This systematic review examines how psychedelic-assisted therapies like ketamine and psilocybin help people with severe, treatment-resistant depression that doesn’t respond to standard antidepressants. The analysis of 10 recent clinical trials shows these therapies work quickly, often providing symptom relief within days rather than weeks, and importantly, they also help people return to work and daily functioning. These treatments are generally well-tolerated with minimal cognitive side effects, suggesting they could become important new options for patients who haven’t benefited from conventional depression treatments.