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

NCT ID: NCT04936126

Last Updated: 2023-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-07

Study Completion Date

2024-09-07

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Treatment Resistant Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, parallel-arm, randomized, single-blind, controlled clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The outcome assessor will remain blind to the treatment allocation

Study Groups

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Quetiapine group

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

Group Type ACTIVE_COMPARATOR

Quetiapine

Intervention Type DRUG

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

Amantadine group

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

Group Type EXPERIMENTAL

Amantadine

Intervention Type DRUG

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

Pramipexole group

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

Group Type EXPERIMENTAL

Pramipexole

Intervention Type DRUG

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

Interventions

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Quetiapine

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

Intervention Type DRUG

Amantadine

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

Intervention Type DRUG

Pramipexole

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Indian Council of Medical Research

OTHER_GOV

Sponsor Role collaborator

All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role lead

Responsible Party

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BISWA RANJAN MISHRA

Additional Professor, Department of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Debadatta Mohapatra, MD

Role: STUDY_CHAIR

All India Institute of Medical Sciences, Bhubaneswar

Locations

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All India Institute of Medical Sciences

Bhubaneswar, Odisha, India

Site Status RECRUITING

Countries

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India

Central Contacts

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Biswa R Mishra, MD, DPM

Role: CONTACT

9438884220

Rituparna Maiti, MD

Role: CONTACT

9438884191

Facility Contacts

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Biswa R Mishra, MD, DPM

Role: primary

9438884220

Rituparna Maiti, MD

Role: backup

9438884191

References

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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.

Reference Type RESULT
PMID: 27733282 (View on PubMed)

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.

Reference Type RESULT
PMID: 18058285 (View on PubMed)

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.

Reference Type RESULT
PMID: 8827185 (View on PubMed)

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.

Reference Type RESULT
PMID: 10082232 (View on PubMed)

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.

Reference Type RESULT
PMID: 27848269 (View on PubMed)

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.

Reference Type RESULT
PMID: 19752841 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40659070 (View on PubMed)

Other Identifiers

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T/EMF/Psych/19/49

Identifier Type: -

Identifier Source: org_study_id

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