Interim results of efficacy of mirtazapine in MDD with insomnia

1. MIRTAZAPINE TRIAL
Interim Report

2. Efficacy of Mirtazapine in Major Depressive Disorder
with Insomnia: A 6-week Pre and Post Intervention
Study

3. BACKGROUND
▪ Depressive disorders are the most common mental illnesses in adult Bangladeshi
population.
▪ Insomnia is estimated to occur in about 75% of adult patients with depression.
▪ Efficacy of antidepressants on depression with insomnia needs further evaluation.

4. MIRTAZAPINE
▪ Has antidepressant, sedative, antiemetic, anxiolytic and appetite stimulant effects.
▪ Because of its efficacy, safety and tolerability, it is one of the drugs recommended
by NICE to consider as first-choice in treating depression.

5. SPECIFIC OBJECTIVES
▪ To assess the efficacy of mirtazapine in reducing depressive symptoms in patients
with MDD with insomnia.
▪ To assess the efficacy of mirtazapine in reducing insomnia symptoms in patients
with MDD with insomnia.
▪To assess the side-effects experienced by trial patients.

6. RESEARCH QUESTIONS
1. Is mirtazapine efficacious in reducing depressive symptoms in patients of MDD
with insomnia?
2. Is mirtazapine efficacious in reducing insomnia symptoms in patients of MDD with
insomnia?

7. STUDY DESIGN
▪ It is a prospective, open-label, quasi-experimental pre-post intervention trial in
MDD patients with insomnia.

8. STUDY POPULATION
Major depressive disorder (MDD) patients with insomnia.
Calculated sample size is 135.

9. INCLUSION CRITERIA
1. Age 18–60 years
2. Diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
(DSM-5) for MDD
3. A ≥20 total score on the 17-item Hamilton depression rating scale (HDRS)
4. A ≥15 total score on the 7-item Insomnia Severity Index (ISI)
5. Considered to require antidepressant treatment based on the judgment of the consulting
psychiatrist.
6. For women – willing to abstain from conception or willing to use modern method of contraception
(she or her partner) during trial period.

10. EXCLUSION CRITERIA
1. History of use of mirtazapine in the last 3 months period
2. Pregnant or breastfeeding mother
3. At significant risk for suicide
4. Diagnosed with a primary condition including dementia as well as bipolar, obsessive–
compulsive, or eating disorders, schizophrenia, or alcohol or substance dependence except
for tobacco dependence
5. Experiencing any medical conditions judged to render the patient ineligible to participate
in the study.

11. INSTRUMENTS
▪ A Semi-structured clinical information questionnaire
▪ Hamilton Depression Rating Scale (HDRS)
▪ Insomnia Severity Index (ISI)
▪ Antidepressant Side-Effect Checklist (ASEC)

12. RESPONSE
Response is defined as reduction in
▪HDRS score of <8
▪ISI score of < 8

13. Approaching patients with MDD
Consideration of selection criteria
Consent and enrollment
HDRS, ISI score at
Day 0
Mirtazapine 15-45
mg for 42 days
Evaluation by HDRS,
ISI, ASEC at Day 14
and 42
Improved Not improved
Follow-up and
dose adjustment
at Day 14
Clinical Follow-up
over telephone on
Day 28

14. Day 0
Baseline
assessment
Starting the
treatment
Mirtazapine
15-30 mg/day
Assessment
at Day 14
Increase dose
to 30-45
mg/day if
required
Day 14 Day 28 Day 42
End of trial
assessment
Semi-
structured
questionnaire
- Clinical follow
up over
telephone
-
HDRS HDRS HDRS
ISI ISI ISI
- ASEC ASEC

15. ETHICAL ISSUES
▪ In accordance with Helsinki Declaration, Bangladesh Medical Research Council
(BMRC) and Directorate General of Drug Administration guidelines.
▪ Patients’ drug, travel and laboratory investigation cost will be provided by the
research team.

16. INVESTIGATOR AND FUNDING
▪ Principal Investigator - Dr. Mohammad Tariqul Alam
▪ This study is conceptualized and sponsored by Bangladesh Association of
Psychiatrists (BAP) with scientific support and research grant from Sun
Pharmaceutical Bangladesh Ltd.

