Combination of Transcranial Magnetic Stimulation and Ketamine in Treatment-Resistant Depression: A Systematic Review

Treatment-resistant depression (TRD) is a significant challenge in psychiatric practice, affecting a substantial proportion of patients with major depressive disorder (MDD). Traditional treatment modalities often fall short, necessitating the exploration of alternative therapies. This literature review examines the combined use of Transcranial Magnetic Stimulation (TMS) and ketamine in treating TRD. The objective of this study is to evaluate the efficacy, safety, and potential synergies of combining TMS and ketamine in the treatment of TRD. A comprehensive literature search was conducted using PubMed and Google Scholar databases from 2014 to 2024. The search terms included combinations of "Transcranial Magnetic Stimulation," "Ketamine," "Depression," "Major Depressive Disorder," "Treatment-Resistant Depression," and "Combination." After screening for relevance and applying inclusion and exclusion criteria, six studies were selected for review, including three case reports, a retrospective study, a pilot study, and a review study. The selected studies demonstrated that the combination of TMS and ketamine resulted in substantial and sustained improvement in depressive symptoms for patients with TRD. Case reports and retrospective studies highlighted significant reductions in depression severity and improvements in psychosocial functioning. The combination therapy showed a higher efficacy compared to monotherapies of either TMS or ketamine alone. Notably, adverse effects were generally mild and transient, with no severe adverse events reported in most studies. In conclusion, the combination of TMS and ketamine presents a promising treatment modality for patients with TRD, offering significant improvements in depressive symptoms and better outcomes compared to traditional monotherapies. However, the heterogeneity in study designs and small sample sizes underline the need for larger, randomized controlled trials to establish standardized protocols and further validate these findings.