Combination therapy with transcranial magnetic stimulation and ketamine for treatment-resistant depression: A long-term retrospective review of clinical use

Abstract

Background Both transcranial magnetic stimulation (TMS) and infused ketamine are recognized treatments for patients suffering from major depressive disorder (MDD). A novel therapy named combination TMS with ketamine (CTK) is introduced. This retrospective review examined the safety and clinical benefits of CTK in patients suffering from treatment-resistant depression (TRD) during the routine practice of psychiatry in a private clinic. Methods TRD patients (N = 28) received a coincident application of high-output TMS (30 minutes) with biomarker-determined ketamine infusions (20 minutes). Frequency of treatment was dependent on patient responsiveness (10–30 sessions). Clinical global impression (CGI) data was collected pre- and post-treatment and then two years later. Results The 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 (α = 0.01, t = 22.81 p < 0.0001). This reduction was sustained for two years following treatment completion and this remission was deemed statistically significant by a second paired t-test (α = 0.01, t = 27.36, p < 0.0001). Limitations Retrospective review of a limited number of patients undergoing CTK in a clinical practice. Conclusions This clinical review indicated that CTK is an effective, long-term therapy (after two years) and can be used for TRD patients. The coincident administration of ketamine allowed for higher TMS intensities than otherwise would be tolerated by patients. Further studies for optimization of CTK are warranted.

Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression

“…Retrospective studies including one chart review (28 cases) [ 2 ] and three case reports (with 1–3 cases per article) [ 38 – 40 ] were identified. A total of four patients received psychopharmacological and psychological therapies, and 28 patients received transcranial magnetic stimulation (TMS), to prolong the antidepressant effects of IV ketamine (Table 2 ).…”

“…A total of four patients received psychopharmacological and psychological therapies, and 28 patients received transcranial magnetic stimulation (TMS), to prolong the antidepressant effects of IV ketamine (Table 2 ). All patients enrolled in the retrospective studies were diagnosed with TRD and reported suicidal ideation [ 2 , 38 – 40 ]. Best et al [ 2 ] reported ( n = 28) on the efficacy of combination TMS with ketamine (CTK).…”

“…All patients enrolled in the retrospective studies were diagnosed with TRD and reported suicidal ideation [ 2 , 38 – 40 ]. Best et al [ 2 ] reported ( n = 28) on the efficacy of combination TMS with ketamine (CTK). The course of treatment involved 10–30 sessions of coincident treatment of 0.4–2.3 mg/kg IV ketamine (20 min) and high-output TMS (30 min).…”

“…Major depressive disorder (MDD) is a common mental disorder that causes severe functional impairment affecting approximately 10–20% of individuals at some time in their life [ 1 ]. Notwithstanding the availability of disparate psychopharmacological and psychological therapies for treating MDD, up to 40% of patients fail to achieve syndromal and functional recovery [ 2 , 3 ]. For example, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study reported that approximately half of patients with MDD failed to achieve remission of depressive symptoms following two sequential courses of conventional treatment [ 4 ].…”

Repetitive Transcranial Magnetic Stimulation for Adolescent Major Depressive Disorder: A Focus on Neurodevelopment

“…While this would not eliminate variability across participants, it reduces the effects of neurochemical brain state on the primary outcome measure. Combining rTMS and pharmacological treatment is another novel multimodal intervention being developed in adults that could be extended to adolescents ( 219 ). Notably, recent data suggest that combining antidepressant medication with a course of rTMS may in fact have a greater benefit in adolescents than in adults ( 150 ).…”