What is the effectiveness of Transcranial Magnetic Stimulation (TMS) for treatment-resistant depression?

Transcranial Magnetic Stimulation for Depression: Effectiveness and Clinical Considerations

TMS is an effective treatment for treatment-resistant depression with response rates of 29-48% and remission rates requiring treatment of 5-7 patients to achieve one remission, though its benefits appear modest and access remains challenging due to the requirement for frequent onsite visits. 1, 2

Evidence for Effectiveness

Response and Remission Rates

• The aggregate literature demonstrates that rTMS benefits outweigh harms for treatment-resistant depression, with the American College of Physicians recommending it for patients who have failed two or more adequate pharmacologic trials 1, 2
• Response rates range from 29-48% depending on the study, with a number needed to treat of 3.4 to 9 patients for response 1, 2
• Remission rates require treating 5 to 7 patients to achieve one remission 1
• In a large multisite RCT of 301 medication-free patients, active TMS was significantly superior to sham on depression rating scales at weeks 4 and 6, with remission rates approximately twofold higher with active treatment 3

Important Contradictory Evidence

• A recent RCT specifically in veterans with treatment-resistant depression found NO significant differences between rTMS and sham treatment, despite both groups showing 39% overall remission rates 1
• This veteran study included 164 patients with high rates of comorbid PTSD and substance use disorders, raising concerns that placebo effects from frequent clinical visits and patient expectancy may play a substantial role in rTMS outcomes 1
• The VA/DoD guideline work group did not modify their recommendation based on this single negative study, but it represents an important caveat 1

Treatment Parameters and Protocols

Standard rTMS Protocol

• Treatment consists of 10 Hz stimulation to the left dorsolateral prefrontal cortex at 120% motor threshold 3
• Sessions deliver 3,000 pulses per session, conducted 5 times per week for 4-6 weeks 3
• The treatment is well-tolerated with only 4.5% dropout rate for adverse events, which are typically mild and limited to transient scalp discomfort 3

Theta-Burst Stimulation (TBS)

• There is insufficient evidence to recommend for or against theta-burst stimulation, a rapid variation of TMS 1, 2
• One RCT showed TBS was statistically superior to sham at 12 weeks but not at 24 weeks for remission 1
• A study comparing intermittent TBS to standard 10 Hz rTMS found no difference in benefit, but sample sizes were too limited for definitive conclusions 1

Accelerated Protocols

• Accelerated TMS (15 sessions over 2 days) showed response rates of 43% immediately post-treatment and 36% at 3 and 6 weeks in an open-label study 4
• Remission rates were 29-36% across timepoints, comparable to daily rTMS protocols 4
• However, 36% of patients failed to complete all study visits, indicating potential tolerability concerns with intensive protocols 4

Practical Access Barriers

Treatment Burden

• The primary challenge for rTMS is access, as it requires frequent onsite visits (typically 5 sessions per week for 4-6 weeks) 1, 2
• This represents 20-30 total visits, creating significant logistical and time burden for patients 1

Mechanism and Durability Considerations

Structural Brain Changes

• ECT produces greater volumetric brain changes than rTMS in regions including the striatum, pallidum, medial temporal lobe, and subgenual anterior cingulate cortex, despite comparable clinical outcomes 5
• This suggests rTMS may work through neurophysiological plasticity rather than structural neuroplasticity or neuroinflammation 5
• The lack of structural changes with rTMS may explain why it produces more durable therapeutic benefits compared to ECT, as it avoids potential inflammatory processes 5

Clinical Recommendations

Patient Selection

• Reserve TMS for patients with major depressive disorder who have shown partial or no response to at least two adequate pharmacologic treatment trials 1, 2
• Consider that patients with high comorbidity burden (particularly PTSD and substance use disorders) may have less robust responses based on the veteran population study 1
• Patients must be able to commit to 4-6 weeks of daily weekday visits 1

Setting Expectations

• Inform patients that approximately 1 in 3 to 1 in 2 will experience meaningful response 1, 2
• Emphasize that remission is less common, occurring in roughly 1 in 5 to 1 in 7 patients 1
• Discuss that placebo effects may contribute substantially to outcomes, particularly given the intensive clinical contact 1

Comparison to Other Treatments

• While ECT remains more effective overall, rTMS is less invasive, better tolerated, and may produce more durable benefits 5
• For patients who have failed multiple medication trials but are not candidates for or refuse ECT, TMS represents a reasonable intermediate option 1, 2