A patient with bipolar treatment-resistant depression who had not responded to medication, psychotherapy, or either repetitive transcranial magnetic stimulation (rTMS) or intravenous ketamine alone achieved complete and sustained remission when rTMS and ketamine were used together. The authors discuss how the two treatments may have complementary antidepressant mechanisms and call for further research on the combination's feasibility, tolerability, and efficacy.
In a real-world comparison of two FDA-approved treatments for treatment-resistant depression, intranasal esketamine led to faster improvement than repetitive transcranial magnetic stimulation (rTMS). Over 90 days, esketamine patients responded a median of 36 days versus 49 days for rTMS, and suicidal ideation resolved more quickly (median 9 vs. 26 days). However, by about 90 days, overall response and remission rates were similar between the groups (68.8% and 45.2% for esketamine; 59.4% and 40.1% for rTMS), suggesting a difference in speed rather than ultimate effectiveness. For rTMS, slower response was predicted by comorbid anxiety and benzodiazepine use, while former tobacco use predicted faster response. No such predictors were found for esketamine.