In recent years, research on the effectiveness of transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (RTD) has been steadily increasing. The aim of this study was to examine the effectiveness of accelerated unilateral application of two different forms of theta burst stimulation (TBU), a variation of repetitive TMU (rTMS)-intermittent TBU (iTBU) and continuous TBU (cTBU)-in TDD patients. The study aimed to compare the advantages of iTBU and cTBU protocols on depression, suicidal thoughts, anxiety levels, sleep disturbances, cognitive performance, and overall functioning following a two-week intensive treatment period and a 12-week follow-up period.

Major depressive disorder (MDD) is the most common form of mood disorders that is frequently encountered in the society, has high recurrence and chronicity rates, and can lead to significant physical, cognitive, and psychosocial dysfunction in individuals. Although there is no single universally accepted definition for treatment-resistant depression (TRD), one of the most frequently used definitions is "failure to respond to at least two different antidepressant treatments for a sufficient duration and at an appropriate dose." Repetitive transcranial magnetic stimulation (rTMS) applied to the left and/or right dorsolateral prefrontal cortex (DLPFC) stands out as an alternative treatment approach in patients with TRD. One of these methods, theta-burst stimulation (TBS), is a non-invasive neuromodulation method approved by the US Food and Drug Administration (FDA) for treatment-resistant depression. Current methodological advances have enabled current TBS protocols to; Therapeutic efficacy can be enhanced by applying sessions multiple times a day, increasing the stimulation dose, and more precisely targeting the bilateral DLPFC. In addition to intermittent TBS (iTBS), continuous TBS (cTBS) protocols applied to the right DLPFC have also been reported to offer therapeutic potential in patients with TDD. Several studies have demonstrated that protocols consisting of 1,800 pulses produce lasting changes in cortical excitability and effectively trigger targeted neuroplastic mechanisms.

The study was planned to be conducted with patients who presented to the Atatürk University Faculty of Medicine, Department of Psychiatry Outpatient Clinic and were diagnosed with major depressive disorder (MDD) according to the American Psychiatric Association's DSM-5 diagnostic criteria. Participants were randomly assigned to two groups. In this single-blind, parallel study, one group was scheduled to receive a total of 50 sessions of iTBS to the left dorsolateral prefrontal cortex (left-DLPFC), while the other group received 50 sessions of cTBS to the right-DLPFC.

Clinical assessments of patients will be conducted at baseline, mid-treatment, at the end of treatment, and at weeks 2, 4, 8, and 12 post-treatment. Depressive symptoms will be measured with the HAM-D and MADRS, anxiety with the Hamilton Anxiety Rating Scale (HAM-A), sleep disturbances with the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), cognitive functions with the Montreal Cognitive Assessment Scale (MoCA), and functioning with the Brief Functioning Assessment Scale (BFAS). Participants were expected to maintain their current psychotropic medication at stable doses throughout the study.

Inclusion Criteria:

1. 18 to 65 years old
2. Patients diagnosed with Major Depressive Disorder according to DSM 5 and the severity of their illness
3. Scoring 7 points or more on the Maudsley staging method
4. Having depression unresponsive to 2 different antidepressants
5. No clinical mental retardation
6. Agree to participate in the study
7. Hamilton Depression Rating Scale-17 [HDRS] score of 20 or higher
8. Montgomery Asberg Depression Rating Scale [MADRS] score of 20 or above
9. Being right hand dominant
10. Having used the same antidepressant at the same dose for the last 4 weeks

Exclusion Criteria:

1. Diagnosed with a neurological or metabolic disease that affects cognitive functions (Systemic diseases such as diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic renal failure, Parkinson's disease, multiple sclerosis, polyneuropathy, inflammatory rheumatologic disease and malignancies)
2. Having a foreign body such as a pacemaker, intracranial implant that can magnetically interact
3. Hearing and visual impairments that prevent communication
4. Unstable or acute medical conditions
5. Pregnancy or breastfeeding
6. Having a primary psychiatric disorder other than major depressive disorder
7. Being diagnosed with severe MDD with psychotic features