Long-Term Efficacy of Combination Therapy of Transcranial Magnetic Stimulation with Ketamine for Patients with Treatment-Resistant Depression

This retrospective review (n=28) investigated the clinical benefits of combining two therapies, repetitive transcranial magnetic stimulation (rTMS) and ketamine infusion (together CTK), for patients with treatment-resistant depression (TRD). The review found that all 28 patients experienced significant and enduring (two years) decreases in their depressive moods post the CTK therapy. The review also called for further research into method optimization and randomized controlled trials.


Background: Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive treatment for many psychiatric illnesses, including treatment-resistant depression (TRD). Ketamine, an NMDA receptor antagonist, is also an effective antidepressant. This retrospective review examined the clinical benefits of combining these two established treatments for patients suffering from TRD in a novel approach coined combination TMS with ketamine (CTK).

Methods: A group of 28 adult patients with a primary diagnosis of unipolar (n=18) or bipolar (n=10) depression received three CTK treatments a week at a private neuropsychiatric practice. Patients were given a concurrent treatment of rTMS (1Hz; 40 minutes; 130% of motor threshold) with bio-marker-determined IV ketamine infusions (0.2-4.7 mg/kg; 30 minutes). The TMS coil was positioned on the mid-prefrontal area. Frequency of treatment was dependent on patient responsiveness (10-30 sessions), which was measured as symptom reduction on the Clinical Global Impression (CGI) scale. CGI data was evaluated pre-treatment, post-treatment and at two-year follow-up.

Results: Mean reduction in CGI severity for the patient group following CTK was 4.46 ± 0.54 at a 99% confidence interval and was deemed statistically significant using a paired t-test (a=0.01, t=22.81, p < 0.0001). This significant reduction in CGI severity was sustained for at least 2 years following treatment completion.

Conclusions: Despite years of unsuccessful treatments, all 28 patients in this trial obtained substantial and enduring reductions in their depressive symptoms following CTK therapy. Further research into method optimization and randomized controlled trials are warranted.”

Authors: Steven R. D. Best, Dan G. Pavel & Natalie Haustrup


This paper was originally published as Best and colleagues (2019).

Study details

Compounds studied

Topics studied
Depression Treatment-Resistant Depression

Study characteristics
Open-Label Follow-up