Background

The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) in treatment resistant patients (at least 4 medication trials) appears to be well accepted and forms the coverage policies and rTMS's use in many of the largest US payers. However, less is known about rTMS's use in patients who have undergone ≤1 failed medication trial. The purpose of this analysis was to determine the clinical efficacy of rTMS in patients after ≤1 medication trials.

Methods

A systematic review of the literature was undertaken to identify all articles which addressed the use of rTMS in ≤1 medication trial. All types of study designs were included and assessed for quality and strength of evidence using: GRADE and CEBM. Searches of peer reviewed articles were undertaken for the year 2000 to the present. All languages were considered. Electronic databases were searched and included: PubMed and EBSCO. Evidence assessment websites were also searched and included: Cochrane, NICE, AHRQ, and ICER. Additionally, the clinical guidelines for specialty societies which use rTMS was searched. Hand searches of the reference sections of identified articles was also undertaken.

Results

Electronic and other sources identified 165 after duplicates were removed. Twenty two articles were assessed for eligibility and ultimately 10 articles were included in the systematic review and graded. Six articles were graded high quality (CEBM/GRADE: 1c/B) demonstrating that the use of rTMS was clinically efficacious in patients after ≤1 medication trial. Four additional trials demonstrated a positive effect of rTMS in patients after ≤1 medication trial but were of a lower quality.

Conclusion

The use of rTMS in patients after ≤1 medication trial should be considered. US payers should consider revising their coverage policies to include the use of rTMS in these patients.

Objective

Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients' lifetime.

Methods

We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20-59) who had failed to benefit from one pharmacotherapy trial. Patients' life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%.

Results

Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year.

Conclusion

rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD.

Patients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I² = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I² = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.