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

NCT ID: NCT03126188

Last Updated: 2018-07-11

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

105 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-04-05

Study Completion Date

2018-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Depressive Episode

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Sertraline

Intervention Type DRUG

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

Dosulepin

Intervention Type DRUG

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.

Venlafaxine

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

BISWA RANJAN MISHRA

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

BISWA R MISHRA, MD

Role: PRINCIPAL_INVESTIGATOR

AIIMS, BHUBANESWAR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Dept of Psychiatry, Aiims, Bhubaneswar

Bhubaneswar, Odisha, India

Site Status

Countries

Review the countries where the study has at least one active or historical site.

India

References

Explore related publications, articles, or registry entries linked to this study.

Lee BH, Kim H, Park SH, Kim YK. Decreased plasma BDNF level in depressive patients. J Affect Disord. 2007 Aug;101(1-3):239-44. doi: 10.1016/j.jad.2006.11.005. Epub 2006 Dec 13.

Reference Type RESULT
PMID: 17173978 (View on PubMed)

Jiang C, Salton SR. The Role of Neurotrophins in Major Depressive Disorder. Transl Neurosci. 2013 Mar 1;4(1):46-58. doi: 10.2478/s13380-013-0103-8.

Reference Type RESULT
PMID: 23691270 (View on PubMed)

Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001 Aug 15;50(4):260-5. doi: 10.1016/s0006-3223(01)01083-6.

Reference Type RESULT
PMID: 11522260 (View on PubMed)

Chen YW, Lin PY, Tu KY, Cheng YS, Wu CK, Tseng PT. Significantly lower nerve growth factor levels in patients with major depressive disorder than in healthy subjects: a meta-analysis and systematic review. Neuropsychiatr Dis Treat. 2015 Apr 1;11:925-33. doi: 10.2147/NDT.S81432. eCollection 2015.

Reference Type RESULT
PMID: 25897228 (View on PubMed)

Liu X, Zhang T, He S, Hong B, Peng D, Su H, Li F, Tang Y, Lin Z, Fang Y, Jiang K. Nerve growth factor variations in patients with mood disorders: no changes in eight weeks of clinical treatment. Neuropsychiatr Dis Treat. 2014 May 15;10:835-40. doi: 10.2147/NDT.S62741. eCollection 2014.

Reference Type RESULT
PMID: 24868159 (View on PubMed)

Hock C, Heese K, Muller-Spahn F, Huber P, Riesen W, Nitsch RM, Otten U. Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression. Mol Psychiatry. 2000 Sep;5(5):510-3. doi: 10.1038/sj.mp.4000743.

Reference Type RESULT
PMID: 11032384 (View on PubMed)

Loch AA, Zanetti MV, de Sousa RT, Chaim TM, Serpa MH, Gattaz WF, Teixeira AL, Machado-Vieira R. Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jan 2;56:243-6. doi: 10.1016/j.pnpbp.2014.09.014. Epub 2014 Oct 5.

Reference Type RESULT
PMID: 25290636 (View on PubMed)

Walz JC, Magalhaes PV, Giglio LM, Cunha AB, Stertz L, Fries GR, Andreazza AC, Kapczinski F. Increased serum neurotrophin-4/5 levels in bipolar disorder. J Psychiatr Res. 2009 Apr;43(7):721-3. doi: 10.1016/j.jpsychires.2008.10.005. Epub 2008 Dec 10.

Reference Type RESULT
PMID: 19081579 (View on PubMed)

Barbosa IG, Morato IB, Huguet RB, Rocha FL, Machado-Vieira R, Teixeira AL. Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania. Braz J Psychiatry. 2014 Oct-Dec;36(4):340-3. doi: 10.1590/1516-4446-2014-1380. Epub 2014 Jul 29.

Reference Type RESULT
PMID: 25076171 (View on PubMed)

Williams JB, Kobak KA. Development and reliability of a structured interview guide for the Montgomery Asberg Depression Rating Scale (SIGMA). Br J Psychiatry. 2008 Jan;192(1):52-8. doi: 10.1192/bjp.bp.106.032532.

Reference Type RESULT
PMID: 18174510 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

T/IM-F/Psych/15/20

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

SSRIs vs. TCAs for Depression in ALS Patients
NCT02851914 COMPLETED EARLY_PHASE1