International clinical psychopharmacology
September 1, 2023
Mauro Scala, Giuseppe Fanelli, Diana De Ronchi et al.
40 citations
Mood disorders are long-lasting conditions with inconsistent remission rates. Standard antidepressants fail many patients, cause side effects like weight gain and sexual problems, and act slowly. Newer drugs aim to work faster, with fewer side effects, and target symptoms poorly addressed by older medications, such as anhedonia, suicidal thoughts, insomnia, cognitive deficits, and irritability. These agents act on glutamate, GABA, orexin, and other receptors, offering more pharmacodynamic variety to personalize treatment. This review covers the clinical profiles of nine novel compounds—including psilocybin, esmethadone, and zuranolone—to help clinicians weigh benefits and risks for patients with different mood disorder symptoms and comorbidities.
Psychiatry and Clinical Neurosciences Reports
March 1, 2025
Alessandro Serretti
11 citations
Anhedonia, a reduced ability to experience pleasure, is a symptom that cuts across many mental disorders and is linked to poor treatment outcomes. This narrative review surveys interventions that target anhedonia, including medications such as vortioxetine, agomelatine, bupropion, ketamine, and brexpiprazole, which show promising anti-anhedonic effects, while traditional antidepressants like SNRIs and SSRIs are less effective. Neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous auricular vagus nerve stimulation, improve anhedonia when applied to targeted brain areas. Psychotherapeutic approaches such as behavioral activation, mindfulness, and savoring techniques help patients re-engage with pleasurable activities. Emerging treatments like aticaprant and psilocybin also show promise. Improving anhedonia is linked to better psychosocial functioning, quality of life, and sustained remission, supporting routine assessment and tailored intervention strategies.
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.
International clinical psychopharmacology
May 1, 2025
Vincenzo Cardaci, Matteo Carminati, Mattia Tondello et al.
7 citations
Postpartum depression is increasingly recognized as distinct from major depressive disorder, with unique causal factors including hormone fluctuations (estrogen, progesterone, allopregnolone), pathway imbalances (oxytocin, kynurenine), chronobiological factors, and brain imaging alterations. Treatment approaches are expanding beyond traditional antidepressants like sertraline to include newly approved neurosteroids brexanolone and zuranolone, with others under development. Esketamine, psychedelics, brain stimulation, and light therapy also show benefit. Individualized pharmacological and non-pharmacological therapies are being introduced into routine clinical practice.
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
July 14, 2026
Alessandro Serretti
Ketamine and esketamine can relieve depression within hours, even in people who have not responded to other treatments. Yet this advance has not solved the problem of treatment-resistant depression; it has shifted the focus from short-term improvement to what happens afterward. The main unanswered questions are how long the benefit lasts, how to prevent relapse, how to structure and eventually stop maintenance treatment, whether symptom relief leads to functional recovery, which patients benefit most, why useful biomarkers remain unknown, and what the long-term safety and abuse risk of repeated use will be. This review argues that durability, functional recovery, patient selection, long-term safety, and real-world implementation should now guide research and clinical decisions.