The International Journal of Neuropsychopharmacology
September 9, 2026
C Zarate
Abstract Background Ketamine produces rapid antidepressant and anti-anhedonic effects in treatment-resistant depression, but response is heterogeneous and mechanisms at the circuit level remain incompletely defined. Convergent imaging work implicates anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and reward-related networks as key loci for ketamine’s therapeutic and...
The International Journal of Neuropsychopharmacology
September 9, 2026
Mario F Juruena
Abstract Background Ketamine has rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD), but optimal implementation, route selection, and longer-term maintenance strategies remain areas of active clinical development. At the Maudsley Advanced Treatment Service (MATS), ketamine and esketamine are delivered within a specialist governance framework, using multiple...
The International Journal of Neuropsychopharmacology
September 9, 2026
Mostafa El Mansari, Naomichi Okamoto, Pierre Blier
Abstract Background Low-dose racemic ketamine enhances the firing rate and burst activity of rat norepinephrine neurons in the locus coeruleus, as well as the population activity of dopamine neurons in the ventral tegmental area [El Iskandrani et al, 2015]. These brainstem monoamine nuclei densely innervate the prefrontal cortex (PFC), whereas clinical studies have shown a facilitation of...
The International Journal of Neuropsychopharmacology
September 9, 2026
Claudio Agnorelli, Joseph Peill, Danielle Kurtin et al.
Abstract Background Clinical studies have shown that ketamine and classic psychedelics can produce robust and rapid antidepressant effects after a single or a few administrations. However, the neurobiological mechanisms driving these long-lasting changes remain unclear. A leading framework proposes that both drug classes induce sustained increases in neuroplasticity, potentially reshaping...
The International Journal of Neuropsychopharmacology
September 9, 2026
A Solomon, Y Domany
Abstract Background A critical gap exists in understanding the biological mechanism linking ketamine’s rapid anti-suicidal effects to the Interpersonal Theory of Suicide (IPTS). While the "Kinetic Mismatch" between acute relief and delayed synaptogenesis is well-known, current models overlook how ketamine modulates “Thwarted Belongingness” (a core IPTS pillar) and the attachment anxiety that...
bioRxiv (Cold Spring Harbor Laboratory)
September 8, 2026
Tomokazu Tsurugizawa, Aya Takemura
preprint
A single injection of a subanesthetic dose of ketamine, an NMDA receptor antagonist, induces schizophrenia-like behavior in mice. Previous studies investigated the effect of single injection of ketamine on behavior and c-Fos expression in mice dose-dependently. However, there has not been functional magnetic resonance imaging (fMRI) study to investigate the effect of ketamine in mice. Here, we...
Journal of Psychiatric Research
September 7, 2026
Objective: Treatment-resistant depression (TRD) is associated with severe functional impairment, poor quality of life, and increased suicide risk. This study evaluated the effectiveness of intranasal esketamine on depressive symptoms, hopelessness, suicidal ideation, and quality of life in patients with TRD, exploring whether outcomes differed according to concomitant antidepressant class (SSRI...
Research Square
September 7, 2026
Jennifer L Phillips, Ifeoluwa Olaoluwa, Areebah Ahmed et al.
preprint
Abstract Metabolic, inflammatory, and neurotrophic measures may provide complementary insight into biological heterogeneity underlying treatment-resistant depression and response to ketamine-based treatments. However, biomarker studies of ketamine treatment have focused on individual markers or biological domains, most commonly inflammatory or neurotrophic, while metabolic measures remain...
Journal of Psychopharmacology
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...
bioRxiv (Cold Spring Harbor Laboratory)
September 6, 2026
Adam Dawoud, Achla Gupta, Ivone Gomes et al.
preprint
Opioid Use Disorder (OUD) continues to be a pressing public health crisis, marked by high relapse rates and limited treatment options. Ketamine, a non-competitive N-Methyl-D-Aspartate receptor (NMDAR) antagonist, has emerged as a promising therapeutic for numerous psychiatric illnesses due to its robust antidepressant properties and glutamate-mediated synaptic plasticity. However, ketamine's...
