Efficacy of Mirtazapine in Major Depressive Disorder With Insomnia

Background: Mirtazapine is an atypical antidepressant acts by increasing noradrenergic and serotonergic neurotransmission. It inhibits presynaptic adrenergic alpha-2 receptor along with inhibition of postsynaptic serotonergic 5-HT2 and 5-HT3 receptors and histamine (H1) receptor (Jilani et al., 2022). It was approved by FDA in 1996 for treating moderate and severe depression; but it also has sedative, antiemetic, anxiolytic, and appetite stimulant effects and for these prescribed in many other psychiatric disorders (Nutt, 2002). Because of its efficacy, safety and tolerability, it is one of the drugs recommended by NICE to consider as first-choice in treating depression (Middleton et al., 2005).

A depressive episode is characterized by a period of depressed mood or diminished interest in activities occurring most of the day, nearly every day during a period lasting at least two weeks accompanied by other symptoms such as difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue. There have never been any prior manic, hypomanic, or mixed episodes, which would indicate the presence of a bipolar disorder (ICD-11, 2019).

Around 6.7% of adult population in Bangladesh suffers from depressive disorders (NIMH, 2019). However, no interventional study has yet been carried out to see efficacy of different antidepressants in this population. As one of the frequently observed features of depression is insomnia, mirtazapine could be a good choice in these cases. This study intends to assess the efficacy of mirtazapine in major depressive disorder when the patients also present with insomnia.

General objective To assess the efficacy of mirtazapine in reducing depression with insomnia symptoms in patients with major depressive disorder (MDD) with insomnia.

Specific objectives

1. To assess the efficacy of mirtazapine in reducing depressive symptoms in patients with MDD with insomnia. 2. To assess the efficacy of mirtazapine in reducing insomnia symptoms in patients with MDD with insomnia. 3. To compare the quality of life in patients with MDD before and after introducing mirtazapine. 4. To assess the side-effects experienced by trial patients.

Methods: This will be a single center, prospective, open label, quasi-experimental pre-post intervention trial in MDD patients with insomnia. The study will be conducted at National Institute of Mental Health (NIMH), Bangladesh over a period of 8 months. A total of 135 MDD patients with insomnia who fulfill the selection criteria will be conveniently selected for the study. Following enrollment and baseline assessment patients will be prescribed mirtazapine at 15-30 mg/day. Depending on the response, doses will be adjusted after two weeks and might be titrated up to 45 mg/day.