Introduction:Major depressive disorder (MDD) is among the most prevalent disabling diseases, affecting millions of people around the world.^[1]Major depression is generally diagnosed when a persistent and un-reactive low mood and loss of all interest and pleasure are accompanied by a range of symptoms including appetite loss, insomnia, fatigue, loss of energy, poor concentration, psychomotor symptoms, inappropriate guilt and morbid thoughts of death .

REVIEW OF LITERATURE:

Major depression is one of the  leading cause of burden among all diseases of humankind, after lower respiratory infections and HIV/AIDS.MDD , a complex and inhomogeneous illness with an etiopathogenesis  is multifactorial based upon psychological, biological, genetic and social level.MDD also characterized by altered emotion processing and deficits in cognitive control.Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) which has predominantly been evaluated in the treatment of major depression.  . Sertraline, is one of the oldest antidepressants &most efficacious treatment for depression.Sertraline,selective serotonin reuptake inhibitors (SSRI), exerts its antidepressant activity by inhibiting the reuptake of 5-hydroxytryptamine (5-HT, serotonin) in the central nervous system, without critical effects on other neurotransmitter reuptake system,has large volumes of distribution and are highly bound to plasma proteins

Many recent investigations have suggested that the 5HTTLPR polymorphism has a role to play in human depression.Short variant has been reported to be associated with a poorer response to various antidepressant treatments^.By attenuating the impact of life events, the s allele is believed to exercise both a direct and indirect effect on the severity of depression. It has also been reported recently that the serotonin transporter is allosterically modulated by some SSRIs.Influence of a functional polymorphisim within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression.

Aim of the study and its rationale                                                                           

To evaluate the response to treatment with anti-depressant drug sertraline and mirtazapine on Beck’s depression inventory scale and to see their link with serotonin transporter gene polymorphism.

Objectives:: Primary objective:(1) To study and evaluate the response to treatment with sertraline and mirtazapine in patient of major depressive disorder ( MDD) based on pre &post treatment standard clinical parameter(Beck depression inventory scale )

Secondary objectives::(1)To study the distribution of serotonin transporter gene polymorphism in patients of MDD treated with the prescribed drugs

(2)To  study the association of drug response with genotypic distribution for serotonin transporter gene polymorphism.

(3)To record adverse effects of the prescribed drugs ,if any.

Method:Clinical diagnosis ofMDD will be made after taking detailed psychiatry history and examination under supervision of qualified psychiatrist.These patient who fulfill the inclusion criteria and sign the informed consent will be recruited. 2 Groups of 40 subjects each will be

assigned to a six week trial of Sertraline and Mirtazapine respectively. Clinical evaluation will be done with the help of Beck’s depression inventory scale at baseline and six weeks.

Outcome measures :Clinical evaluation: Remission : reduction in B.D.I score.

Incidence of adverse event           

Biochemical evaluation: Association of SERT gene with depression.

Statistical analysis:Results will be presented as mean ± standard deviation. Repeated measure Analysis of variance (ANOVA) followed by post hoc TUKEY’S TEST will be used to compare the groups for depression score.P value <0.05 will be considered as significant. CHI SQUARE test /Fisher’s exact shall be used to find the association between treatment group and genotypes.The analysis will be carried out using SPSS version 20 software package.

Risk/Benefits

The is no potential risk to the participants due to the procedures carried out in the research.There may not be any direct benefit to the society at this stage of the research,but the research result may benefit the scientific community in better understanding and better management of the disease.