STUDY OBJECTIVES:
Primary Objective
• To compare the change in the severity of symptoms of depression in terms of change in HAM-D scores between the treatment groups over 8 weeks.
Secondary Objective
* To compare the change in CGI scores between the treatment groups over 8 weeks.
* To evaluate the change in serum BDNF, serum NGF levels between the treatment groups over 8 weeks.
* To detect adverse drug reactions (if any) (prescribed format for Pharmacovigilance program of India PVPI)
Study design:
This study will be a hospital-based, prospective, randomized, single-blind, controlled clinical trial in patients with unipolar depression clinically diagnosed as TRD, which will be conducted over a period of 3 years.
Study population and eligibility:
The study cohort will comprise of 150 patients with the diagnosis of unipolar treatment-resistant depression (TRD), attending the in-patient or out-patient department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar. The patient should have received adequate trials of at least two antidepressants (one of which preferably should be an SSRI) at adequate dose and duration (\> 6 weeks), with poor clinical response while on regular compliance. The patients fulfilling the criteria who are currently on Sertraline treatment (dose range = 100-200 mg/day), giving written informed consent will be recruited for the present study. The detailed history, relevant socio-demographic, and clinical data will be collected in a structured case record form (CRF).
Study Procedure and Data collection:
Baseline assessment:
At baseline, Hamilton Depression Scale (HAM-D 21 item) will be administered to determine the severity of depressive symptoms, Clinical Global Inventory (CGI) will be administered to determine the baseline severity of the illness. Serum BDNF, and NGF will be estimated by ELISA using commercially available Human ELISA kit.
Randomization:
The study cohort of 150 participants will be randomized into three treatment groups by block randomization technique (computer-generated) with 25 blocks, each block with 6 participants. The sample will be divided into 3 equal treatment groups, each group comprising of 50 patients.
Treatment Allocation:
Group 1 will receive Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment. Group 2 will receive Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment. Group 3 will serve as the control arm and receive the recommended Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment.
Follow up assessment:
The study cohort will be reassessed for the changes in HAM-D scores, CGI severity scores, Improvement score, and Efficacy index, at 4 and 8 weeks follow up. The changes in Serum BDNF and NGF will be estimated at the end of 8 weeks, to correlate with the change in the severity of depressive symptoms.
Rescue Medication:
The patient in either of the treatment arms, who are not responding to treatment or relapsing with aggravation of depressive symptoms will be switched on to Venlafaxine treatment or ECT as decided by the treating team.
Safety evaluation:
All the participants will be evaluated for any untoward side effects like insomnia, restlessness, and agitation, etc. which will be documented and informed to the institutional ethics committee.
