TMS for Persistent Depressive Disorder
Transcranial magnetic stimulation (TMS) should be offered to patients with persistent depressive disorder who have failed to respond to at least two adequate antidepressant trials (minimum effective dose for ≥4 weeks each), with expected response rates of 41-51% and remission rates of 24-35%. 1, 2, 3, 4
Evidence-Based Recommendation
The 2022 VA/DoD guidelines explicitly recommend rTMS for patients with major depressive disorder—which encompasses persistent depressive disorder—who have shown partial or no response to two or more adequate pharmacologic treatment trials. 1, 3 This recommendation is supported by aggregate literature showing number needed to treat of 3.4 to 9 patients for response and 5 to 7 patients for remission. 1, 3
Treatment Protocol
Standard acute treatment course:
- Daily sessions (5 days per week) for 4-6 weeks, targeting the left dorsolateral prefrontal cortex 1, 3, 5
- Total of 20-30 treatment sessions in the acute phase 4, 5
- Can be administered adjunctively with ongoing antidepressant medications 4
For acute non-responders:
- Continue with twice-weekly maintenance TMS for an additional 4-12 weeks, as 61% of initial non-responders achieved response with continued treatment 6
- Among those entering 6-month maintenance treatment, 62% maintained responder status 4
Expected Outcomes in Treatment-Resistant Populations
Real-world effectiveness data from 100 consecutive patients at an academic medical center (mean 3.4 failed adequate trials, 60% with prior psychiatric hospitalization) demonstrated:
- CGI-I response rate: 50.6% 4
- CGI-I remission rate: 24.7% 4
- HDRS response rate: 41.2% 4
- HDRS remission rate: 35.3% 4
- Mean HDRS reduction: -7.8 points 4
Critical Caveats
Conflicting evidence in specific populations: One 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 may play an important role in outcomes. 1, 3 However, this single study was insufficient to modify the overall recommendation given the aggregate positive literature. 1, 3
Access barriers: TMS requires frequent onsite visits (typically daily for 4-6 weeks), which represents a significant practical limitation. 1, 3
Insufficient evidence for theta-burst stimulation: Despite TBS offering shorter treatment sessions, current guidelines state there is insufficient evidence to recommend for or against its use. 1, 3
Safety Profile
TMS demonstrates excellent tolerability with only 3% discontinuation rate in acute treatment and no serious adverse events related to TMS in both acute and maintenance phases. 4 The primary side effect is transient scalp discomfort at the stimulation site. 4
When to Consider TMS
Verify TRD diagnosis first:
- Document at least 2 failed antidepressant trials with different mechanisms 2
- Each trial must be at minimum effective dosage for ≥4 weeks 2
- Discontinuation due to side effects before 4 weeks should not count as treatment failure 2
TMS fits in the treatment algorithm after: