Systematic review · 2025
Review of newer treatments for hard-to-treat depression, including ketamine and psychedelics
- Original title
- Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches.
- Authors
- Tatlı SZ, Atagün Mİ
- Journal
- Actas espanolas de psiquiatria, 2025
- Molecules
- Ketamine, Esketamine, Other
- Conditions
- Treatment-resistant depression, Bipolar depression
- Evidence grade
- Low
- Source
- Read the original paper
The question
What newer options exist for treatment-resistant depression, meaning depression that has not improved with standard antidepressants, and can treatment be better matched to the individual patient?
What they did
The authors searched two research databases, PubMed and Scopus, for studies published between 2015 and 2025. They reviewed work on add-on drug strategies, mood stabilizers, atypical antipsychotics and brain stimulation techniques. They also looked at the biology thought to underlie treatment-resistant depression and at whether some of these patients may actually sit on the bipolar spectrum.
What they found
The authors report that newer interventions, including ketamine, esketamine, psychedelics and brain stimulation methods such as repetitive transcranial magnetic stimulation and magnetic seizure therapy, show promise for treatment-resistant depression. They also suggest that biomarker-based and pharmacogenetic approaches, which use biological or genetic markers to guide drug choice, could help match patients to treatments. They note that some people labelled treatment-resistant may belong to the bipolar spectrum and might do better with mood stabilizers and antipsychotics than with standard antidepressants.
The fine print
The abstract reports no numbers at all: no count of included studies, no participant totals, no effect sizes and no measure of how consistent the findings were. Ketamine, esketamine and psychedelics are only one part of a wide-ranging review, so the conclusions about them are general rather than specific. Only two databases were searched, and the abstract does not describe how study quality was assessed. This summary is based on the abstract alone.
What it means
This review places ketamine, esketamine and psychedelics among several emerging options for depression that has not responded to usual treatments, while arguing that better patient-to-treatment matching is the bigger unmet need. It is a broad overview rather than a precise estimate of how well any single treatment works.
Evidence grade: Low. A broad systematic review that summarizes many treatment types in narrative form, without pooled numbers, effect sizes or a stated number of included studies or patients.
This summary is based on the study’s published abstract.