Major depressive disorder (MDD) remains a chronic condition for many individuals, many of whom take multiple medications. Studies have shown that despite a range of pharmacotherapies, only two-thirds of patients taking multimodal treatments —including antidepressants, electroconvulsive therapy, and psychotherapy — achieve remission, and recurrence is commonly reported in up to 50% of patients within 1 year.1 The fragile state of remission in these patients has driven the investigation of therapies that can help prevent relapse and maintain long-term mood stability.

Clinical Experience With Repetitive Transcranial Magnetic Stimulation

The maintenance effects of repetitive transcranial magnetic stimulation (rTMS), a technology designed to modulate cortical excitability, are currently being investigated. “The potential is very exciting since rTMS has the potential to translate what we are learning about the neural circuit basis of depression and other disorders into circuit-guided treatments,” reported Sarah Hollingsworth Lisanby, MD, director of the translational research division at the National Institute of Mental Health (NIMH) in Bethesda, Maryland, in an interview with Psychiatry Advisor. Prior to her 2015 appointment, Dr Lisanby founded the division of brain stimulation at Columbia University, New York, and led the division of brain stimulation and therapeutic modulation at Duke University in Durham, North Carolina. “Patients often seek TMS when other treatments have failed, so often they are chronic and treatment-resistant. TMS has shown some efficacy in patients who have failed to respond to other treatments,” she said.

A good body of evidence has demonstrated the safety and efficacy of rTMS for the treatment of acute depressive symptoms,2,3 and a 2015 meta-analysis by Berlim, et al4  also reported that low frequency rTMS was superior to sham therapy for inducing remission from depression. Repetitive TMS is a noninvasive therapy that delivers electromagnetic pulses through a coil to electrodes attached to the scalp. “It is accepted by the American Psychiatric Association and the US Food and Drug Administration [FDA] as a mainstream treatment for depression,” Dr. Lisanby explained. “The FDA label describes the approved treatment parameters. Further research is needed to inform how to personalize the treatment parameters for each patient. NIMH-sponsored studies currently underway are addressing this question by using imaging and physiology to examine how rTMS works and to inform how to select patients most likely to respond to various treatment parameters.” She added that insurance coverage sometimes represents a barrier, although this is changing.

Parameters for Maintenance Therapy

According to Dr. Lisanby, clinical experience suggests that rTMS may have a place in maintenance therapy for depression, although an evidence gap still exists regarding how to best implement therapy. “NIMH supported studies are currently examining mechanisms of action, biomarkers and best methods to select patients most likely to respond, and how best to administer the therapy,” she said.

The effects of rTMS treatment on the brain are determined by several parameters, including intensity, pulse frequency, train duration, inter-train interval, pulse per session quantity, and shape and location of the coil, and the optimal settings for maintenance of remission in depression have not been identified.3

According to a new set of recommendations compiled by a consensus panel and published in early 2018,3 treatment intensity should be decided according to the level of cortical excitability. Coil placement over the left dorsolateral prefrontal cortex (DLPFC) for administration of high-frequency stimulation (10 Hz) delivered using the Brainsway Deep TMS-H1 coil has been the standard in clinical trials.3. A 2010 study by Dr. Lisanby and colleagues used a figure 8 coil set over the right DLPFC with low-frequency pulses of 1 Hz, which also demonstrated efficacy in depression.5 Use of other frequencies, coil types, and placements is considered less safe. Optimal safety is also best maintained by the combination of short pulse periods followed by long pulse-free intervals.

Sessions usually last approximately 30 to 40 minutes with an initial course of 20 to 30 sessions over a 6-week period. Efficacy in depression may begin to manifest within 2 to 3 weeks; however, current recommendations are to continue treatment for the full 6-week course.3

A 2017 meta-analysis by Fady Rachid1 that found that patients may benefit from application of rTMS as maintenance therapy following other therapies for acute bipolar or unipolar depression once a successful rTMS course has been established. In the absence of clear parameters for rTMS maintenance therapy, Dr Rachid offered alternative recommendations of a tapered protocol in which the initial treatment begins with 4 times for the first week, tapered to 3 times for week 2 and 1 to 2 times for the next 2 weeks.1 If this shows efficacy, rTMS could be continued once every 2 to 3 weeks for months to years, she concluded.

Maintenance therapy is an important component of treatment in chronic bipolar and unipolar depression to reduce the risk for relapse or remission, and rTMS appears to have a potential role in maintenance therapy in patients who have had successful prior acute treatment with or without rTMS and in patients with treatment-resistant depression.