Expert Opinion on Drug Metabolism & Toxicology
2026
Yang Jing Zheng, Christine E. Dri, Sabrina Wong et al.
Dextromethorphan/Buproprion (DXM/BUP) has received breakthrough FDA approval in August 2022 as a rapid-acting antidepressant. DXM/BUP is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, with bupropion (BUP), a norepinephrine/dopamine reuptake inhibitor and cytochrome P450 2D6 (CYP2D6) inhibitor. As DXM/BUP moves closer to widespread clinical use for...
Acta Psychiatrica Scandinavica
December 1, 2025
Liyang Yin, A. Imamog ̄lu, Gia Han Le et al.
3 citations
ABSTRACT Introduction Posttraumatic stress disorder (PTSD) is a mental disorder resulting from exposure to traumatic events. Evidence suggests that ketamine may be efficacious in treating PTSD, however, ketamine's mechanisms in treating PTSD remain unclear. Herein, this review aims to evaluate the clinical outcomes of ketamine treatment in persons with PTSD and investigate the possible...
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...
Journal of Psychiatric Research
October 30, 2025
Isabella S Ji, Morgan C H Cheng, Kayla M Teopiz et al.
2 citations
INTRODUCTION: Functional impairment is commonly reported amongst individuals with major depressive disorder (MDD) or treatment-resistant depression (TRD). Extant evidence suggests that ketamine and esketamine, N-methyl-D-aspartate (NMDA) receptor antagonists and glutamatergic modulators, have shown efficacy in treating MDD/TRD. While symptom reduction remains central to treatment, many...
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...
Can J Psychiatry
October 28, 2025
Jennifer Swainson, Elisa Brietzke, Atul Khullar et al.
2 citations
There has been a renewed interest in the use of various psychedelic agents as potential therapies for multiple psychiatric conditions, including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), to name a few. This follows the recent accumulation of evidence for ketamine pharmacotherapy and a rapid proliferation of clinics/programs...
Journal of Affective Disorders
September 16, 2025
Sami George Sabbah, Sophie Li, Sabrina Wong et al.
2 citations
Although these findings suggest psilocybin is associated with dynamic and temporally distinct neuroplastic changes linked to clinical improvement, several limitations must be acknowledged. Many studies reused overlapping datasets with high exploratory flexibility and risk of bias. The generalizability of results is therefore constrained. Future research should emphasize independent datasets,...
Psychiatry Research
August 15, 2025
Sipan Haikazian, Roger S McIntyre, Shakila Meshkat et al.
7 citations
Antidepressant effects with sub-anesthetic doses of intravenous ketamine have been previously demonstrated. However, previous studies have primarily evaluated the efficacy of acute treatment protocols, with limited research on maintenance treatment. Moreover, controlled maintenance studies have only included patients with treatment-resistant Major Depressive Disorder (TRD), with no maintenance...
CNS Spectrums
August 12, 2025
Gia Han Le, Sabrina Wong, Stavroula Bargiota et al.
3 citations
G protein-coupled receptors (GPCRs) are involved in many physiological and pathophysiological processes. Conventional pharmacological models categorize the typology of pharmacologic ligands as agonists or antagonists. Biased agonism is a relatively newer pharmacodynamic characteristic that has potential to optimize therapeutic efficacy while minimizing adverse effects in psychiatric and...
Journal of Affective Disorders
August 1, 2025
Morgan C H Cheng, Christine E. Dri, Hana Ballum et al.
12 citations
The rapid and clinically meaningful antidepressant effects of ketamine and esketamine are well-established in major depressive disorder (MDD) and treatment-resistant depression (TRD) as evidenced by improvement in clinician- and patient-reported depression measures. However, there remains a need to determine how these agents affect patient-reported quality of life (QoL). Herein, we aimed to...
The American journal of geriatric psychiatry
August 1, 2025
Ronesh Sukhdeo, Jocelyn K. Tamura, Christine E. Dri et al.
Ketamine has emerged as a promising treatment for major depression, though its efficacy and safety remain incompletely characterized in older adults. This systematic review synthesizes current evidence for ketamine in geriatric depression. A search of PubMed, EMBASE, and PsycINFO was conducted. Prospective clinical trials were included, with age restriction to participants ≥60 years applied at...
Psychiatry Research
July 26, 2025
Giacomo D’andrea, Clara Cavallotto, Mauro Pettorruso et al.
16 citations
INTRODUCTION Anhedonia, defined as the diminished ability to experience or anticipate pleasure, is a core symptom of major depressive disorder (MDD) and bipolar depression (BD), and associated with depression severity, suicidality and poor treatment outcomes. Conventional antidepressants demonstrate limited efficacy against anhedonia. Esketamine nasal spray (ESK-NS) - a novel NMDA receptor...
Journal of Affective Disorders
July 23, 2025
Joyce Xu Hao Jin, Heidi Ka Ying Lo, Iris Wai Tung Tsui et al.
2 citations
Holistic management of persons living with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) invites the need for evaluation of positive mental health (PMH; pleasure attainment and meaning-in-life), alongside conventional measures of psychopathology. The aforementioned dimensions of PMH involve aspects of mindfulness and grit. Herein, we evaluate these aspects using ecological momentary...
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...
Journal of Psychopharmacology
July 1, 2025
Ryan M Brudner, Erica Kaczmarek, Marc G Blainey et al.
3 citations
Background: Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects...
Expert Opinion on Therapeutic Targets
June 1, 2025
Naomi Xiao, Liyang Yin, Kayla M Teopiz et al.
5 citations
The mechanism of action of antidepressants is not fully ascertained. In addition to monoamines, disparate other effectors are also implicated in the molecular and cellular effects of chronic stress including neurogenesis, neurodifferentiation, and neuroplasticity. Evidence suggests sigma-1 receptors (S1Rs) as a putative target and possible mediator of antidepressant activity. Data from...
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...
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
April 1, 2025
Eduard Vieta, Nahida Ahmed, Celso Arango et al.
12 citations
Patients with treatment resistant depression (TRD) experience a greater negative impact on their functioning and productivity at home and in the workplace versus treatment-responsive patients. Here, we report the effects of esketamine nasal spray (NS) versus quetiapine extended release (XR) on functioning, work productivity and activity impairment. ESCAPE‑TRD (NCT04338321) was a 32-week...
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...
The Canadian Journal of Psychiatry
March 25, 2025
Noah Chisamore, Erica Kaczmarek, Zoe Doyle et al.
1 citation
Objective: To compare changes in depression, anxiety, and suicidality symptoms after a single 25 mg oral dose of psilocybin between treatment-resistant depression participants not on antidepressants at screening to participants that discontinued antidepressant medications leading up to receiving psilocybin-assisted psychotherapy (PAP). Methods: Participants (n = 27) received at least one 25 mg...
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...
Pharmaceuticals (Basel, Switzerland)
January 24, 2025
John E Donello, Roger S McIntyre, Donald B Pickel et al.
14 citations
Plastogens are a class of therapeutics that function by rapidly promoting changes in neuroplasticity. A notable example, ketamine, is receiving great attention due to its combined rapid and long-term antidepressant effects. Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist, and, in addition to its therapeutic activity, it is associated with psychotomimetic and dissociative side...
CNS Spectrums
January 17, 2025
Roger S McIntyre, Gregory W Mattingly, Yordan Godinov et al.
9 citations
Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and...
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....