Safety and Efficacy of Transcranial Magnetic Stimulation (TMS) for Treatment-Resistant Depression
Transcranial Magnetic Stimulation (TMS) is recommended for patients with treatment-resistant depression (TRD) who have shown partial or no response to at least two adequate pharmacologic treatment trials, with evidence supporting its efficacy and safety profile showing minimal and manageable adverse events. 1
Definition of Treatment-Resistant Depression
Treatment-resistant depression is defined as:
- Failure to respond to at least two adequate trials of antidepressant medications
- Adequate trials require minimal effective dosage administered for at least four weeks 2
Efficacy of TMS for Treatment-Resistant Depression
Evidence for Efficacy
- TMS has demonstrated significantly higher response and remission rates compared to sham treatment 1
- Number needed to treat: 3.4 to 9 patients for response and 5 to 7 patients for remission 1
- Response rates of 40%-60% in treatment-resistant depression 3
- FDA approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications 4
Efficacy Considerations
- One recent RCT in a veteran population found no significant differences between rTMS and sham treatment, suggesting possible placebo effects 1
- However, the aggregate literature supports that benefits of rTMS outweigh potential harms 1
- Daily left prefrontal TMS has substantial evidence of efficacy for treating the acute phase of depression in patients who are treatment resistant 4
Safety Profile of TMS
Adverse Events
- TMS is generally well tolerated with minimal side effects 5
- Most common adverse events are mild and limited to transient scalp discomfort or pain 5
- Low dropout rate for adverse events (4.5%) 5
- Most serious risk is seizure, which occurs very rarely 3
Treatment Protocol
- Standard protocol: 5 sessions per week at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks 5
- Accelerated TMS protocols (multiple sessions per day over fewer days) have also shown promising results with comparable efficacy to standard protocols 6
Theta-Burst Stimulation (TBS)
TBS is a variation of TMS that uses rapid, repetitive pulses:
- One RCT found TBS showed statistically significant improvement over sham stimulation after 12 weeks 1
- No differences at 24 weeks in remission of depressive symptoms 1
- Evidence for TBS is currently limited by small sample sizes 1
- Current guidelines do not make a recommendation for or against the use of TBS due to insufficient evidence 1
Clinical Implementation Considerations
Patient Selection
- Best candidates are patients who have failed at least two adequate antidepressant medication trials 2
- Should be considered before more invasive interventions like deep brain stimulation 2
- Can be considered for patients who have not responded to or cannot tolerate medication treatments
Practical Challenges
- Access to TMS treatment can be challenging due to requirement for frequent onsite visits 1
- Treatment requires daily sessions for 4-6 weeks (20-30 sessions total) 4
- Insurance coverage may be a consideration for some patients
Alternative Treatments for TRD
For context, other options for TRD include:
- Ketamine or esketamine (recommended in the 2022 VA/DoD guidelines) 1
- Electroconvulsive therapy (ECT) - still considered highly effective but with more cognitive side effects 7
- Deep brain stimulation (DBS) - more invasive option for severe cases 2
Summary
TMS represents an effective, non-invasive treatment option for TRD with a favorable safety profile. The evidence supports its use in patients who have failed at least two adequate antidepressant trials, with response rates of 40-60% and minimal side effects. While access and the time commitment required for treatment may present challenges, TMS offers a valuable alternative to more invasive procedures or continued medication trials with diminishing returns.