Treatment-Resistant Depression: A Comprehensive Insight of Ketamine Infusion Therapy, Transcranial Magnetic Stimulation (TMS), and Psychedelic-Assisted Psychotherapy

Background: The phenomenon of treatment-resistant depression (TRD) remains a problem in the sphere of mental health treatment since the majority of patients do not experience positive effects while receiving traditional treatments. Newer therapies are ketamine infusion therapy for depression, transcranial magnetic stimulation, and psilocybin-assisted psychotherapy give new hope. Objective: To evaluate the efficacy of ketamine infusion therapy, transcranial magnetic stimulation (TMS), and psilocybin-assisted psychotherapy as new treatment strategies in patients with TRD. Ketamine, which belongs to the class of NMDA receptor antagonists, has been seen to have rapid and efficient anti-depressant effects. Study Design: Retrospective review. Settings: Islamabad, Pakistan. Duration: One year and six months from December 2022 to June 2024. Methods: This study employed a systematic review methodology, searching major medical and psychological databases (PubMed, PsycINFO, Embase, and Cochrane Library) using keywords and MeSH terms related to treatment-resistant depression, ketamine infusion therapy, TMS, and psychedelic-assisted psychotherapy. Focus was on clinical trials, meta-analyses, systematic reviews, and observational studies, while excluding animal studies, case reports, and non-peer-reviewed articles. Results: The review yielded 80 studies, comprising 55 clinical trials, 10 meta-analyses, 10 systematic reviews, and 5 observational studies. The results showed that ketamine infusion therapy, Transcranial Magnetic Stimulation (TMS), and psychedelic-assisted psychotherapy demonstrated significant improvements in clinical outcomes for treatment-resistant depression. Conclusion: The review shows that ketamine infusion therapy and psychedelic-assisted psychotherapy are promising treatments for treatment-resistant depression, providing significant clinical improvements