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

Steve Best, Dan G. Pavel, Natalie Haustrup

CNS Spectrums April 1, 2021 DOI: 10.1017/s1092852920002783 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Retrospective review Randomized Peer reviewed
Sample size 28
Population Adult patients with unipolar or bipolar depression who had treatment-resistant depression
Interventions Repetitive transcranial magnetic stimulation (rTMS) Ketamine
Dose Ketamine 0.2–4.7 mg/kg IV; rTMS at 1Hz, 130% motor threshold for 40 minutes
Duration 10–30 sessions (three per week) with two-year follow-up
Measures Clinical Global Impression (CGI) scale
Topics Depression Esketamine Ketamine
Citations 1
Key findings CTK therapy produced a significant and sustained reduction in depressive symptoms, with the improvement lasting at least two years after treatment.

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.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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