Journal of psychopharmacology (Oxford, England)
September 7, 2026
Sabrina Wong, Gia Han Le, Simryn Selby et al.
Extant literature indicates mitochondrial dysfunction may contribute to the pathophysiology of depressive disorders. Preclinical data indicate that anesthetic doses of ketamine are associated with deficits in mitochondrial viability and function. Ketamine and esketamine have demonstrated rapid antidepressant effects in persons with difficult-to-treat depressive disorders. Herein, we aim to...
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...
Expert Opinion on Drug Safety
August 28, 2026
Roger S. McIntyre
1.0 According to the 2023 iteration of the Global Burden of Diseases, Injuries and Risk Factor studies (GBD) assessing 375 injuries and diseases and 12 mental disorders, mental disorders are now th...
August 17, 2026
Tychique T. Wasolua, Morgan S Hardy, Tanner J. Bommersbach et al.
INTRODUCTION: Approximately 30-40% of patients with major depressive disorder fail to respond to conventional antidepressants. Ketamine and esketamine are increasingly used, yet synthesized data on cumulative safety remain limited. This systematic review evaluated long-term safety of both agents. METHODS: MEDLINE, PsycINFO, Embase, and Cochrane Library were searched from inception through...
Journal of Pain and Symptom Management
August 1, 2026
Stefan Aguiar, Mary Makarious, Orly Lipsitz et al.
Depression and existential distress are highly prevalent among patients with advanced cancer, and there is growing evidence for ketamine as a rapidly acting antidepressant in the population, but few studies have examined existential distress outcomes with ketamine treatment. The INKeD-PC trial demonstrated efficacy of intranasal racemic ketamine for depression in patients with cancer receiving...
npj Mental Health Research
July 27, 2026
J. Swainson, P. Grewal, S. Polard et al.
This scoping review maps literature for use of ketamine or esketamine with psychotherapy for depression or depressive symptoms. Forty-seven studies were identified including 4/47 (9%) randomized controlled trials, 4/47 (9%) open label trials, 27/47 (57%) observational or retrospective studies, and 12/47 (26%) individual case reports. Studies were categorized as Ketamine/Esketamine Combined with...
JAMA Psychiatry
July 1, 2026
Sung Ryul Shim, Hye Su Jeong, Tanner J. Bommersbach et al.
1 citation
While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms. To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs). PubMed, PsycInfo, Cochrane Library, and Embase were...
Journal of psychopharmacology (Oxford, England)
June 24, 2026
Shreya Vasudeva, Gabrielle F. M. Lovell, Sabrina Wong et al.
Ketamine has emerged as a promising rapid-acting treatment for mood disorders and suicidality. Notwithstanding its replicated antidepressant efficacy, ketamine-associated risk for abuse, dependence, and misuse remain. We conducted a systematic review of clinical and preclinical studies from database inception to August 2025, including randomized and observational trials, open-label extensions,...
Clinical Neuropharmacology
June 19, 2026
Isabela Heroiu, Gia Han Le, Maria‐christina Sioufi et al.
This systematic review aims to assess the efficacy and tolerability of ketamine in the treatment of obsessive-compulsive disorder. Obsessive-compulsive disorder is a chronic and severe disorder characterized by intrusive thoughts and repetitive behaviours that can cause significant distress. Notwithstanding current treatments and interventions for obsessive-compulsive disorder, some individuals...
Eur Psychiatry
June 16, 2026
A.H. Young, Lucie Bartova, N. Cardoner et al.
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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...
Clinical Pharmacology & Therapeutics
May 28, 2026
Gia Han Le, Sabrina Wong, Danica E. Johnson et al.
Major depressive disorder (MDD) and treatment-resistant depression (TRD) remain leading causes of disability, providing the impetus for receptor-level treatment strategies beyond monoamine reuptake. The serotonin 5-HT2B receptor (5-HT2BR) is uniquely positioned at the interface of central-antidepressant mechanisms and peripheral cardiac risks. Herein, we reviewed preclinical, translational and...
Research Square
May 27, 2026
Tychique T. Wasolua, Tanner J. Bommersbach, Roger S McIntyre et al.
Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review
Journal of Affective Disorders
April 15, 2026
Gia Han Le, Sabrina Wong, Danica E. Johnson et al.
4 citations
Ketamine and esketamine exhibit rapid antidepressant effects in persons with treatment-resistant depression (TRD) and bipolar depression (TRBD). However, the synaptic mechanisms governing dose, frequency, and durability of response remain unclear. This review aims to evaluate the dosing parameters, including minimum dose and optimal dosing intervals, that reliably induce or maintain long-term...
