Expert Opinion on Pharmacotherapy
November 10, 2023
Michail Kalfas, Rosie H Taylor, Dimosthenis Tsapekos et al.
28 citations
Psychedelic therapy is transforming treatment for treatment-resistant depression (TRD) by increasing benefits and reducing risks. Psilocybin shows promise as a potential game-changer, with initial evidence indicating a rapid antidepressant effect that lasts at least three months for some responders. However, more rigorous, double-blind, comparator-controlled trials with adequate statistical power are needed to understand how psychedelics work and their long-term effects in TRD. Psychedelics may also benefit other psychiatric conditions like bipolar depression and post-traumatic stress disorder.
Expert Opinion on Pharmacotherapy
December 1, 2024
Millie C Kirchberg, Claire Pinson, Guido K W Frank
9 citations
Anorexia nervosa has one of the highest mortality rates among mental illnesses, yet no approved pharmacological treatments exist. This narrative review examines traditional pharmacotherapy and novel treatments—including dissociative anesthetics, psychedelics, cannabinoids, hormones, neurosteroids, and ketogenic nutrition—for altering neurobiology and behavior. The authors recommend a neuroscience-based medication approach targeting dopamine receptors to enhance cognitive flexibility and reduce food-related dread when psychotherapy fails. Treating comorbid anxiety, depression, and obsessive-compulsive disorder is essential, as these conditions persist even after successful anorexia treatment. Novel strategies show promise for improving mood and reducing specific anorexia psychopathology and may soon enter clinical practice.
Expert Opinion on Pharmacotherapy
March 1, 2024
Georgios D Kotzalidis, Federica Fiaschè, Alessandro Alcibiade et al.
3 citations
Suicidal behavior is common among people with bipolar disorder and is the leading cause of death in this group, with rates remaining high despite standard treatments like lithium, antidepressants, and psychotherapy. A review of PubMed identified few studies on acute suicidality and lithium or clozapine, but 14 studies on ketamine, esketamine, or glutamate-related treatments. Glutamatergic abnormalities are present in both bipolar disorder and suicide. The NMDA antagonist ketamine and its S-enantiomer esketamine appear to decrease acute suicidality, possibly by rapidly remodeling glutamate activity. Intranasal esketamine or subcutaneous ketamine, and possibly other glutamate receptor modulators, may improve suicidal behavior in unipolar and bipolar depression, suggesting glutamatergic modulators could reduce acute suicidality and mortality in bipolar disorder.
Expert Opinion on Pharmacotherapy
March 24, 2026
Donatella Marazziti, Matteo Gambini, Riccardo Gurrieri et al.
After decades of limited use, psychedelic compounds are reemerging as potential treatments for mental disorders that do not respond to existing therapies. This narrative review examines the current clinical and regulatory landscape of psychedelic-assisted therapies, covering ketamine, esketamine, MDMA, psilocybin, LSD, DMT, 5-MeO-DMT, and ibogaine for conditions like major depressive disorder, PTSD, and substance use disorders. The authors argue that these therapies will not follow standard prescription models but require specialist-delivered, psychotherapy-integrated care. Late-stage trials show promise for high-need populations, but unresolved challenges around long-term safety, scalability, workforce training, equity of access, and legal accountability remain.
Expert Opinion on Pharmacotherapy
February 1, 2026
Alessandro Cuomo, Mario Pinzi, Andrea Fagiolini
Major depressive disorder remains a leading cause of disability globally. Many patients do not respond adequately to traditional antidepressants. This review examines phase 3 clinical trial evidence for newer agents, including brexanolone, intranasal esketamine, dextromethorphan-bupropion, vortioxetine, and glucagon-like peptide-1 receptor agonists. These treatments offer rapid symptom relief and potential cognitive or metabolic benefits for conditions like postpartum depression, acute suicidal ideation, and treatment-resistant depression. However, limited integration into clinical guidelines, insufficient long-term data, and implementation barriers restrict their use. The authors call for clearer treatment sequencing strategies and harmonized recommendations to support more individualized depression management.
Expert Opinion on Pharmacotherapy
January 22, 2026
Diana Orsini, Sara Di Luch, Gabrielle F. M. Lovell et al.
A large body of evidence from clinical trials and real-world studies supports the antidepressant effects of intravenous ketamine and intranasal esketamine. Larger studies have provided reassuring safety data, including for long-term treatment. Alternative routes of administration show promise for scalability, but their efficacy relative to intravenous ketamine remains unclear. Preliminary data suggest ketamine may also be effective for bipolar disorders, personality disorders, posttraumatic stress, and obsessive-compulsive disorder. Further research is needed to optimize protocols, such as combining ketamine with other interventions. Challenges include functional unblinding, expectancy-related bias, and treatment costs.
Expert Opinion on Pharmacotherapy
February 1, 2025
Alejandra Pulido-Saavedra, Anna Borelli, Razi Kitaneh et al.
Substance use disorders remain a public health challenge; few have FDA-approved treatments, and those that do suffer from high dropout rates. This narrative review examined clinical evidence for non-psychedelic medications that primarily target the 5-HT2A receptor. Results on craving and abstinence were mixed, with some positive effects but no consistent pattern. Comparing these findings with those for psychedelic agents (which are typically 5-HT2A agonists) suggests that mixed results are not unique to non-psychedelics. Because most non-psychedelic agents reviewed are 5-HT2A antagonists, while psychedelic agonists show more uniformly positive outcomes, the authors propose that 5-HT2A receptor agonists are a promising avenue for treating substance use disorders, possibly by addressing a common underlying chronic hypodopaminergic state.