Theta-burst stimulation for depression

Optimization of Prefrontal Theta-Burst Stimulation to Treat Depression: A Bench to First-in-Human Study

This trial tests two timing schedules of intermittent theta-burst stimulation (a quick form of TMS) to see which better improves brain plasticity and reduces depressive symptoms in adults 18–50 with major depressive disorder.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: Centre for Addiction and Mental Health (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07033780 on ClinicalTrials.gov

What this trial studies

Researchers will compare compressed iTBS (iTBS-c), the commonly used schedule, with spaced iTBS (iTBS-s) in adults aged 18–50 with major depressive disorder. Participants who meet inclusion criteria will receive one of the iTBS protocols delivered to the dorsolateral prefrontal cortex, with neurophysiological and clinical measures collected before and after treatment. Outcomes will include markers of cortical plasticity (LTP-like responses in motor and prefrontal regions) and changes in depression severity using standardized scales. The aim is to identify which timing protocol produces larger and more durable neuroplastic and clinical effects.

Who should consider this trial

Good fit: Adults 18–50 years old with a current major depressive episode (HRSD-17 > 7), able to provide informed consent, right-handed or ambidextrous, and stable on any antidepressant for at least four weeks are ideal candidates.

Not a fit: People outside the 18–50 age range or with other major psychiatric or neurologic diagnoses associated with prefrontal dysfunction, or with unstable medications, are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the preferred timing protocol could provide faster or more durable symptom improvement by enhancing brain plasticity with a brief treatment time.

How similar studies have performed: Prior animal and human work indicates iTBS can induce sustained cortical plasticity and achieve clinical effects similar to conventional rTMS, but comparisons of different spacing schedules remain limited.

Eligibility criteria

Inclusion Criteria:

* Aged 18-50 years old;
* Must meet criteria for a current Major Depressive Episode (MDE) as ascertained using the Structured Clinical Interview for DSM 5 (SCID-5);
* Hamilton Rating Scale for Depression (HRSD-17) score \> 7;
* Must be on a stable antidepressant regimen for a minimum of 4 weeks prior to enrollment, if currently taking antidepressants;
* Right handed or ambidextrous, assessed using the Edinburgh Handedness Inventory (EHI);
* Sufficiently proficient in English to complete the required study assessments, as per investigator judgement;
* Willingness and capacity to provide informed consent;
* Willingness to comply with all study procedures.

Exclusion Criteria:

* Age 17 years or less, or greater than 51 years old, as brain plasticity is known to be affected by age;
* Presence of any DSM-5 diagnosis (other than MDD), known to be associated with prefrontal cortical dysfunction, including lifetime diagnoses of bipolar disorder, intellectual disability, or a psychotic disorder, assessed using the SCID-5 and as per investigator judgement;
* Presence of acute suicidal intent, as determined by the Scale for Suicidal Ideation (SSI);
* Contradictions to MRI or TMS (e.g., cardiac pacemaker, acoustic device, history of seizures, pregnancy), assessed using the MRI Safety Form and TMS Adult Safety Screen (TASS) and as per investigator judgement;
* Left handed, assessed using the EHI, to minimize the heterogeneity in cortical excitability and plasticity;
* Current antipsychotic, antiepileptic, or benzodiazepine use given their potential effects on cortical plasticity, as ascertained through a medication review. An exception will be made if they are taking gabapentin or pregabalin prescribed only for chronic pain, and if the dose had been stable for at least 4 weeks prior to study enrollment.

Where this trial is running

Toronto, Ontario

• Centre for Addiction and Mental Health — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Christoph Zrenner, MD

Conditions Major Depressive Disorder; TMS; TBS; iTBS; iTBS-sh; iTBS-c; iTBS-s; Sham iTBS