Comparison of Antidepressant Augmentation With Amantadine vs Pramipexole vs Quetiapine in Treatment Resistant Depression (APQ-TRD)

August 21, 2023 updated by: BISWA RANJAN MISHRA, All India Institute of Medical Sciences, Bhubaneswar

Comparative Efficacy of Antidepressant Augmentation With Amantadine vs Pramipexole vs Quetiapine in Treatment-resistant Unipolar Depression: A Randomized Controlled Trial.

The present study has been designed to compare the efficacy and safety of augmentation of SSRIs with Amantadine vs Pramipexole vs the recommended Quetiapine augmentation in Treatment-Resistant Depression (TRD) and correlate the changes in depression scores with changes in the serum levels of Brain-derived neurotrophic factor (BDNF) and Nerve growth factor (NGF).

The proposed study will be a prospective, randomized, single-blind, controlled clinical trial in patients with TRD and will be conducted over a period of 2 years. The study cohort will comprise 150 patients with unipolar depression clinically diagnosed as TRD, who are currently on Sertraline treatment (dose range = 100-200 mg/day). 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. The sample will be divided into 3 equal treatment groups by block randomization technique, each group comprising of 50 patients.

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.

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 severity of depressive symptoms. All the participants will be evaluated for any untoward side effects in a prescribed format for the Pharmacovigilance program of India (PVPI). 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 Electro-convulsive therapy (ECT) as decided by the treating team.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Orissa
      • Bhubaneswar, Orissa, India, 751019
        • Recruiting
        • All India Institute of Medical Sciences
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Debadatta Mohapatra, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients with unipolar depression clinically diagnosed as TRD, who are currently on Sertraline treatment (dose range = 100-200 mg/day)
  2. Patients aged 18-60 years of either sex

Exclusion Criteria:

  1. Patients with Bipolar affective disorder
  2. Patient with TRD on antidepressants other than Sertraline
  3. History of psychoactive substance abuse or dependence
  4. Co-morbid psychiatric, major medical, or neurological disorders
  5. History of organicity or significant head injury
  6. Pregnant and lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Quetiapine group
Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment.
Drug: Quetiapine
Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment for the study period
Experimental: Amantadine group
Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment
Drug: Amantadine
Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment for the study period
Experimental: Pramipexole group
Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment
Drug: Pramipexole
Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment for the study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Depression Scale scores
Time Frame: 8 weeks
Change in Hamilton Depression Scale scores 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression Higher scores indicating higher severity of depression
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression scores
Time Frame: 8 weeks
Change in Clinical Global Impression scores CGI-S severity scores range from 1-7, with higher scores indicating greater severity of illness CGI-I Improvement score range from 1-7, with lower scores indicating improvement and higher scores indicating worsening
8 weeks
Serum Brain Derived Neurotrophic Factor
Time Frame: 8 weeks
Change in Serum Brain Derived Neurotrophic Factor levels
8 weeks
Serum Nerve Growth Factor
Time Frame: 8 week
Change in Serum Nerve Growth Factor
8 week
Rescue Medications
Time Frame: 8 weeks
Number of patients in the Rescue medication group
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Collaborators

Indian Council of Medical Research

Investigators

  • Study Chair: Debadatta Mohapatra, MD, All India Institute of Medical Sciences, Bhubaneswar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2021

Primary Completion (Estimated)

July 7, 2024

Study Completion (Estimated)

September 7, 2024

Study Registration Dates

First Submitted

June 14, 2021

First Submitted That Met QC Criteria

June 14, 2021

First Posted (Actual)

June 23, 2021

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 21, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T/EMF/Psych/19/49

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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