What is Theta Burst Stimulation (TBS) in the treatment of depression?

What is Theta Burst Stimulation?

Theta burst stimulation (TBS) is a faster, patterned form of repetitive transcranial magnetic stimulation (rTMS) that delivers magnetic pulses in specific bursts to modulate brain activity, primarily used to treat treatment-resistant depression when patients have failed at least 2 adequate antidepressant trials. 1

Technical Description

TBS is a noninvasive brain stimulation technique that uses magnetic pulses to modify neural network activity in psychiatric and neurological disorders. 2 The technique can be delivered in two main patterns:

• Intermittent TBS (iTBS): Applied to increase cortical excitability, typically targeting the left dorsolateral prefrontal cortex 3
• Continuous TBS (cTBS): Applied to inhibit cortical activity, typically targeting the right dorsolateral prefrontal cortex 3

Key Advantages Over Standard rTMS

TBS protocols deliver treatment much faster than conventional 10 Hz rTMS—a single TBS session takes approximately 3-10 minutes compared to 37.5 minutes for standard rTMS. 2 This brevity makes TBS particularly well-suited for accelerated treatment schedules where multiple sessions can be delivered per day. 2, 4

Clinical Efficacy in Depression

Despite demonstrated non-inferiority to standard rTMS, the 2022 VA/DoD guidelines state there is insufficient evidence to make a recommendation for or against theta-burst stimulation. 5, 1 This cautious stance contrasts with the FDA approval of conventional intermittent TBS for treatment-resistant depression. 2

Recent naturalistic studies show:

• Response rates of 36-47% and remission rates of 26-34% for both unilateral and bilateral TBS protocols 6
• Bilateral TBS may require fewer treatment sessions (27 vs 29 sessions) and demonstrates superior anxiolytic effects compared to unilateral approaches 6
• 69% of responders maintain improvement at 6 months without additional treatment 6

Treatment Protocols

Standard Bilateral Sequential TBS

• iTBS (600 pulses) to left DLPFC followed by cTBS (600 pulses) to right DLPFC 4, 3
• Typically delivered daily for 20-30 sessions over 4-6 weeks 6, 3
• Stimulation intensity: 80-120% of resting motor threshold 7

Accelerated Protocols

• Multiple sessions delivered per day (up to 5 sessions daily) 4
• Treatment course compressed to 5-10 days instead of 4-6 weeks 4, 7
• No significant difference in efficacy between sub-threshold (80%) and supra-threshold (120%) intensities 7

Patient Eligibility

Patients appropriate for TBS include those with treatment-resistant depression who have failed at least 2 adequate antidepressant trials (minimum 4 weeks each at therapeutic dose) within the current depressive episode. 1

Do not exclude patients based on:

• Multiple prior medication failures 1
• Previous ECT or TMS failure 1
• Comorbid personality disorders 1
• High rates of comorbid PTSD or substance use disorders 1

Critical caveat: Medication trials discontinued before 4 weeks due to side effects should not be counted as failed trials. 1, 8

Safety Profile and Cognitive Effects

High-frequency stimulation like TBS can temporarily disrupt memory precision during active treatment, with effects being temporary and limited to the treatment period. 1, 9

Specific cognitive effects include:

• TBS at 10 Hz significantly impairs performance on language, memory, motor function, and perception tasks 9
• 20 Hz stimulation disrupts attention, executive functions, memory, and perception 9
• These effects are transient and resolve after treatment completion 9

Patients should be informed about possible transient memory difficulties during active treatment. 1, 9 In one accelerated bilateral TBS study, 60% of patients could not tolerate high-intensity stimulation, though no major adverse events occurred. 4

Clinical Outcomes Compared to Standard rTMS

A large randomized controlled trial (n=300) found no significant differences in response or remission rates between accelerated bilateral TBS and standard unilateral 10 Hz rTMS, with an overall response rate of 43.7% and remission rate of 28.2%. 7 Importantly, accelerated TBS application was not associated with more rapid antidepressant effects despite the compressed treatment schedule. 7

Common Pitfalls to Avoid

• Do not assume faster treatment equals faster response: Accelerated protocols compress treatment duration but do not necessarily produce more rapid symptom improvement 7
• Do not use higher intensities expecting better outcomes: Studies show no significant efficacy difference between 80% and 120% motor threshold intensities 7
• Do not deny treatment based on prior TMS failure: Previous non-response to rTMS does not disqualify patients from TBS trials 1