Study of the Effect of Antidepressant Drugs on Neurotrophic Factors in Patients With Depression

July 9, 2018 updated by: BISWA RANJAN MISHRA, All India Institute of Medical Sciences, Bhubaneswar
The aim of the present study will be to observe the changes in the NTs like Nerve growth factor, Neurotrophin-3, and Neurotrophin-4 in patients with depression and study the effect of various antidepressants like Sertraline (SSRI), Dosulepin (TCA), and Venlafaxine (SNRI) on their levels.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Depression is one of the common psychiatric disorders, with a worldwide prevalence of around 16·2%, with multifactorial causality, but partially unknown pathophysiology. Depression likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes.

In context to Neurotropic hypothesis, in depression there is reduction in Neurotrophins (NTs), which impairs the pruning of the neural network, alters neural plasticity, and impacts negatively on the structural and functional processes within the limbic system. NTs in general and Brain Derived Neurotrophic Factor (BDNF) in particular modulate depressive behavior and the response to antidepressant treatment, in part through the regulation of synaptic plasticity, synaptogenesis, and neurogenesis. Major neurotrophins like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) have been identified in context to nervous system functioning.

Previous studies have consistently proved the reduction in BDNF levels in patients with depression and antidepressants were found to increase BDNF protein levels with re-establishment of normative cortical networks in different areas of hippocampus. Recent studies have provided important links between the neurobiological characteristics of depression and NGF. Animal studies have revealed decreasing levels of NGF in specific brain areas of different mouse models, including anxiety vulnerability, stress-induced illness, and learned helplessness. In relation to the patients with depression, NGF has been recognized as an important factor in modulating their altered or dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have compared the differences in peripheral NGF levels in patients with depression and healthy controls, others have investigated the effect of different treatments on their levels. The results have been conflicting in relation to NGF levels results before and after antidepressant treatment in patients with depression, thus, necessitating the need for further research in this area.

Studies related to NT-3 levels in unipolar depression is limited, when researchers have reported of increased CSF levels of NT-3 in elderly depressed patients and increased serum NT-3 levels in the depressive phase of Bipolar disorder. Lower level of neurotrophins like BDNF, but higher level of NT-3, have been found in depressed patients with schizophrenia. NT-4 has been a potential candidate neurotropic factor for research in patients with mood disorder. Studies have reported of increased serum NT-4 levels in the depressive phase of Bipolar disorder, when others have found the increase in serum NT-4 levels in both the depressive and manic phases of the illness. Contrastingly, studies have also found reduction in NT-4 levels in the manic phase of Bipolar disorder.

The literature search clearly reveals the lack of studies or inconsistent findings in relation to the role of major NTs like NGF, Neurotrophin-3, and Neurotrophin-4 in unipolar depression. It will be worth studying the changes in these NTs in depression and the effect of various antidepressants on their levels, this can help us in understanding the caveats in pathophysiology of depression better, which can have future treatment implications.

The aim of the present study will be to observe the changes in the NTs like Nerve growth factor, Neurotrophin-3, and Neurotrophin-4 in patients with depression and study the effect of various antidepressants like Sertraline (SSRI), Dosulepin (TCA), and Venlafaxine (SNRI) on their levels.

Study Type

Observational

Enrollment (Actual)

105

Contacts and Locations

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

Study Locations

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751019
        • Dept of Psychiatry, Aiims, Bhubaneswar

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients diagnosed with depression with or without somatic syndrome attending the outpatient department of Psychiatry, AIIMS, Bhubaneswar.

Description

Inclusion Criteria:

  • Patients with the diagnosis of Depressive episode (Single episode or recurrent) (by ICD-10 DCR) without psychotic symptoms.
  • Patients aged 18-65 years, of either sex.
  • Patients with baseline score > 7 on the Montgomery-Asberg Depression Rating Scale (MADRS).
  • Treatment naïve or patients who had not taken any treatment for at least 4 weeks before inclusion.

Exclusion Criteria:

  • Patients with Depressive episode (by ICD-10 DCR) with psychotic symptoms.
  • Patients with Bipolar depression or with Persistent mood disorder (Dysthymia/ Cyclothymia)
  • Patients who are already under treatment for the presenting conditions.
  • Previous history of refractoriness to SSRI, TCA, or SNRI.
  • Patients with comorbid substance abuse or history of organicity
  • Patients with history of major medical or neurological illness.
  • Pregnant and nursing 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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Sertraline group
Mild and Moderate depressive episode without somatic syndrome who are treated with Sertraline. Tab. Sertraline 50 mg/day, which will be optimized to 75mg/day after 2 weeks if required, and maintained on the same dose for a minimum period of 6 weeks.
Drug: Sertraline
Tab. Sertraline 50 mg/day, which will be optimized to 75mg/day after 2 weeks if required, and maintained on the same dose for a minimum period of 6 weeks.
Dosulepin group
Mild and Moderate depressive episode with somatic syndrome who were treated with Dosulepin. Tab. Dosulepin 25mg/day, which will be gradually hiked up to 75mg/day over 2 weeks
Drug: Dosulepin
Tab. Dosulepin 25mg/day, which will be gradually hiked up to 75mg/day over 2 weeks,and the patients will be continued on the same dose for a minimum period of 6 weeks.
Venlafaxine group
Severe depressive episode without psychotic symptoms who were treated with Venlafaxine. Tab. Venlafaxine 75mg/day, which will be hiked to 112.5 mg/day after 2 weeks, and the patients will be continued on the same dose for a minimum period of 6 weeks.
Drug: Venlafaxine
Tab. Venlafaxine 75mg/day, which will be hiked to 112.5 mg/day after 2 weeks, and the patients will be continued on the same dose for a minimum period of 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum nerve growth factor from baseline over 6 weeks
Time Frame: Baseline and 6 weeks
ELISA
Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum neurotrophin 3 from baseline over 6 weeks
Time Frame: Baseline and 6 weeks
ELISA
Baseline and 6 weeks
Change in serum neurotrophin 4 from baseline over 6 weeks
Time Frame: Baseline and 6 weeks
ELISA
Baseline and 6 weeks
Change in severity of symptoms of depression from baseline over 6 weeks
Time Frame: Baseline and 6 weeks
Montgomery-Åsberg Depression Rating Scale
Baseline and 6 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

Investigators

  • Principal Investigator: BISWA R MISHRA, MD, AIIMS, 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)

April 5, 2017

Primary Completion (Actual)

December 31, 2017

Study Completion (Actual)

February 28, 2018

Study Registration Dates

First Submitted

April 20, 2017

First Submitted That Met QC Criteria

April 20, 2017

First Posted (Actual)

April 24, 2017

Study Record Updates

Last Update Posted (Actual)

July 11, 2018

Last Update Submitted That Met QC Criteria

July 9, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T/IM-F/Psych/15/20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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