COpenhagen Magnetic Personalized Accelerated Brain Circuit Therapy for Treatment Resistant Depression

Summary

The CoMPACT trial is a randomized double-blinded sham-controlled study aimed at testing a novel accelerated and personalized transcranial Magnetic Stimulation (TMS) treatment for patients with Treatment Resistant Depression (TRD). CoMPACT consists of 25 sessions of intermittent theta-burst transcranial stimulation (iTBS) consisting of high inter-pulse frequency administered five times daily over five consecutive days. The trial will include 78 patients with TRD who will be randomly assigned to one of three groups: * Group 1: Real CoMPACT targeting the left dorsolateral prefrontal cortex (DLPFC). * Group 2: Real CoMPACT targeting a novel site, the left inferior parietal lobule (IPL). * Group 3: Sham CoMPACT targeting the left DLPFC (50%, Group 3a) or left IPL (50%, Group 3b). The hypothesis is that real prefrontal or parietal CoMPACT targeting will significantly alleviate depression symptoms compared to sham targeting, without compromising safety, feasibility, or tolerability. The trial incorporates a personalized approach, using electrical field (E-field) modeling based on individual structural brain scans to tailor and standardize iTBS, ensuring accurate targeting of cortical volume and consistent induced electrical field strength. To delineate the treatment mechanism of action at the brain network level, multi brain mapping models will be implemented. Electroencephalography (EEG) records of spontaneous and TMS-evoked electrical brain activity will be obtained before, during, and after iTBS sessions to understand how the high frequency burst protocol functionally engages the stimulated cortex. Structural and functional brain MRI before and after the treatment will be used to study changes in depression-related brain networks. This will offer key insights into how CoMPACT affects depression-related brain networks and may identify neuroimaging markers for predicting treatment response, and thus informing future TBS treatments for TRD.

Eligibility

Inclusion criteria:

* Age range between 18 and 95 years
* In- or outpatients with a moderate to severe single episode or periodic MDD according to ICD-10, verified by a M.I.N.I. interview.
* Major Depression Inventory (self-rapport) score higher than 25.
* Lacking or insufficient effect of at least two drug trials from two distinct classes, e.g., SSRI, SNRI, TCA, or MAO-inhibitors, used in the current episode, with adequate dose and duration as judged by the investigator.
* Duration of the current episode must be longer than 2 months but shorter than 4 years, as judged by the investigator.

Exclusion criteria:

* History of neurologic disease affecting the brain, including dementia and epilepsy
* Schizophrenia or any other psychotic disorder except for psychotic depression
* Head trauma causing more than 5 minutes loss of consciousness
* Suicidal or psychotic symptoms making the transport of participants hazardous
* Any form of compulsory admission or treatment within the past three months
* Treatment with ECT in the current depressive episode
* Non-responders to TBS treatment within the current episode
* Current harmful use or dependency of substances according to ICD-10 and interfering with outcome evaluation as judged by investigator's discretion.
* High risk of non-adherence as judged by investigators discretion
* Medical and psychiatric conditions interfering with study outcome and safety as judged by investigator's discretion.
* Female participants of childbearing age must not be pregnant or breast feeding, and they must use contraception during the trial.
* One of the prime contra-indications for MRI, including severe claustrophobia (see Appendix 08.05)
* One of the prime contra-indications for TMS and persons with electrically, magnetically, or mechanically activated implants or with metal or magnetic pieces in their head (see Appendix 08.04)
* Patients who do not wish to be informed about MRI or EEG findings, which may have clinical relevance.

Conditions2

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