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Phase II Trial: Combined TMS and Ketamine Doubles Remission in Treatment-Resistant Cases

A Phase II trial reported 78% remission at four weeks for combined TMS and intravenous ketamine compared with 45% for TMS alone and 39% for ketamine alone.

Research Studies August 30, 2025 · Biological Psychiatry ↗

A Phase II trial conducted at three academic medical centers reported that combining transcranial magnetic stimulation with intravenous ketamine produced a 78% remission rate at four weeks in patients with treatment-resistant depression — substantially higher than the 45% and 39% remission rates for either treatment alone in the same trial.

The 156-patient trial randomized participants to one of three arms: standard 10Hz TMS for six weeks, six ketamine infusions over three weeks, or both treatments delivered concurrently. Adverse events were additive but not synergistic; dissociative symptoms during ketamine infusions resolved within hours and did not interfere with subsequent TMS sessions.

The mechanistic rationale is that ketamine produces rapid synaptic plasticity that may amplify the network-level effects of TMS. The authors caution that the combined protocol is logistically demanding, requires monitored anesthesia care for the ketamine arm, and has not yet been studied for durability beyond eight weeks.

A confirmatory Phase III trial is in planning. Insurance coverage for combined regimens does not currently exist outside of academic medical centers.

Source

Reporting based on coverage from Biological Psychiatry. This article is editorial summary intended for general information; it is not medical advice.

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