Comparison of Antidepressant Augmentation With Amantadine vs Pramipexole vs Quetiapine in Treatment Resistant Depression

NCT04936126 | Unknown Phase 4

• 1 other identifier: T/EMF/Psych/19/49
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Treatment Resistant Depression

Keywords

Treatment Resistant Depression; Augmentation; Amantadine; Pramipexole; BDNF; NGF

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Scale scores

  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 Outcomes (4)

• Clinical Global Impression scores

  8 weeks

• Serum Brain Derived Neurotrophic Factor

  8 weeks

• Serum Nerve Growth Factor

  8 week

• Rescue Medications

  8 weeks

Study Arms (3)

Quetiapine group

ACTIVE COMPARATOR

Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment.

Drug: Quetiapine

Amantadine group

EXPERIMENTAL

Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment

Drug: Amantadine

Pramipexole group

EXPERIMENTAL

Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment

Drug: Pramipexole

Interventions

Quetiapine DRUG

Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment for the study period

Quetiapine group

Amantadine DRUG

Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment for the study period

Amantadine group

Pramipexole DRUG

Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment for the study period

Pramipexole group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead
• Indian Council of Medical Research: collaborator

Study Sites (1)

All India Institute of Medical Sciences

Bhubaneswar, Odisha, 751019, India

RECRUITING

Related Publications (7)

• GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6.

  PMID: 27733282 RESULT

• Kennedy SH, Giacobbe P. Treatment resistant depression--advances in somatic therapies. Ann Clin Psychiatry. 2007 Oct-Dec;19(4):279-87. doi: 10.1080/10401230701675222.

  PMID: 18058285 RESULT

• Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996 Jun;19(2):179-200. doi: 10.1016/s0193-953x(05)70283-5.

  PMID: 8827185 RESULT

• Souery D, Amsterdam J, de Montigny C, Lecrubier Y, Montgomery S, Lipp O, Racagni G, Zohar J, Mendlewicz J. Treatment resistant depression: methodological overview and operational criteria. Eur Neuropsychopharmacol. 1999 Jan;9(1-2):83-91. doi: 10.1016/s0924-977x(98)00004-2.

  PMID: 10082232 RESULT

• Dold M, Kasper S. Evidence-based pharmacotherapy of treatment-resistant unipolar depression. Int J Psychiatry Clin Pract. 2017 Mar;21(1):13-23. doi: 10.1080/13651501.2016.1248852. Epub 2016 Nov 16.

  PMID: 27848269 RESULT

• Fleurence R, Williamson R, Jing Y, Kim E, Tran QV, Pikalov AS, Thase ME. A systematic review of augmentation strategies for patients with major depressive disorder. Psychopharmacol Bull. 2009;42(3):57-90.

  PMID: 19752841 RESULT

• Mishra BR, Mohapatra D, Biswas T, Mishra A, Panigrahi S, Maiti R. Comparative efficacy of antidepressant augmentation with amantadine vs pramipexole in treatment-resistant unipolar depression: A randomised controlled trial. J Affect Disord. 2025 Dec 1;390:119891. doi: 10.1016/j.jad.2025.119891. Epub 2025 Jul 13.

  PMID: 40659070 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Quetiapine Fumarate; Amantadine; Pramipexole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 2-Ring

Study Officials

• Debadatta Mohapatra, MD

  All India Institute of Medical Sciences, Bhubaneswar

  STUDY CHAIR

Central Study Contacts

Biswa R Mishra, MD, DPM

CONTACT

9438884220; brm1678@gmail.com

Rituparna Maiti, MD

CONTACT

9438884191; rituparnamaiti@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The outcome assessor will remain blind to the treatment allocation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor, Department of Psychiatry

Model Details: Prospective, parallel-arm, randomized, single-blind, controlled clinical trial

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 23, 2021
• Study Start: August 7, 2021
• Primary Completion: July 7, 2024
• Study Completion: September 7, 2024
• Last Updated: August 22, 2023

Record last verified: 2023-08

Locations

IN (1)