In patients with treatment-resistant depression (TRD), the efficacy and tolerance of intranasal esketamine (ESK) spray, alone or combined with oral antidepressants, has been supported by clinical trials and observational studies. The French real-world ESKALE study assessed the benefit of ESK in 157 patients with TRD. In this post-hoc analysis of the ESKALE study we aimed to describe the...
Ketamine consists of two enantiomers, (R)-ketamine and (S)-ketamine, which exhibit distinct pharmacological properties. Currently, only the (S)-enantiomer has been approved for the treatment of major depressive disorder, whereas recent clinical studies have failed to demonstrate an antidepressant effect for (R)-ketamine. The quantitative electroencephalography (qEEG) gamma-enhancing effect of...
Accumulating evidence suggests that the opioid system may modulate ketamine's rapid antidepressant effects. The objective of this study was to test whether opioid system modulation via naltrexone alters ketamine's acute effects on regional cerebral blood flow (rCBF) in major depressive disorder (MDD), and whether these changes relate to symptom measures and map onto receptor density profiles....
Suicide is a major global health problem. Growing evidence shows that immune dysregulation and inflammation contribute to suicidality. This review summarises inflammatory mechanisms associated with suicidal behaviour and evaluates emerging therapeutic strategies targeting these pathways. A narrative literature review was conducted using a combination of keywords, including suicide, therapy,...
Aims: To review and compare the safety, efficacy, cost-effectiveness and remission rates of electroconvulsive therapy (ECT) versus ketamine in patients with major depressive episodes. Methods: A narrative review of the literature was undertaken, focusing on randomised and non-randomised clinical trials, systematic reviews, and meta-analyses comparing ketamine and ECT in adults with major...
Les troubles liés à l’usage de substances (TUS) touchent environ 2 % de la population mondiale et sont associés à une morbidité importante ainsi qu’à un risque de rechute élevé. Les envies impérieuses (le craving), définies comme une envie intense de consommer une substance, constituent une caractéristique centrale et transdiagnostique des TUS et représentent un prédicteur clé de rechute. Les...
BJPsych OpenJune 1, 2026Imtiaz Ahmad Dogar, Palvisha Sajid, Dua Fatima et al.
Aims: In the light of limited relevant local literature, we planned our research to build a scientific database related to the immediate and sustained effects of this innovative treatment modality at our tertiary care hospital, in order to start ketamine clinic in our department . We didn’t find any research in Faisalabad, Pakistan on the subject, ensuring a more in depth understanding of the...
Suicidal ideation and deliberate self-harm are frequent and persistent in treatment-resistant depression (TRD), particularly when comorbid borderline personality disorder (BPD) is present. Real-world evidence on antisuicidal outcomes during intranasal esketamine in this population remains limited. In this multicentre prospective observational study, 90 outpatients with TRD received intranasal...
The Journal of PhysiologyJune 1, 2026Felipe Guiffa-Gómez, Sashá Van Buuren, Freddy Aguilar et al.1 citation
The medial prefrontal cortex (mPFC) undergoes extensive GABAergic interneuron maturation during adolescence, a process that establishes excitatory-inhibitory balance and supports adult cognitive function. Disruptions during this critical developmental period contribute to neuropsychiatric disorders, yet the enduring consequences for adult synaptic plasticity remain poorly understood. Here we...
Asian Journal of PsychiatryJune 1, 2026Hariprasad Ganapathy Vijayakumar, Varsha Shamanna, Harsh Pathak et al.1 citation
Treatment resistance in bipolar depression is one of the most challenging clinical conditions to treat in psychiatry. We present a case of an elderly gentleman with chronic Multi-Therapy Resistant Bipolar Depression (MTRBD), where ketamine, a preferential NMDAR blocker on cortical GABAergic interneurons, is used adjunctively with sequential theta burst stimulation (sTBS) to achieve remission....
Ketamine rapidly reduces suicidal ideation in major depressive disorder (MDD), but its effects are transient. Preclinical and clinical studies suggest that ketamine's antidepressant and antisuicidal effects may be partly mediated by mu-opioid receptor (MOR) modulation. The authors investigated the efficacy and safety of low-dose sublingual buprenorphine, a partial MOR agonist, as a follow-on...
Suicide is a major cause of death worldwide and a key public health challenge. Pharmacologic and neuromodulatory interventions are central to suicide prevention. This review summarizes evidence for these interventions with potential antisuicidal effects across major psychiatric disorders and, where possible, distinguishes their direct effects on suicide diathesis from those mediated by...
NeuropharmacologyJune 1, 2026Nehal G. Fahmy, Nada M. Kamel, Mahmoud M. Khattab et al.
Doxorubicin (DOX), a widely utilized chemotherapeutic agent, is associated with significant adverse effects, including cognitive dysfunction (chemobrain) and depression. Ketamine (KET), the anesthetic, was off-label used as antidepressant and got FDA approval in 2019 for treatment-resistant depression management. Hence, this study investigated the therapeutic efficacy of single [KET(S)] versus...
Ketamine exerts rapid antidepressant effects. However, currently available ketamine-based treatments are associated with dissociative and cardiovascular adverse effects. To evaluate the antidepressant efficacy and tolerability of KET01, a novel, oral, prolonged-release racemic ketamine tablet formulation. KET01-03 was an active-comparator, double-blind, double-dummy, crossover phase 1...
Major depressive disorder remains a leading cause of disability, and decades of monoamine-centered pharmacology have yielded delayed and often incomplete relief. Rapid-acting antidepressants reshaped the field by linking swift symptom improvement to glutamatergic plasticity, yet durable benefit depends on how newly reconfigured circuits are stabilized and tuned. This review synthesizes evidence...
Ketamine is increasingly used in clinical settings for mental health and pain management, yet its misuse poses public health risks. While prior studies have examined ketamine trends, few have explored its use among individuals receiving treatment for substance use disorders (SUD). Using 2021-2023 data from the National Survey on Drug Use and Health (NSDUH), we analyzed the association between...
PharmaceuticalsMay 31, 2026Wenting Zhang, Xin Guo, Jiping Zhang et al.
Background: Ketamine is a rapid-acting antidepressant for major depressive disorder; however, its effects are short-lasting and associated with neurotoxic side effects. Thus, identifying strategies to prolong its antidepressant effects is of critical importance. It has been shown that Dajianzhong Decoction (DJZT) prolongs the antidepressant effects of ketamine through modulation of the gut...
Background Ketamine has emerged as an effective rapid-acting treatment for treatment-resistant depression (TRD), producing significant antidepressant effects within hours of administration. Given ketamine’s capacity to induce states of heightened neuroplasticity and psychological openness, psychotherapy may represent a meaningful complement to its pharmacological effects — facilitating...
Oral ketamine has gained increasing interest beyond anesthesia, particularly for treatment-resistant depression, chronic pain, and pediatric procedural sedation. Despite expanding off-label use, there is no standardized pharmaceutical formulation, and long-term safety remains uncertain. A synthesis of evidence on safety and tolerability of the oral route is therefore needed to inform clinical...
Depression is a common and serious concern in cancer patients, significantly impacting quality of life, treatment adherence, and overall prognosis. While traditional antidepressants often take weeks to exert therapeutic effects, ketamine has emerged as a potential alternative due to its rapid antidepressant action. This systematic review explores the efficacy, safety, and clinical role of...