Synergistic use of deep TMS therapy with IV ketamine infusions for major depressive disorder: a pilot study

Major Depressive Disorder (MDD) is a pervasive psychiatric condition effecting approximately 21 million adults in the U.S. (8.4%). An estimated 30-60% of patients are resistant to traditional treatment approaches (medications and talk-therapy), alluding to the need for additional options. Two promising treatment modalities include transcranial magnetic stimulation (TMS) and ketamine infusions; both have shown efficacy in standalone studies but have scarcely been investigated synergistically in the same group of participants.

In the current study, 169 participants with treatment-resistant MDD received 36 treatments of Deep TMS-only (H1 + H7 protocols), while 66 received 36 treatments of Deep TMS (H1 + H7 protocols) and 6 IV infusions of ketamine over the course of 9 weeks. Depressive symptoms were compared pre- and -post treatment in both conditions using the PHQ-9.

In both treatment groups, depressive symptoms were significantly reduced from pre-to-post and there were no significant differences in response between the TMS + ketamine condition and the TMS-only condition. The TMS + ketamine condition had an 80.30% response rate (53 out of 66) and 43.42% remission rate (28 out of 66) compared to a 76.92% response (130 out of 169) and 39.64% remission (67 out of 16) in the TMS-only condition.

These results support the notion that TMS treatments yield high response rates in treatment-resistant cases; however, in this investigation there was no added benefit for including 6 sessions of IV ketamine in conjunction with TMS. Future investigations using randomized-control designs and robust outcome measures are warranted.