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

Combining repetitive transcranial magnetic stimulation (rTMS) with intravenous ketamine infusions—called combination TMS with ketamine (CTK)—produced substantial and lasting reductions in depressive symptoms for 28 adults with treatment-resistant depression. Patients received three CTK sessions per week, with rTMS applied to the mid-prefrontal area and ketamine doses adjusted by biomarker levels. Symptom severity, measured by the Clinical Global Impression scale, dropped significantly after treatment, and the improvement persisted for at least two years. The findings suggest CTK may help patients who have not responded to other treatments, but randomized controlled trials are needed to confirm the results.

Study at a glance

Abstract

AbstractBackgroundRepetitive 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).MethodsA 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.ResultsMean 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.ConclusionsDespite 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.