Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
May 31, 2024
Alessandro Serretti
8 citations
After many decades, many new antidepressants have been approved and more are in development, offering faster action, better tolerability, and broader treatable disorders. Neurosteroids provide rapid benefits for postpartum, anxious, and bipolar depression. Dextromethorphan and bupropion combination may help major and treatment-resistant depression. Dextromethadone may augment partial antidepressant response. Psychedelic drugs can produce long-lasting benefits after a single administration but remain experimental. Botulinum also offers single-administration antidepressant effects lasting weeks or more. Other promising mechanisms include new drug targets, drug repurposing, and genetic or epigenetic manipulations. Clinicians need updated evidence to translate new findings into practice.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
November 30, 2025
Xiayun Wan, Akifumi Eguchi, Rumi Murayama et al.
5 citations
Intermittent doses of MDMA (10 mg/kg three times per week for six weeks) increased whole-body and femoral bone mineral density in ovariectomized mice, compared with vehicle. The treatment shifted bone-remodeling markers toward an antiresorptive profile—lower RANKL and higher osteoprotegerin. Gut microbiota profiling showed reduced Clostridia and enriched Bacilli, and untargeted metabolomics revealed a marked decrease in plasma β-D-allose, a metabolite linked to Lactobacillus johnsonii. These findings suggest that intermittent MDMA may mitigate bone density loss after ovariectomy, potentially through remodeling of a gut microbiota–bone axis. Causal microbial and metabolic mediators remain to be defined.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
November 30, 2025
Alessandro Serretti
2 citations
Depression is increasingly seen as a disorder of impaired synaptic plasticity and excitation-inhibition imbalance in brain circuits. Two rapid-acting drug classes—NMDA receptor modulators (ketamine, esketamine) and neuroactive-steroid GABA-A positive allosteric modulators (brexanolone, zuranolone)—offer complementary approaches to restore circuit function. Intravenous ketamine and intranasal esketamine outperform placebo and active comparators in treatment-resistant depression, with esketamine approved in the US as adjunctive and monotherapy. Both reduce suicidal ideation within hours to days, though effects on suicidal behavior are not demonstrated. Safety concerns include dissociation, hemodynamic changes, and with prolonged exposure, cystitis and misuse liability. Neurosteroid GABA-A modulators are effective in postpartum depression, with preliminary evidence in major depression; adverse events are mainly dose-dependent sedation. Brexanolone requires monitored infusion; zuranolone enables a 14-day outpatient course. Robust efficacy predictors remain limited.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
August 31, 2024
Juthawadee Lortrakul, Keerati Pattanaseri
1 citation
Ketamine therapy can reduce suicide risk and depression in treatment-resistant patients, but its adverse effects include blurred vision, nausea, hepatotoxicity, headache, and cystitis. The effect on blood glucose is unclear. A 36-year-old man with type 1 diabetes mellitus experienced recurrent hypoglycemia episodes after ketamine infusion for treatment-resistant depression, despite no severe hypoglycemia in the prior 20 years. His depression improved with ketamine, but clinicians should monitor for hypoglycemia when initiating ketamine infusion in patients with type 1 diabetes.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
May 31, 2026
Yong Yue, Yi Cai, Rumi Murayama et al.
Gut bacteria contribute to baseline central oxytocin signaling in rats, but are not necessary for the acute oxytocin release triggered by MDMA. Male rats given broad-spectrum antibiotics for seven days showed enlarged ceca, confirming microbiome disruption, yet maintained stable body weight. Baseline oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus was significantly reduced after antibiotic treatment, while peripheral oxytocin levels remained unchanged. MDMA administration increased central oxytocin expression similarly in both antibiotic-treated and control rats, and MDMA-induced peripheral oxytocin levels also did not differ between groups. The findings indicate that gut microbiota help maintain central oxytocin under normal conditions but are not required for MDMA's oxytocin-activating effects.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
August 31, 2025
Cagdas Türkmen, Rutger Boesjes, Anne-Fleur Zandbergen et al.
In adults with treatment-resistant depression, intranasal esketamine added to an antidepressant does not change the likelihood of experiencing insomnia as a side effect compared with placebo. Across seven randomized trials involving 1,311 patients, insomnia was reported by 7.3% of those receiving esketamine and 6.7% of those receiving placebo, a difference that was not statistically significant. This finding contrasts with earlier reports that esketamine improves insomnia symptoms, possibly because adverse-event reporting does not capture gradual improvements in sleep for patients who often have insomnia at the start of treatment.