Prevention of Postpartum Depression: A Pilot Placebo-controlled Trial of Trazodone

Study Overview
=================
Brief Summary
-----------------
Postpartum depression is a serious illness that affects approximately 17% of women who have recently given birth. Untreated depression appears to have negative effects for both the mother and her baby. Postpartum depression is quite common among women with a history of depression. Sleeplessness is a common concern during pregnancy and after delivery, and it can also trigger depression in women with a history of depression. Antidepressants are the most commonly recommended drugs for prevention of postpartum depression; however, there is limited research to understand the effectiveness of the medications in preventing postpartum depression. Trazodone is a weak antidepressant, but it is commonly prescribed for sleeplessness due to physical or psychiatric disorders. We are planning a study to find out whether trazodone in a low dose is more effective than a sugar pill in preventing postpartum depression among women with histories of depression. We expect the results of our study will make it easier for healthcare providers to select the right medication for women who are at risk of developing depression after delivery and thus improve the mental health of mothers and well-being of their babies.

Official Title
-----------------
Prevention of Postpartum Depression: A Pilot Placebo-controlled Trial of Trazodone

Conditions
-----------------
Postpartum Depression

Intervention / Treatment
-----------------
* Drug: Trazodone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy outpatients with a history of Major depressive disorder who are currently not on any psychotropic medications and who: are 18- 45 years old, are pregnant with gestation of 28-34 weeks, have been in full remission of depression for > 2 months (as per Diagnostic and Statistical Manual-5), are able to communicate in English, are capable of providing informed consent, are planning to deliver at Victoria Hospital in London Ontario, and live in London and the surrounding area, will be enrolled. Exclusion Criteria: current psychiatric disorder other than generalized anxiety, use of psychotropic medication over the previous 2 months, history of bipolar disorder or psychosis, high risk for suicide (actively suicidal or a score of ≥ 3 on item #3 on the Hamilton Depression Rating Scale-17 item [HDRS]), currently receiving psychotherapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trazodone<br>Trazodone once daily for 24 weeks. | Drug: Trazodone<br>* Trazodone capsule once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily for 24 weeks | Drug: Placebo<br>* Placebo capsule once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Major depressive episode | Participants having a score of >7 on the Hamilton Depression Rating Scale (Max 52) will be assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders- 5 (SCID-5) to establish recurrence of an major depressive episode. A higher score indicates recurrence of an MDE | 27 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to occurrence of Major Depressive Episode (MDE) | The time from childbirth until they develop MDE | 27 weeks | 
| Hamilton Depression Rating Scale | The change in Hamilton Depression Rating Scale and Scale from baseline to 24 weeks to measure change in depressive symptoms. The score ranges from 0-53 where a higher score is a worse outcome. | 24 weeks | 
| Edinburgh Postnatal Depression | The change in Edinburgh Postnatal Depression Scale from baseline to 24 weeks to measure the change in depressive symptoms. The scores range from 0 to 30 with 30 indicating more depression symptoms. | 24 weeks | 
| Blood pressure | The systolic and diastolic blood pressure will be measured in mmHG. | 27 weeks | 
| Pulse | Pulse will be measured in Beats per minute | 27 weeks | 
| Body weight | Body weight will be measured in kilograms | 27 weeks | 
| Side effects | Side effects of Trazodone will be measured by the Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale | 27 weeks | 
| Maternal Functioning | Maternal Functioning will be measured by Barkin Index of Maternal Functioning. The sum of the scores is calculated, ranging from 0 to 120. Where a score of 120 means perfect functioning. The different between the scores scores will be looked at and a more positive score (8 week score is greater than baseline score) is a better outcome. | 27 weeks | 
| Development of mania symptoms | Mania symptoms will be measured by the Young Mania Rating Scale. here are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others. The score ranges from 0 to 60 where 60 indicates a worse outcome. | 27 weeks | 
| Pill count | Adherence to intervention | 27 weeks | 
| Retention rate | The following criteria will be used to determine the success of the study: enrollment of 1 participant every 2 weeks, and recruitment of at least 60% of all patients considered eligible to participate in the study | 27 weeks | 
| Complete blood count (CBC) | The CBC is a blood test to check the overall health of the participant | 27 weeks | 
| Thyroid Stimulating Hormone test | a blood test that measures Thyroid Stimulating Hormone measured in the units mIU/L | 27 weeks | 
| Electrocardiogram QT Interval | test that checks the QT interval of the heart. This will let us know if the participants have heart abnormalities or if the medication has made changes to the heart of the participant. | 27 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Postpartum depression, Trazodone, Prevention