Introduction
Several studies have shown that transcranial magnetic stimulation (TMS) is effective in patients with treatment-resistant depression (TRD). TMS is a non-invasive form of treatment where the brain is stimulated by a magnetic field through a coil, which is placed in a specific place close to the patient's head while the patient sits and relaxes. The treatment does not require anesthesia and is usually well tolerated. The disadvantage is that it must be repeated daily for 20 to 30 days to achieve the optimal effect.
Recently, a research team from Stanford University (US) has published the results of a special TMS treatment (the SAINT protocol). It differs from classic TMS in that it uses TMS of the intermittent theta burst stimulation (iTBS) type, is more intensive and the entire treatment series can be shortened to 5 days. That is the patient starts treatment on Monday morning, and if it works, the patient is free of depressive symptoms by Friday evening.
In addition, the patient's brain is scanned with MRI before the treatment in order to locate the stimulation site in the brain more precisely. The study has demonstrated a very good effect of the SAINT protocol in patients with TRD compared to the control group, and the treatment was reasonably well tolerated. Results of this study are promising, but they need to be confirmed in independent groups.
There is also a need for further research into improving the TMS technique so that it becomes more effective with as few side effects as possible. This applies, among other things, to about adapting the stimulation parameters and choosing the place in the brain to be stimulated as precisely as possible. There is also a need to better understand the neurobiological mechanisms of the antidepressant effect of TMS.​

Method
In the COMPACT study, we will include patients with TRD who have not benefited from treatment with at least two different types of antidepressant medication.
The study is randomized, placebo-controlled and double-blind, i.e. that both patients and therapists do not know who is receiving TMS treatment.
The patients are divided into three groups, two of which will receive TMS of two different brain areas, respectively. dorsolateral prefrontal cortex (DLPFC), which is the stimulation site that is usually stimulated in depression and inferior parietal cortex (IPC), which is a new stimulation site that is being investigated in the COMPACT study, as it is associated with depression according to MRI studies. The last group will receive placebo (sham stimulation).
The stimulation lasts 5 hours a day over 5 days and uses iTBS with high frequency (50-200 Hz).
The brain's electrical activity is measured with electroencephalography (EEG) before, during and after the treatment.
The patients will also receive an MRI scan, incl. functional MRI (fMR) of the brain before and after the treatment to examine the effect on the brain network.
In order to examine the brain's reward system, during the scan the patients will solve tasks where they can win money.
The effect on depressive symptoms is assessed respectively 3 days and 4 weeks after treatment.

The healthy group will receive one day of stimulation according to the COMPACT protocol, have an MRI scan before the treatment and be monitored with EEG.

Researcher: PhD student, MD Iman Badr El-Amin Ibrahim
Supervisor: Professor, MD Poul Videbech 
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