In a real-world clinical setting, 45 patients with treatment-resistant bipolar depression received intravenous ketamine or intranasal esketamine. Among 38 who completed an acute series (twice-weekly treatments for up to four weeks), 39% achieved a clinical response (at least 50% improvement on the Montgomery-Asberg Depression Rating Scale) and 13.2% achieved remission (score of 10 or lower). Mean depression scores dropped from 31.1 to 19.2, a 38.3% improvement. No manic or hypomanic episodes occurred during the acute phase. However, during maintenance treatment, 28.9% of patients experienced hypomanic or manic symptoms, with one severe event requiring hospitalization.
Both repetitive transcranial magnetic stimulation (rTMS) and intranasal esketamine are more effective than starting a new antidepressant medication for treatment-resistant depression. In a secondary analysis of individual patient data from two clinical trials involving 282 matched participants, rTMS reduced depression severity scores by 5.35 points and esketamine by 2.89 points more than medication alone. The difference between rTMS and esketamine was not statistically significant, but the results suggest rTMS may be at least as effective as esketamine. The analysis highlights the need for direct head-to-head trials comparing these two interventions.