We report the case of a 24-year-old woman suffering from severe depersonalization/derealization disorder (DPDR), characterized by profound emotional numbness, feelings of unreality toward herself and her environment, and persistent suicidal ideation. Despite multiple pharmacological interventions – including antidepressants, antipsychotics, and repetitive transcranial magnetic stimulation – her...
Depression is a common, debilitating, and potentially life-threatening mental disorder affecting individuals across all age groups and populations. It represents one of the major challenges of contemporary medicine. It is estimated that more than 300 million people worldwide are affected, and patients with major depressive disorder (MDD) exhibit a significantly increased risk of suicide,...
Treatment-resistant depression (TRD) remains a significant public-health challenge, with many patients failing to respond to conventional therapies. Ketamine has emerged as a rapid-acting intervention, but quantitative outcomes alone do not capture patients' lived experiences, which shape engagement, acceptability, and adherence. We conducted a narrative review of qualitative and mixed-methods...
Ketamine’s development in psychiatry exemplifies the evolution of psychopharmacology over six decades. Originally introduced as a dissociative anesthetic and psychotomimetic probe, ketamine has been repositioned as a rapidly acting antidepressant, particularly for treatment-resistant depression (TRD). This narrative review draws on historical sources, clinical trials, regulatory documents, and...
Treatment-resistant depression (TRD) is a complex and heterogeneous condition affecting a considerable subset of patients who do not respond to conventional antidepressants. Given the limitations of traditional treatment strategies, there is a growing need for alternative and personalized approaches. This review explores the neurobiological underpinnings of TRD and examines the efficacy of...
ABSTRACT: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been approved for use as a clinical and veterinary anesthetic since 1970. Although esketamine, a specific molecular form of ketamine, is FDA-approved for the management of treatment-resistant depression, regular ketamine is often used off-label at subanesthetic doses to treat depression as well as other...
Postoperative nausea and vomiting (PONV) are common complications after surgery. Opioid use is a significant risk factor. We utilised a crossover design to test this hypothesis in the same individuals that opioid-free anaesthesia (OFA) compared with opioid-inclusive anaesthesia reduces PONV. This randomised double-blind crossover trial included adult patients undergoing two surgical procedures...
Depression is increasingly conceptualized as a disorder of impaired synaptic plasticity and excitation-inhibition imbalance within corticolimbic circuits. Two rapid-acting therapeutic classes, NMDA receptor modulators (ketamine, esketamine) and neuroactive-steroid GABA-A positive allosteric modulators (brexanolone, zuranolone), offer complementary approaches to restore circuit function....
PsychopharmacologyNovember 5, 2025Milad Soltanzadeh, Wang Zheng, Shona G. Allohverdi et al.1 citation
RationaleKetamine and psilocybin have demonstrated therapeutic potential for mental disorders, including major depressive disorder, yet they engage distinct mechanisms of action. Ketamine, a dissociative hallucinogen, acts by blocking N-methyl-D-aspartate receptors (NMDAR), whereas psilocybin primarily targets serotonin receptors. These divergent mechanisms are reflected in their...
Background: Treatment-resistant depression (TRD) affects up to a third of patients with major depressive disorder and remains difficult to manage with conventional therapies. Rapid-acting antidepressants targeting the glutamatergic system, such as ketamine, esketamine, and dextromethorphan-bupropion, have emerged as promising alternatives. Nitrous oxide, also an NMDA receptor antagonist, has...