Ketamine, first made in 1962, has become important for its fast-acting and lasting antidepressant effects in people with treatment-resistant depression. Unlike older antidepressants, it works through multiple brain chemical systems, including blocking NMDA receptors and boosting AMPA receptors. It also remains a useful anesthetic and painkiller for acute and chronic pain, and shows anti-inflammatory, neuroprotective, and possible antitumor properties. However, its dissociative and hallucinogenic effects lead to recreational misuse, which can cause bladder and liver problems. Its rediscovery as an antidepressant in the early 2000s transformed psychiatric care, and research now explores its use in bipolar depression, PTSD, OCD, and substance use disorders. The review covers ketamine's many uses and the need to balance benefits with risks.
Psilocybin, a psychedelic drug, is being studied for medicinal use, particularly in adult psychiatry and palliative care. Clinical trials show it may benefit patients with treatment-resistant depression and those in palliative care, often in specialist centers. It acts rapidly by targeting the 5HT2A receptor. Its psychoactive effects are well documented, but their clinical importance is debated. Many questions remain about its efficacy for other conditions and its role in psychotherapy.
A review of the neurobiology of major depressive disorder and the pharmacology, efficacy, safety, and tolerability of dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) for adults. The combination is an approved alternative for MDD, usable as a first-line therapy, as a second option after failed remission with a serotonin-targeting agent, and for treatment-resistant depression. Clinicians' familiarity with both drugs may increase acceptability, and further research into other indications, including addiction disorders, may yield additional benefits. The review is based on observational studies, clinical trials, and other secondary studies from systematic literature searches.