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...
Journal of Affective Disorders
April 1, 2026
Kayla M Teopiz, Gia Han Le, Sabrina Wong et al.
Extant literature suggests that anhedonia, defined as a loss of the ability to feel pleasure or interest, is subserved by dysregulation of reward processing in the central nervous system. Dextromethorphan (DXM), an uncompetitive N-Methyl-d-Aspartate (NMDA) receptor antagonist and sigma-1 (σ1) receptor agonist, is a glutamatergic modulator with antidepressant properties. The effect of DXM on...
CNS Spectrums
March 10, 2026
Halima Faisal, Gia Han Le, Angela T H Kwan et al.
Background: Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants.Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear.We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for...
Psychiatry Research
February 19, 2026
Trisha Menon, Andy Lu, Akhilan Arulmozhi et al.
Ketamine, esketamine, rTMS and ECT are associated with reductions in SI in persons with MDD, with the strongest evidence from randomized controlled trials supporting rapid, short-term effects, particularly for ketamine and esketamine. Further characterization and differentiation of the durability of antisuicidal effects of the aforementioned interventions requires investigation in large-scale,...
Journal of Affective Disorders
February 12, 2026
Erica Kaczmarek, Nelson Rodriguez, Noah Chisamore et al.
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary analysis aimed to evaluate the effects of psilocybin-assisted psychotherapy (PAP) on anhedonia severity in individuals with treatment-resistant depression (TRD). Participants (n = 30) with TRD and a primary diagnosis of Major Depressive Disorder or...
Pharmacopsychiatry
February 5, 2026
Tianyi Xu, Sabrina Wong, Gia Han Le et al.
Serotonergic psychedelics, such as lysergic acid diethylamide, and psilocybin, and the entactogen 3,4-methylenedioxymethamphetamine exhibit agonist activity at the 5-hydroxytryptamine 2B receptor, a signalling pathway known to mechanistically mediate drug-induced valvular heart disease. This systematic review evaluates whether chronic or repeated use of psychedelics and...
Journal of Affective Disorders
February 1, 2026
Kayla M Teopiz, Sabrina Wong, Gia Han Le et al.
Convergent evidence suggests that disrupted reward processing may be associated with observed alterations in frontostriatal activity in persons with major depressive disorder (MDD). Replicated evidence suggests that glutamatergic modulators may benefit persons experiencing disrupted reward function compared to healthy controls (HC). Herein, we systematically reviewed functional magnetic...
Expert Opinion on Therapeutic Targets
January 28, 2026
Gia Han Le, Roger S McIntyre
1 citation
Up to 50% of adults with major depressive disorder (MDD) fail to achieve remission after two or more monoaminergic antidepressants and meet criteria for treatment-resistant depression (TRD). Low-dose intravenous ketamine, intranasal esketamine, and oral dextromethorphan represent the first glutamatergic treatments to exhibit rapid and robust efficacy in persons with TRD, yet their precise...
European Psychiatry
2026
Andy Lu, Heidi Xu, Gia Han Le et al.
4 citations
The reported mixed findings suggest that the opioid system may exert a partial mediating effect of ketamine in TRD. However, given the inconsistent attenuation of ketamine's antidepressant effects by opioid receptor antagonists, the opioid system likely functions as a context-dependent modulator rather than a primary mediator, particularly at standard antidepressant doses.
Therapeutic Advances in Psychopharmacology
2026
Alessandro Cuomo, Roger S McIntyre, Despoina Koukouna et al.
1 citation
Treatment-resistant depression (TRD) remains a major clinical challenge, and long-term real-world data on intranasal esketamine are limited. To describe long-term dosing patterns and clinical outcomes associated with intranasal esketamine in routine clinical practice. Single-center observational cohort study with descriptive analyses. We analyzed 45 patients with TRD treated with intranasal...
General Hospital Psychiatry
2026
Gabrielle F. M. Lovell, Shreya Vasudeva, Diana Orsini et al.
Ketamine is a dissociative anesthetic with potential for treating mood, anxiety, and related disorders; however, concerns have emerged regarding hepatotoxicity in the context of chronic treatment. Systematic searches of PubMed, Scopus, and Ovid databases were conducted from inception to August 2025. Eligible studies included randomized controlled trials (RCTs), observational studies, and case...