Frontiers in psychiatry
January 1, 2021
Georgios Mikellides, Panayiota Michael, Lilia Psalta et al.
17 citations
Both intramuscular ketamine and repetitive transcranial magnetic stimulation (rTMS) effectively reduced depressive and anxiety symptoms in patients with treatment-resistant depression. In a naturalistic clinical setting, 24 patients received either eight sessions of ketamine or 30 sessions of left dorsolateral prefrontal cortex intermittent theta-burst stimulation. Both groups showed significant improvement from pre- to post-treatment on three clinical assessments, with no significant differences between the therapies in symptom reduction, remission, or response rates, indicating they were equally effective in this limited sample.
Psychoactives
June 23, 2025
Georgios Mikellides
7 citations
Ketamine and esketamine are fast-acting antidepressants for treatment-resistant depression, providing symptom relief within hours—an unprecedented speed in psychiatric care. Originally anesthetics, they work through neuroplastic effects on glutamate transmission and BDNF, offering particular value for suicidal ideation. Esketamine, the S-enantiomer, is FDA- and EMA-approved as an intranasal spray for treatment-resistant depression. This narrative review synthesizes evidence on their pharmacology, efficacy, safety, and regulatory status, bridging experimental research with clinical practice.
Front Pharmacol
September 3, 2025
Georgios Mikellides, Marios Kyriazis
3 citations
Psychedelic compounds are being revisited as facilitators of profound psychological experiences with therapeutic implications for mental health conditions, particularly treatment-resistant depression and PTSD. Psilocybin has shown significant efficacy in reducing depressive symptoms in randomized controlled trials, though one study found no significant difference between psilocybin and escitalopram on the primary outcome. MDMA-assisted therapy reduced PTSD symptoms with a large effect size in a Phase 3 trial, but the FDA declined approval in 2024 due to methodological concerns. Psychedelics promote neuroplasticity and alter brain network connectivity, enabling emotional catharsis and existential re-evaluation. MDMA-assisted therapy was found cost-effective for PTSD, with net healthcare savings of $132.9 million per 1,000 patients. The article advocates for balanced, evidence-based integration into psychiatric care, emphasizing the need for rigorous trials, therapist training, and ethical protocols.
ACS chemical neuroscience
January 21, 2026
Miguel Salfiti, Marios Kyriazis, Georgios Mikellides
2 citations
Zalsupindole, a non-hallucinogenic psychoplastogen, promotes neuritogenesis and dendritic spine growth via 5-HT2-dependent mechanisms, potentially involving the mTOR pathway. In rats, it shows rapid brain penetration, no 5-HT2B agonism, no glutamate surge, and no head-twitch response. Single doses produce rapid and durable antidepressant-like effects in forced swim test and VMAT2-deficient mouse models. Phase 1 trials (2-360 mg) show good tolerability, no psychotomimetic effects, linear absorption, and dose-dependent EEG changes indicating synaptic potentiation. This biased 5-HT2A agonist may offer a new treatment for mood disorders without hallucinogenic side effects.