Therapeutic neuromodulation takes advantage of the brain’s electrochemical makeup. This allows for treatment devices that modulate neurocircuits relevant to behaviors disrupted in disorders such as major depressive disorder (MDD) (eg, sleep quality, appetite, cognitive, and executive functions). The default mode network (comprised of structures such as the medial prefrontal cortex [MPFC], the posterior cingulate cortex, the hippocampus, and their functional connectivity) serves as a prime example of circuitry that can be targeted by this approach.1
For 80 years, electroconvulsive therapy (ECT) has been an important neuromodulation option for patients with more severe illness. Recently, additional neuromodulatory approaches have been FDA-cleared, including transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Another approach, transcranial direct current stimulation (tDCS), has been extensively studied for its potential clinical utility but is not FDA-cleared. The Table provides descriptions of these therapies.
Since being cleared by the FDA in 2008, TMS has arguably made the greatest strides in providing an alternate neuromodulation treatment option for patients with MDD, with >1,000 centers nationally and 7 TMS devices FDA-cleared for treatment of depression. In this article, we review recent developments in TMS.
An evolving therapeutic option
While primarily studied as a monotherapy for MDD, in clinical practice TMS (Box) is typically used as an adjunct to medication and psychotherapy.2,3 In this context, it has demonstrated efficacy for more difficult-to-treat mood disorders with an excellent safety and tolerability profile whether used with or without medication.4-6
To further improve the efficiency and efficacy of TMS while maintaining its safety and tolerability, researchers and clinicians have been exploring a few initiatives.
Box
Key points: Transcranial magnetic stimulation
- Transcranial magnetic stimulation (TMS) utilizes intense, localized magnetic fields to alter activity in neural circuits implicated in the pathophysiology of depression
- Randomized, sham-controlled acute trials have demonstrated the efficacy of TMS for treatment-resistant depression
- Clinical availability of TMS has grown steadily over the past 10 years as >1,000 centers have been opened and additional devices have been FDA-cleared
- TMS has the potential to avoid safety and tolerability concerns associated with antidepressant pharmacotherapy (eg, weight gain, sexual dysfunction) and electroconvulsive therapy (eg, cognitive deficits)
- Greater sophistication in the choice of stimulation parameters, as well as other ongoing efforts to optimize the benefits of TMS, are yielding better clinical outcomes
Altered treatment parameters
One initiative is assessing the feasibility of altering various treatment parameters, such as the total number of treatment sessions (30 to 60 sessions); the frequency of sessions (eg, more than once daily); the total number of magnetic pulses per session (eg, >3,000); the stimulation coil localization (eg, left vs right dorsal lateral prefrontal cortex [DLPFC]; MPFC; and various methods to determine optimal coil placement (eg, EEG F3 coordinate or MRI-guided neuro-navigational methods). Such refinements offer the potential for enhanced efficacy, shorter treatment sessions, and/or improved tolerability. For example, lower frequency right DLPFC stimulations (eg, 1 Hz) can decrease the risk of seizures and improve overall tolerability. While this has not been studied as extensively as higher frequency left DLPFC stimulations (eg, 5 to 20 Hz), existing evidence supports similar efficacy between these 2 approaches.7
Theta burst stimulation. Some TMS devices can be adapted to deliver theta burst stimulation (TBS). This produces trains of triple, 50 Hz, pulsed bursts (usually with 200 ms inter-burst intervals occurring at a rate of 5 Hz; at 80% MT) to model naturally occurring theta rhythms. These bursts can be administered in stimulation protocols using intermittent TBS (iTBS) (eg, 10 bursts of triplets over 2 seconds every 10 seconds; 30 pulses per burst; for approximately 3 minutes; totaling 600 pulses) or continuous TBS (cTBS) bursts given in an uninterrupted train (eg, 40 seconds, 600 pulses). Evidence indicates these protocols facilitate long-term potentiation (ie, iTBS) and long-term depression (ie, cTBS), which in turn can modulate synaptic plasticity.
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