17. LATEST UPDATES (06/08/2023)
Total patient enrolled – 53.
First follow up (14th day) completed – 49
Second follow up (28th day) completed – 33
Full trial (42 Days) completed – 11

20. CHARACTERISTICS
Characteristics Level Frequency Percentage
Age group 18-28 11 22.4
29-39 10 20.4
40-50 20 40.8
>50 8 16.3
Gender Male 17 34.7
Female 32 65.3
Residence Urban 35 71.4
Rural 13 26.5

21. CHARACTERISTICS
Characteristics Level Frequency Percentage
Occupation Housewife 25 51
Service 11 22.4
Others 13 26.6
Education (mean ± SD) 12.1 4.8
Number of episode 3.3 2.7
Duration of current
episode (months) 4.3 5.5

22. MIRTAZAPINE TRIAL
Dose Baseline 14 Day 42 Day
15 mg 47 (95.9) 19 (38.8) 27 (55.1)
30 mg 2 (4.1) 17 34.6) 10 (20.4)
45 mg - 2 (4.1) 2 (4.1)
Mean 15.6 22.5 20.3
Cell values are frequency (percentage)

23. EFFICACY IN INSOMNIA
20.6
10.7
6.8
-2
3
8
13
18
23
28
Baseline 14-Day 42-Day
Baseline – 14 Day = 9.9
Baseline – 42 Day = 13.8
14 Day – 42 Day = 3.9
P values are 0.000 for all
comparisons in repeated
measures ANOVA
Figure 1: Insomnia severity index mean score at different time points

24. EFFICACY IN DEPRESSION
26.7
16.3
10.7
0
5
10
15
20
25
30
Baseline 14-Day 42-Day
Figure 2: HDRS mean score at different time points
Baseline – 14 Day = 10.4
Baseline – 42 Day = 16
14 Day – 42 Day = 5.5
P values are 0.000 for all
comparisons in repeated
measures ANOVA

25. RESPONSE RATE
Symptom 14-Day 42-Day
Insomnia 11 (22.4) 33 (67.3)
MDD 7 (14.3) 20 (40.8)
Table: Response rate of patients at different time period
Cell values are frequency (percentage)

26. SIDE EFFECTS AT DAY 14 AND 28
Symptom Day 14 Day 28
Dry mouth
7 (14.3) 4 (8.2)
Drowsiness
7 (14.3) 9 (18.4)
Insomnia
3 (6.1) 1 (2)
Blurred vision
7 (14.3) 3 (6.1)
Headache
6 (12.2) 4 (8.2)
Constipation
4 (8.2) 1 (2)
Diarrhoea
1 (2) 2 (4.1)
Increased appetite
12 (24.5) 10 (20.4)
Decreased appetite
2 (4.1) 2 (4.1)
Nausea or vomiting
3 (6.1) 1 (2)
Problems with urination
1 (2) -
Cell values are frequency (percentage)

27. SIDE EFFECTS AT DAY 14 AND 28
Symptom Day 14 Day 28
Problems with sexual function
2 (4.1) 1 (2)
Palpitation
3 (6.1) 6 (12.2)
Feeling light headed on standing
4 (8.2) 6 (12.2)
Feeling like the room is spinning
1 (2) 3 (6.1)
Sweating
9 (18.4) 5 (10.2)
Increased body temperature
5 (10.2) 2 (4.1)
Tremor
- 2 (4.1)
Disorientation
2 (4.1) 1 (2)
Yawning
1 (2) 4 (8.2)
Weight gain
7 (14.3) 14 (28.6)
Cell values are frequency (percentage)

28. WEIGHT STATUS
61.3
65.2 66.3
40
45
50
55
60
65
70
75
80
Baseline 14-Day 42-Day
Figure 3: Mean weight (kg) at different time points

29. SUMMARY
▪Mirtazapine was effective in reducing insomnia and depressive symptoms in MDD.
▪On Day 14 at mean dose 22.6 mg/day, 22.4% showed full remission of insomnia
and 14.2% showed full remission of MDD.
▪On Day 42 at mean dose 20.3 mg/day, 67.3% showed full remission of insomnia
and 40.8% showed full remission of MDD.

30. SUMMARY
▪Dry mouth, drowsiness, blurring of vision, headache, increased appetite, sweating,
increased body temperature, weight gain were the most common (>10%) adverse
effects reported by the trial patients.
▪Patients weight gain mean difference was 2.1 kg in the first 14 day period and 4.1
kg over 42 day period.

33. SPECIAL THANKS