What is the role of Transcranial Magnetic Stimulation (TMS) in treating major depressive disorder?

Role of Transcranial Magnetic Stimulation in Major Depressive Disorder

Transcranial Magnetic Stimulation (TMS) is recommended for patients with major depressive disorder (MDD) who have shown partial or no response to two or more adequate pharmacologic treatment trials. 1

Definition of Treatment-Resistant Depression (TRD)

Treatment-resistant depression is commonly defined as:

• Depression that fails to respond (decrease in severity by at least 50%) or achieve remission following two or more treatment attempts of adequate dose and duration 1
• Adequate treatment typically requires:
  • Minimum effective dosage (minimal approved dosage)
  • Duration of at least 4 weeks 1

TMS Treatment Protocol and Efficacy

Standard Protocol

• Location: Left dorsolateral prefrontal cortex (DLPFC)
• Frequency: 5 sessions per week
• Parameters: 10 pulses/second, 120% of motor threshold, 3000 pulses/session
• Duration: 4-6 weeks (20-30 sessions) 2, 3

Efficacy Evidence

• TMS shows significantly superior outcomes compared to sham treatment:
  • Higher response rates on depression rating scales at weeks 4 and 6
  • Approximately twofold higher remission rates at week 6 2
• Number needed to treat: 3.4 to 9 patients for response and 5 to 7 patients for remission 1

Patient Selection Algorithm

1. Confirm diagnosis of MDD using standard clinical evaluation or structured clinical assessment 1

2. Verify treatment resistance:

   • Document failure of at least 2 adequate antidepressant trials
   • Each trial should be at minimum effective dose for at least 4 weeks 1

3. Consider TMS when:

   • Patient has shown partial or no response to adequate pharmacologic trials
   • Patient is intolerant to medication side effects 3

4. No exclusion based on prior treatment failures:

   • Prior failed psychotherapy is not an exclusion criterion
   • Prior failed non-invasive brain stimulation (like ECT) is not an exclusion 1
   • Patients with multiple medication failures should not be excluded 1

5. Exclusion criteria:

   • Patients with bipolar depression (not MDD) 1
   • Patients who have failed deep brain stimulation (DBS) or vagus nerve stimulation (VNS) 1

Safety Profile

TMS demonstrates an excellent safety profile:

• Low discontinuation rate (4.5%) due to adverse events 4
• Most common adverse events are mild to moderate:
  • Transient headaches
  • Scalp discomfort 4
• No significant impact on:
  • Auditory threshold
  • Cognitive function 4
• No reported seizures in large clinical trials 4

Clinical Considerations and Pitfalls

Access Challenges

• One primary challenge is access to TMS treatment due to requirement for frequent onsite visits 1

Placebo Effect Considerations

• Some studies suggest placebo effects may play a role in TMS outcomes
• A veteran population study showed high remission rates (39%) but no significant differences between active and sham TMS 1
• However, aggregate literature supports TMS efficacy over placebo 1

Theta-Burst Stimulation (TBS)

• TBS is a variation of TMS using rapid, repetitive pulses
• Current evidence is insufficient to recommend for or against TBS
• Limited studies show TBS may have statistically significant improvement over sham at 12 weeks but not at 24 weeks 1

Mechanism of Action

TMS produces multiple physiological changes that may contribute to its antidepressant effects:

• Neurochemical changes at stimulation site
• Correction of functional connectivity abnormalities that are characteristic of MDD
• Distant neurotransmitter effects 5

Comparison with Other Treatment Options

For treatment-resistant depression, clinicians should consider:

1. TMS: For patients who failed 2+ medication trials
2. Ketamine/Esketamine: Also suggested for patients who have not responded to several adequate pharmacologic trials 1
3. Bright Light Therapy: Recommended for mild to moderate MDD, regardless of seasonal pattern 1

TMS offers a well-tolerated, non-invasive alternative that can be safely administered in outpatient settings for patients with treatment-resistant depression 4.