suggest that NMDAR antagonism improves alpha and beta cell function and viability, which may have translational relevance to comorbid metabolic dysfunction in depression. These mechanisms may subserve the antidepressant effects of select NMDA antagonists (e.g., ketamine/esketamine, dextromethorphan). Further research should aim to investigate the effects of subanesthetic doses of...
The Journal of Clinical Psychiatry
July 7, 2025
Angela T H Kwan, Moiz Lakhani, Joshua D. Rosenblat et al.
2 citations
Background: Ketamine and esketamine have been reported to rapidly alleviate various parameters of suicidality, with antisuicidal effects that may be independent of their rapid-acting antidepressant effects. However, it remains unclear whether ketamine and/or esketamine are associated with the emergence or worsening of suicidality. Methods: In this global observational pharmacovigilance cohort...
Psychiatry Research
May 8, 2025
Noah Chisamore, Lee Phan, Roger S McIntyre et al.
7 citations
Psychedelics have re-emerged as promising treatments for mood disorders. The current model provides a moderate-to-high dose of a psychedelic agent (e.g., psilocybin) to reliably induce an altered state of consciousness. Unfortunately, the hallucinatory effects limit the treatment's potential scalability given patients' vulnerability and extensive monitoring costs, leading to growing interest in...
Acta Psychiatrica Scandinavica
April 16, 2025
Danica E. Johnson, Nelson B. Rodrigues, Rodrigo B. Mansur et al.
Childhood trauma is a well‐established risk factor for major depressive disorder (MDD) and is often associated with attenuated response to conventional antidepressant therapies. Ketamine has emerged as an effective treatment for treatment‐resistant depression (TRD), but the impact of childhood trauma on its effectiveness remains unclear. Herein, we aimed to determine whether childhood trauma...
Journal of Affective Disorders
April 1, 2025
Angela T H Kwan, Moiz Lakhani, Kayla M Teopiz et al.
11 citations
To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine. We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders. Formulations of ketamine and esketamine were evaluated for the...
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2025
Danica E. Johnson, Nelson B Rodrigues, Sydney Weisz et al.
Depression with comorbid posttraumatic stress disorder (PTSD) is associated with more severe symptoms and a reduced response to traditional treatments. Although ketamine shows promise as a rapid-acting antidepressant for treatment-resistant depression (TRD), its effectiveness in patients with comorbid PTSD remains underexplored. Therefore, we conducted a retrospective analysis of 134 patients...
The American journal of psychiatry
2025
Roger S McIntyre, Angela T H Kwan, Rodrigo B. Mansur et al.
23 citations
During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain psychedelics are effective and safe in the treatment of major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder....
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...
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...
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...
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,...
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...
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...
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,...
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...
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...
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....
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...
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...
Journal of Psychopharmacology
May 16, 2023
Noah Chisamore, Kevork Danayan, Nelson B Rodrigues et al.
13 citations
Background: Ketamine is an emerging treatment for treatment-resistant depression (TRD) associated with rapid and robust improvements in depressive symptoms and suicidality. However, the efficacy and safety of ketamine in transitional age youth (TAY; age 18–25) populations remains understudied. Methods: In this retrospective analysis, TAY patients (n = 52) receiving ketamine for TRD were matched...
Psychiatry Research
March 5, 2023
Kevork Danayan, Noah Chisamore, Nelson B Rodrigues et al.
36 citations
Borderline personality disorder (BPD) has high rates of comorbidity with mood disorders, including treatment-resistant depression (TRD). Comorbidity of BPD with depression is associated with poorer response to antidepressants. Intravenous ketamine is a novel treatment for TRD that has not been specifically evaluated in patients with comorbid BPD. In this retrospective analysis of data collected...