Effect of Tramadol in Prevention of Postpartum Depression (ETPPD)

The incidence of postpartum depression in Europe and the United States is about 10%, while in China the incidence rate of 15.7-39.8%. Postpartum depression is one of the most common diseases of perinatal distress, but the current research of high-quality prevention and treatment of postpartum depression is still very lack. The study suggests that the risk of postpartum depression in cesarean delivery is significantly higher than that in vaginal delivery. Therefore, postpartum depression in cesarean delivery may require more attention and treatment.Tramadol is a non-opioid central analgesic that relieves common to severe pain, and tramadol has an inhibitory effect on norepinephrine and serotonin systems and has the potential to reduce depression and anxiety. Therefore, for the analgesic demand and antidepressant demand for maternal who undergoing cesarean section, tramadol may be an optimized and effective analgesic for the prevention and treatment of postpartum depression.

Study Overview

• Status: Completed
• Conditions: Caesarean Section
• Intervention / Treatment: Drug: Tramadol; Drug: Hydromorphone; Drug: Ropivacaine (Epidural analgesia)

Detailed Description

This study was designed according to a prospective, randomized, controlled clinical trial. Randomized subjects were randomly assigned to different analgesic drug-treated groups according to the random number induced by SPSS software. All three analgesic treatments were routinely used for clinical analgesia; Anesthesia, surgery, postoperative treatment are in accordance with clinical practice. The investigators conducted a postoperative questionnaire survey and psychological diagnosis for all patients. And blood sample was collected from patients before and 48 hours after the surgery.

• Study Type: Interventional
• Enrollment (Actual): 1230
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Xinqiao Hospital, Third Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 20 years old ≤ age ≤ 40 years old;
• ASA score I-Ⅱ;
• uncomplicated and singleton full-term pregnancy;
• voluntarily to receive cesarean section and postoperative controlled analgesia;
• consent to participate the study.

Exclusion Criteria:

• with history of mental disorders or psychotropic substances use;
• with history of neurological diseases such as epilepsy
• with history of previously known diagnosed depression;
• with suicidal ideation or history of suicide;
• with history of drug，alcohol or opioid abuse;
• with monoamine oxidase (MAO) inhibitor treatment at present or in the past 14 days;
• participating in other clinical studies
• with severe heart disease, brain disease, liver disease and kidney disease;
• be allergic to tramadol or opioids;
• with any contraindication for combined spinal epidural anesthesia;
• incapable of communication or cooperation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group T; All patients receive the patient-controlled intravenous analgesia with Tramadol.	Drug: Tramadol; Patient-controlled intravenous analgesia with Tramadol
Placebo Comparator: Group H; All patients receive the patient-controlled intravenous analgesia with Hydromorphone.	Drug: Hydromorphone; Patient-controlled intravenous analgesia with Hydromorphone
Placebo Comparator: Group E; All patients receive the patient-controlled epidural analgesia with Ropivacaine.	Drug: Ropivacaine (Epidural analgesia); Patient-controlled epidural analgesia with Ropivacaine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of postpartum depression	Diagnosed according to DSM-5 diagnostic criteria for postnatal depression	At 4 weeks after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of postpartum depression	Diagnosed according to DSM-5 diagnostic criteria for postnatal depression	At 3 months after the surgery
EPDS scores	Measured using Edinburgh Postnatal Depression Scale	At 4 weeks and 3 months after the surgery
GAD-7 scores	Measured using Generalized Anxiety Disorder Scale	At 4 weeks and 3 months after the surgery
QoR-15 scores	Measured using Quality of recovery 15	48 hours after the surgery
Pain intensity	Pain VAS at 6, 12, 24 and 48 hours after the surgery	At 6, 12, 24 and 48 hours after the surgery
Norepinephrine and serotonin levels in the blood	Norepinephrine and serotonin concentration in the blood at 48 hours after the surgery	At 48 hours after the surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early walking time	The time for patient to independently activity	During hospitalization, an average of 36 hours
Hospital stays	The time for patient to stay in hospital after the surgery	During hospitalization, an average of 72 hours
Pain intensity	Postoperative pain intensity that evaluated by questionnaire at 3 months after the surgery	At 3 months after the surgery

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing

Publications and helpful links

General Publications

• Wu Z, Zhao P, Peng J, Fang L, Ding J, Yan G, Wang Y, Zhu J, Wang D, Li Y, Chen Z, Zhang Q, Deng Q, Duan G, Zuo Z, Li H. A Patient-Controlled Intravenous Analgesia With Tramadol Ameliorates Postpartum Depression in High-Risk Woman After Cesarean Section: A Randomized Controlled Trial. Front Med (Lausanne). 2021 May 27;8:679159. doi: 10.3389/fmed.2021.679159. eCollection 2021.
• Duan G, Wu Z, Zhao P, Peng J, Chen Z, Zhang Q, Xu R, Li H. Protocol for a randomised, double-blind, placebo-controlled trial to explore the effect of tramadol in the prevention of postpartum depression (ETPPD). BMJ Open. 2018 Oct 21;8(10):e022538. doi: 10.1136/bmjopen-2018-022538.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Actual): June 13, 2019
• Study Completion (Actual): August 13, 2019

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: October 12, 2017
• First Posted (Actual): October 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Pregnancy Complications; Puerperal Disorders; Depressive Disorder; Depression, Postpartum; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Ropivacaine; Tramadol; Hydromorphone
• Other Study ID Numbers: ETPPD Trail

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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