Worldwide, there is high prevalence of depressive disorder. Pharmacological treatment strategies to manage depression are limited by effectiveness as well as tolerability issues apart from the late onset of action. Extent of antidepressant medication response often differs with individual variation and surrogate markers predicting non-response at the earliest possible time are needed to avoid leaving patients under an inefficient medication/ treatment. 

Ketamine has been envisaged as bringing about early response in depression particularly for suicidal ideation. However, few randomized trials of oral ketamine have been conducted and there are none from India. Suicide risk is high in depression, early response to treatment is warranted. Ketamine has been envisaged as bringing about early response in depression particularly for suicidal ideation. Only few randomized trials of oral ketamine have been conducted.

Methods that objectively map effect of current flow directly in the brain through functional neuroimaging signal changes after a series of ketamine sessions may help us understand how ketamine works, how it can be optimized, and if it can be used as an effective intervention for early reduction of depressive symptoms particularly for suicidal ideation.

Use of fNIRS/qEEG can depict the cortical activity associated with the changes in symptoms of depression. Levels of BDNF have been found to be low in depression that improves with response to treatment. These changes can also provide guidance towards the potential mechanism of action for ketamine.

Consultants and Senior Residents in the outpatient department (OPD) and inpatient department (IPD) of Psychiatry, AIIMS, New Delhi shall be requested to refer all the patients with depression. Out of the referred patients, those with HAMD score >17 (moderate to severe depression) will be chosen by a purposive method for participation in the study. Diagnosis of severe depression will be confirmed using DSM-5 criteria by clinical interview and participants fulfilling the inclusion and exclusion criteria will be recruited. Participants will be screened for psychiatric comorbidities using clinical interview. Physical, neurological and substance use comorbidity as well as pregnancy/lactation will be ruled out by history and clinical examination. Written consent will be taken prior to participation in the study. Healthy controls will also be recruited similarly from the outpatient department (OPD) and inpatient department (IPD) of Psychiatry, AIIMS, New Delhi, who are meeting inclusion and exclusion criteria. Baseline assessment will be done within 2 days of assessments by sociodemographic and clinical data using semi structured datasheet and outcome parameters will be assessed by namely HAMD, HAMA, MSSI. For other outcome parameters, serum BDNF levels, fNIRS and qEEG would also be done. Both active and placebo groups will be reassessed at 1 and 2 weeks (±2-3 days) using above mentioned parameters.