The Principal Investigator left the institution, resulting in the inability to maintain necessary conditions for study continuation. Sufficient data were collected for scientific analysis, but not all planned data were obtained.

The investigators aim to conduct a single-arm open-label clinical trial, meaning that the investigators will be administering a treatment protocol to one group of patients, where no information is withheld from trial participants.

The treatment being researched will consist of a rTMS/tDCS combined 30-session protocol, consisting of 15 rTMS sessions every other day alternating with 15 tDCS at-home treatments. Treatment sessions will occur from Monday to Friday.

rTMS (Repetitive Transcranial Magnetic Stimulation) is a non-invasive physical treatment, which uses pulsing magnetic fields to activate or suppress the brain centres associated with medical and psychiatric disorders, thus treating the brain circuits involved in the patient's condition. tDCS (transcranial direct current stimulation) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head.

The investigators aim to recruit 40 patients with difficult to treat unipolar depression. Patients will be selected among the referrals to the psychiatry department in Gødstrup and to the psychiatry department in Randers.

rTMS treatment will be administered by the experienced nurses of the rTMS clinic of each department. The TMS treatment will profit from ongoing supervision by the Clinical Directors of each rTMS clinic. tDCS will be performed at home by the patients.

The study itself will last 30 days per patient, where rTMS will be administered on odd numbered days (study day 1, 3, 5, 7, ..29) and tDCS on even numbered days (study day 2, 4, 6, 8, … 30). All patients will start with rTMS and finish with home-based tDCS treatment. Both rTMS and tDCS treatments will be administered during working days, from Monday to Friday. The trial itself is expected to last no more than two years.

The goal of this study then is to examine the effectiveness of this combined neuromodulation intervention, which has the advantage of reducing the attendance requirements for TMS treatment by 50%.

Inclusion Criteria:

• Male or female, between 22 and 80 years of age.
• Able to provide informed consent.
• Primary diagnosis of depressive episode (F32) or recurrent depressive disorder (F33), according to International Classification of Diseases 10th Revision (ICD-10).
• Simultaneous fulfillment of diagnostic criteria for Major Depressive Disorder (MDD) and currently experiencing a Major Depressive Episode (MDE), according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
• Currently experiencing moderate to severe depressive episodes (scores ≥20 on the 17-item Hamilton Depression Rating Scale [HAM-D 17]).

Exclusion Criteria:

• Primary psychiatric diagnosis other than single episode depressive disorder or recurrent depressive disorder.
• History of schizophrenia or schizoaffective disorders.
• Any history of psychotic symptoms in the current or previous depressive episodes.
• History of obsessive-compulsive disorder.
• History of autism spectrum disorder.
• History of intractable migraine.
• Clinical conditions that would increase risks associated with receiving high-dose iTBS.
• Cochlear implants.
• Epilepsy.
• Pacemakers.
• Presence of metal in the head, especially of a ferromagnetic type.
• Presence of magnetically controlled implantable devices.
• Current drug misuse (F10-F19).
• History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.
• Current (or chronic) use of opiates.
• Prior nonresponse to rTMS.
• Prior nonresponse to Electroconvulsive Therapy (ECT).
• Female that is pregnant or breastfeeding.
• Female with a positive pregnancy test at participation.
• History of psychosurgery for depression.
• Damage to- or diseases of the skin, which affects the scalp. E.g. Psoriasis or open wounds.
• No changes in psychotropic medication during the study will be allowed, with the exception of the ones due to intolerability.