The World Journal of Biological Psychiatry
September 6, 2026
Balwinder Singh, Siamak MahmoudianDehkordi, Jennifer L. Vande Voort et al.
OBJECTIVE: Ketamine is a rapid-acting antidepressant with an incompletely understood mechanism of action. Pharmacometabolomics can identify pathways underlying its effects and response variability. Using data from the Bio-K trial (NCT03156504), a multisite open-label study, we characterised metabolomic signatures of intravenous (IV) racemic ketamine in adults with treatment-resistant depression...
Annals of Palliative Medicine
September 3, 2026
Danielle B Tometich, Christina L Hersh, Matthew A Murphy et al.
Background: Given the growing population of patients living with metastatic cancer, palliative care providers need every available tool for symptom management. We conducted a rapid review of the literature on palliative uses of ketamine for pain and depression in people with cancer. Methods: We systematically searched for studies published since 2015 that examined palliative uses of ketamine in...
Frontiers in Psychiatry
September 3, 2026
Anita Słupska, Wiesław Jerzy Cubała, Damian Swieczkowski et al.
Objectives Ketamine and esketamine are increasingly used for treatment-resistant depressive disorders, particularly when rapid symptom reduction is clinically desirable. Intranasal esketamine has a product-specific regulatory framework in several jurisdictions, whereas most racemic ketamine formulations remain off-label for psychiatric indications. This narrative review provides practical...
Frontiers in Psychiatry
September 3, 2026
Mary R. Shen, Kwadwo Owusu-Boaitey, Zackari D. Murphy et al.
IntroductionOpioid use disorder (OUD) remains a major public health crisis despite evidence-based medications, including methadone, buprenorphine, and naltrexone. Persistent challenges with treatment retention, access, stigma, and incomplete response highlight the need for adjunctive pharmacotherapies targeting neurobiological systems beyond the mu-opioid receptor.MethodsWe conducted a...
Molecular Psychiatry
September 2, 2026
Yunkai Sun, Yehong Fang, Pu Peng et al.
Marked interindividual heterogeneity in substance use disorder (SUD) impedes the identification of consistent neuroanatomical alterations, limiting the development of robust markers for clinical risk stratification. We applied a normative modeling framework to explore individual neuroanatomical deviations in individuals with SUD across two distinct substance classes, and assessed their...
medRxiv
September 2, 2026
Yingqian Zhang, Xiaoman Zhuang, Mengqi Niu et al.
preprint
Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It’s characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and...
JAMA Psychiatry
September 2, 2026
Diana 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...
Drug safety
September 2, 2026
You Wang, Alexandra S Storaci, G Caleb Alexander et al.
Treatment-resistant depression (TRD) is associated with elevated suicide risk, but real-world evidence on whether esketamine reduces suicide attempts and intentional self-harm remains limited. The aim was to estimate whether current esketamine exposure was associated with a higher or lower risk of recorded nonfatal, medically attended suicide attempt or intentional self-harm among adults with...
Indian Journal of Psychiatry
September 1, 2026
Anand Prakash, Pranab Mahapatra, Jigyansa I. Pattnaik et al.
ABSTRACT Background: The 4–12 week lag period of conventional antidepressants creates critical vulnerability in severe depression, with peak suicide risk during the first month. While ketamine research has focused on treatment-resistant populations, its potential to eliminate this lag period in non-treatment-resistant severe depression remains unexplored. Aims: To evaluate whether add-on...
The Journal of Clinical Pharmacology
September 1, 2026
Neil McNaughton, Ben Beaglehole, Paul Glue
The dose-response profile of racemic ketamine in internalizing disorders is poorly characterized. This was a secondary analysis of outcome responses in patients with treatment-resistant depression, post-traumatic stress disorder, generalized and/or social anxiety, or obsessive-compulsive disorder. For each disorder, they received single intramuscular doses of racemic ketamine (0.5 and 1.0...