What is the typical treatment protocol and need for long-term maintenance sessions for Transcranial Magnetic Stimulation (TMS) therapy in an adult patient with treatment-resistant depression?

Transcranial Magnetic Stimulation (TMS) for Depression: Treatment Protocol and Maintenance

How TMS Works

TMS delivers magnetic pulses to the brain cortex that generate electrical currents strong enough to modulate neural activity but not intense enough to provoke seizures, producing therapeutic effects through changes in neuroplasticity. 1

• The magnetic fields stimulate targeted brain regions, typically the left dorsolateral prefrontal cortex (DLPFC), to normalize activity patterns disrupted in depression 1
• The exact mechanisms remain incompletely understood but involve modulation of glutamatergic receptors, NMDA and AMPA receptor signaling, and potentially BDNF expression 2
• Effects are thought to occur through long-term potentiation (LTP) and long-term depression (LTD)-like plasticity mechanisms 2

Standard Acute Treatment Protocol

The typical acute treatment course requires 20-30 daily sessions over 4-6 weeks, with high-frequency stimulation (10 Hz) applied to the left DLPFC at 100-120% of resting motor threshold. 2, 3

• At least 4-6 weeks of daily rTMS is required to induce significant clinical improvement compared to sham stimulation 2, 3
• Studies using only 3 weeks of treatment showed no difference between active and sham rTMS, indicating insufficient duration 2, 3
• Standard protocols deliver approximately 1800 pulses per daily session 2
• Treatment requires frequent onsite visits (typically 5 sessions per week), which poses a significant access challenge 2, 3

Treatment Efficacy

The American College of Physicians recommends TMS for patients with major depressive disorder who have shown partial or no response to two or more adequate pharmacologic treatment trials, with response rates of 29-48% and remission rates requiring treatment of 5-7 patients for one remission. 3

• Response rates in real-world clinical settings range from 36-46%, with remission rates of 12-42% depending on measurement tools used 4, 5
• The aggregate literature suggests benefits of rTMS for treatment-resistant depression outweigh harms, with only minimal and manageable adverse events 2
• One critical caveat: A recent RCT in veterans with high rates of comorbid PTSD and substance use disorder found no significant differences between rTMS and sham treatment, suggesting placebo effects from frequent clinical visits may play an important role 2, 3

Duration of Response and Need for Maintenance

Response can be maintained for 3-6 months following a standard acute treatment course, but the majority of studies (71%) lack follow-up data beyond the day of intervention. 3

Evidence for Response Duration:

• Reduced symptoms persisted for up to 6 months in some addiction-related applications following 13 sessions 2, 3
• Enhanced abstinence rates lasted up to 3 months following just 4 sessions of theta burst stimulation in smokers 2, 3
• Only 2 studies included one-year follow-up, 6 studies had six-month follow-up, and 4 studies had three-month follow-up 3

Maintenance Treatment Strategies:

Some protocols incorporate maintenance interventions of twice-weekly sessions for 3 months following the acute treatment phase to extend response duration. 2, 3

• In alcohol dependency, twice-daily sessions with 20-minute intervals led to positive effects lasting up to 6 months 2, 3
• Weekly applications over 5 weeks showed sustained effects in some addiction studies 2
• The optimal maintenance schedule remains unclear due to heterogeneity in protocols across studies 3

Important Clinical Caveats

Only highly motivated patients should be selected for TMS given the daily treatment burden and high visit frequency requirements. 2, 3

• Drop-out rates in clinical settings are relatively low (12.5%) when patients are appropriately selected 5
• No serious adverse events are typically reported during treatment 6, 5
• The relatively large heterogeneity in stimulation technique, timing, repetition, and montage across studies precludes clear understanding of optimal protocols 3
• Standard 4-week protocols may not be effective in chronic, severe treatment-resistant patients with multiple failed treatments 7

Theta Burst Stimulation (TBS) Variant

There is insufficient evidence to recommend for or against theta-burst stimulation, a rapid variant of TMS that delivers treatment in shorter sessions. 2, 3, 8

• TBS showed statistically significant improvement over sham at 12 weeks but no differences at 24 weeks for remission 2
• TBS demonstrated non-inferiority to standard 10 Hz rTMS in some studies 2, 8
• The evidence remains too limited with small sample sizes to make definitive recommendations 2