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

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.

Study Overview

• Status: Withdrawn
• Conditions: Postpartum Depression
• Intervention / Treatment: Drug: Placebo; Drug: Trazodone

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • Parkwood Institute Mental Health Care Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Healthy outpatients with a history of Major depressive disorder who are currently not on any psychotropic medications and who:

1. are 18- 45 years old,
2. are pregnant with gestation of 28-34 weeks,
3. have been in full remission of depression for > 2 months (as per Diagnostic and Statistical Manual-5),
4. are able to communicate in English,
5. are capable of providing informed consent,
6. are planning to deliver at Victoria Hospital in London Ontario, and
7. live in London and the surrounding area, will be enrolled.

Exclusion Criteria:

1. current psychiatric disorder other than generalized anxiety,
2. use of psychotropic medication over the previous 2 months,
3. history of bipolar disorder or psychosis,
4. high risk for suicide (actively suicidal or a score of ≥ 3 on item #3 on the Hamilton Depression Rating Scale-17 item [HDRS]),
5. currently receiving psychotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trazodone; Trazodone once daily for 24 weeks.	Drug: Trazodone; Trazodone capsule once daily
Placebo Comparator: Placebo; Placebo once daily for 24 weeks	Drug: Placebo; Placebo capsule once daily

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

Collaborators and Investigators

• Sponsor: Verinder Sharma
• Investigators: Principal Investigator: Verinder Sharma, MB, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Study record dates

Study Major Dates

• Study Start (Estimated): April 17, 2025
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: December 30, 2021
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Prevention; Postpartum depression; Trazodone
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Behavioral Symptoms; Mood Disorders; Puerperal Disorders; Depression; Depressive Disorder; Depression, Postpartum; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Membrane Transport Modulators; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Trazodone
• Other Study ID Numbers: 120394

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No