Transcranial Magnetic Stimulation in Major Depressive Disorder
Repetitive transcranial magnetic stimulation (rTMS) should be used in adult patients with MDD who have failed to respond to at least two adequate antidepressant medication trials, as it significantly improves response and remission rates with minimal adverse effects. 1
When to Consider TMS
Initiate rTMS after documented failure of 2 or more antidepressant trials, where each trial consisted of:
- Minimum effective (approved) dosage for at least 4 weeks 1
- Different mechanisms of action between the two failed medications 1
- Adequate documentation of adherence and lack of response 2
Do not exclude patients from TMS treatment based on:
- Multiple prior medication failures (multi-drug resistance) 1
- Failed augmentation strategies 1
- Previous failed psychotherapy 1
- Prior failed electroconvulsive therapy (ECT) 1
Evidence for Efficacy
The aggregate evidence demonstrates significant benefit with rTMS showing:
- Number needed to treat of 3.4 to 9 patients for response 1
- Number needed to treat of 5 to 7 patients for remission 1
- Real-world response rates of 40-50% and remission rates of 25-30% 3
- Effect size of 0.76 when compared to sham treatment 4
One important caveat: A 2022 veteran-specific RCT found no significant differences between rTMS and sham treatment in a population with high rates of comorbid PTSD and substance use disorder, raising questions about placebo effects related to frequent clinical visits 1. However, this single study was not sufficient to overturn the broader evidence base supporting rTMS efficacy 1.
Treatment Protocol
Standard rTMS protocol consists of:
- High-frequency (10 Hz) stimulation to the left dorsolateral prefrontal cortex 5
- 20-30 daily treatment sessions over 4-6 weeks acutely 1, 4
- Biweekly maintenance sessions for up to 12 weeks 4
Accelerated protocols deliver 15 sessions over 2 days and demonstrate:
- Response rates of 36-43% 6
- Remission rates of 29-36% 6
- Comparable efficacy to standard daily protocols with excellent safety profile 6
Combination with Antidepressants
Continue antidepressants during TMS treatment rather than discontinuing them, as:
- Active TMS combined with pre-specified antidepressants shows greater efficacy than sham TMS with antidepressants (effect size = 1.0) 7
- The combination approach is more effective from treatment initiation 7
- This strategy optimizes both short-term response and long-term maintenance 7
Theta-Burst Stimulation
There is insufficient evidence to recommend for or against theta-burst stimulation (TBS) as an alternative to standard rTMS 1. While one RCT showed TBS had statistically significant improvement over sham at 12 weeks, there were no differences at 24 weeks in remission rates, and the evidence strength was very low due to small sample size 1.
Safety Profile
rTMS demonstrates excellent safety with:
- Only minimal and manageable adverse events 1
- Rare serious adverse events (seizure risk <0.1% when protocol violations are avoided) 4
- Few and minor side effects in clinical trials 4
- Benefits clearly outweighing harms 1
Practical Considerations
The primary barrier to rTMS is accessibility, as treatment requires:
- Frequent onsite visits (daily for 4-6 weeks) 1
- Specialized equipment and trained personnel 3
- Accelerated protocols may improve access by condensing treatment timeframe 6, 3
Deep TMS (dTMS) using H-coil technology allows stimulation of deeper brain structures and shows: