Ketamine and esketamine, N-methyl-D-aspartate receptor antagonists, show promise for treating obsessive-compulsive disorder (OCD), eating disorders, and substance use disorders, which share features like obsessive thoughts and compulsive behaviors. A review of literature up to April 2021, following PRISMA guidelines, found that while small studies indicate remarkable results for treatment-resistant depression, PTSD, and OCD, solid evidence for benefits in OCD spectrum and addiction is still lacking. The use is supported by glutamatergic neurotransmission dysregulation. Preliminary data are optimistic, but further studies are needed to clarify unknowns and long-term effectiveness.
Ibogaine and noribogaine, psychedelic substances from plants of the Apocynaceae family, show some efficacy in treating substance use disorders, particularly opiate detoxification. However, their use carries concerning risks of cardiotoxicity and mortality. A meta-analysis of side effects found a significant risk of developing headaches after treatment. The evidence, drawn from case reports, randomized controlled trials, open-label studies, surveys, and observational studies, remains unclear on overall efficacy and toxicity. Further research is needed to evaluate therapeutic benefits and safety.
Psychedelics and ketamine/esketamine show promise for treating depressive disorders by inducing rapid and sustained antidepressant effects. The review examines their biological mechanisms, including modulation of glutamate and serotonin systems, promotion of neuroplasticity, and changes in brain connectivity and network function. Neuroimaging studies reveal alterations in default mode network, fronto-limbic connectivity, and thalamic activity. Clinical changes are associated with these brain alterations, though the precise relationships remain under investigation. The work synthesizes current evidence on how these compounds produce observable brain changes and symptom improvement, highlighting the need for further research to clarify mechanisms and optimize therapeutic applications.
In patients with treatment-resistant depression, combining the antidepressant vortioxetine with esketamine nasal spray was as effective as the standard combination of an SSRI or SNRI with esketamine in reducing depressive symptoms over three months. The vortioxetine combination showed a larger effect in reducing emotional blunting and was linked to fewer treatment-emergent side effects, including dissociative symptoms. These findings suggest vortioxetine plus esketamine may be a valuable alternative, though larger randomized trials are needed to confirm the results.