Efficacy of combined high-definition transcranial direct current stimulation with intermittent theta burst stimualtion in treatment of major depressive disorder: a randomized sham controlled trial

Major Depressive Disorder MDD is a debilitating mood disorder characterized by persistent low mood and loss of interest for two weeks or more accompanied by sleep and appetite changes fatigue impaired concentration and suicidal thoughts. It severely impacts social occupational and personal functioning. MDD is more common in women with onset typically in early adulthood. The development of MDD is influenced by a complex interplay of genetic and environmental factors with heritability estimated at around thirty five percent. It is linked to brain abnormalities particularly in the hippocampus and networks involved in emotion regulation and cognitive control.

The National Mental Health Survey conducted during 2015 to 2016 across twelve states with thirty four thousand eight hundred and two adults found a lifetime prevalence of depressive disorders of five point two five percent. Diagnosed MDD frequently goes untreated in India. A 2024 study showed that among middle aged and older adults with depression ninety seven percent remained undiagnosed and seventy seven percent untreated with rural areas being particularly underserved.

Diagnostic criteria include the presence of at least five symptoms out of nine including either depressed mood or anhedonia. These symptoms are depressed mood either subjective or observed anhedonia or loss of interest or pleasure weight or appetite changes insomnia or hypersomnia psychomotor agitation or retardation fatigue feelings of worthlessness or excessive guilt impaired concentration and suicidal ideation. Symptoms must cause significant distress or functional impairment. The condition should not be attributable to substances or medical conditions such as hyperthyroidism. Psychotic disorders and bipolar disorder must be ruled out with no history of mania or hypomania. Specifiers include severity mild or severe presence of psychotic features melancholic or atypical features and peripartum or seasonal onset.

Non invasive brain stimulation therapies include repetitive Transcranial Magnetic Stimulation rTMS which is a non invasive brain stimulation technique using magnetic pulses. Types include single pulse paired pulse or repetitive stimulation. Theta burst stimulation involves high frequency bursts delivered at lower frequency and can be intermittent or continuous. Transcranial Direct Current Stimulation tDCS uses a weak electrical current to modulate neuronal activity through anode and cathode electrodes. Subthreshold effects alter resting membrane potentials influencing spontaneous neuronal firing and can induce lasting cortical changes beyond the stimulation period.