Study of the Effect of Antidepressant Drugs on Neurotrophic Factors in Patients With Depression
Condition: Depressive Episode
MeSH terms: Depression
Study type: Observational

Summary: 
      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: 
      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.
    

Intervention name(s): Sertraline; Dosulepin; Venlafaxine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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 MeSH terms: Sertraline; Venlafaxine Hydrochloride
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients diagnosed with depression with or without somatic syndrome attending the
        outpatient department of Psychiatry, AIIMS, Bhubaneswar.