What is the reasoning behind a Transcranial Magnetic Stimulation (TMS) dip in patients undergoing TMS treatment for depression?

Understanding the TMS Dip Phenomenon

What is the TMS Dip?

The "TMS dip" refers to a temporary worsening of depressive symptoms that can occur during the initial 1-2 weeks of repetitive transcranial magnetic stimulation (rTMS) treatment, before therapeutic benefits emerge. This phenomenon is clinically important because it requires at least 4-6 weeks of daily rTMS over the left dorsolateral prefrontal cortex (DLPFC) to induce significant clinical improvement compared to sham stimulation 1.

Neurobiological Mechanisms Behind the Dip

Initial Cortical Disruption Phase

• The magnetic pulses initially disrupt existing neural patterns before establishing new, healthier connectivity. During online rTMS, stimulation at specific frequencies (particularly 5 Hz) can temporarily disrupt reaction time and cognitive processing 2.
• The brain undergoes neural entrainment and synaptic plasticity changes that take time to consolidate into therapeutic effects 3.
• Electric field modeling reveals that TMS induces diffuse current flow representing a large area of potentially stimulated cortex, which requires time for reorganization 2.

Insufficient Treatment Duration Effect

• Studies performing rTMS for only 3 weeks found no difference between active and sham treatment, demonstrating that the therapeutic window has not yet been reached during the early "dip" phase 1.
• The number of treatment sessions is critical—protocols with 8-14 sessions or more show better sustained outcomes, but early sessions may not yet demonstrate benefit 1.

Clinical Timeline and Expectations

Week 1-2: The Dip Period

• Patients may experience transient worsening of depressive symptoms 4, 5.
• This occurs as the brain adjusts to daily electromagnetic stimulation targeting cortical neurons 2.
• Anxiety symptoms may also temporarily increase during this adjustment phase 4.

Week 3-4: Emergence of Benefits

• Response rates begin to manifest as neural plasticity consolidates 1, 6.
• Standard protocols show response rates of 29-48% by treatment completion 7, 1.

Week 4-6: Full Therapeutic Effect

• Remission rates require treatment of 5-7 patients (number needed to treat) by this timepoint 1.
• Effects can be maintained for 3-6 months following a standard acute treatment course 1.

Critical Clinical Implications

Patient Counseling is Essential

• Warn patients explicitly about the potential for initial symptom worsening to prevent premature discontinuation. In one accelerated TMS study, 36% of patients failed to complete all study visits, partly due to unexpected early effects 4.
• Set realistic expectations that meaningful improvement requires commitment to the full 4-6 week course 1.

Monitoring During the Dip

• Increased vigilance for suicidal ideation is warranted during weeks 1-2, as one study reported increased suicidal ideation as a serious adverse event during this period 4.
• Ensure concurrent mood stabilizer treatment remains optimized, as this supports safety during the adjustment phase 8.

When to Persist vs. Discontinue

• Continue treatment through the dip unless there are safety concerns (seizure risk, severe suicidal ideation, or intolerable side effects). The dip is a neurobiological adjustment period, not treatment failure 4, 5.
• Only highly motivated patients should be recruited for intensive protocols given the daily treatment burden and initial symptom fluctuation 1.

Factors That May Influence Dip Severity

Stimulation Parameters

• Frequency matters: 10 Hz pulses are most commonly used (49% of studies), while 5 Hz specifically disrupts cognitive processing during the adjustment phase 2.
• Intensity of 120% motor threshold with 3,000 pulses per session represents standard dosing that balances efficacy with tolerability 8.

Patient-Specific Variables

• Older age may be associated with more pronounced initial effects due to age-related cortical inhibition limiting plasticity 9.
• Concurrent medications influence the trajectory: lamotrigine is associated with lower depression scores throughout treatment, while lithium may be associated with higher scores 8.

Practical Management Algorithm

1. Pre-treatment phase: Counsel patients about the 1-2 week dip phenomenon and obtain commitment to 4-6 weeks of daily sessions 1, 4.

2. Weeks 1-2 (Dip period): Increase monitoring frequency, assess for suicidal ideation at each visit, and reinforce that temporary worsening is expected 4.

3. Week 3: Re-evaluate symptoms; if no improvement yet, continue treatment as therapeutic effects typically emerge by week 4 1, 6.

4. Weeks 4-6: Assess response (≥50% symptom reduction) and remission (near-complete resolution); consider maintenance protocols if response achieved 1, 8.

5. Post-acute phase: Plan maintenance treatment (twice weekly for 3 months) to extend response duration from 3-6 months 1.