Efficacy And Tolerability Of Sub-Anesthetic Ketamine In Postpartum Depression

Postpartum depression is a non-psychotic major or minor depressive episode that occurs during pregnancy or within 12 months of post-partum period. The nature of symptoms is same as depressive episode characterized by depressed mood, anxiety, sleep difficulties, suicidal thoughts, tiredness and diminished interest in pleasurable activities. Severe maternal depression affects children by increasing the risk of emotional and behavioral and physical health problems and cognitive difficulties. Thus early screening and intervention is critical in reducing the negative impact of PND in the mother and child, family and the community.

The purpose of this study is to assess the safety, pharmacokinetics and antidepressant efficacy of sub-anesthetic dose of intravenous ketamine in perinatal depression.

Study Overview

• Status: Terminated
• Conditions: Post Partum Depression
• Intervention / Treatment: Drug: Ketamine 0.5 mg/kg; Drug: Ketamine 0.2 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77054
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female subjects, ages 18-45 years
• Experienced a major depressive episode in the postpartum period beginning within the first 4 weeks following delivery and with moderate or severe symptoms (>12 EPDS or >14 HAM-D).
• No or partial response to adequate doses of SSRI medications to treat PND for longer than 6 weeks.
• PND patients will be requested to maintain the stable dose of antidepressants while enrolled in the study trial.
• Patients that can speak and read the English language, are able to understand the study procedures and sign the informed consent

Exclusion Criteria:

• No current or past psychosis or severe personality disorder.
• No current substance abuse or dependence.
• No serious and imminent suicidal or homicidal risk.
• No recent or history of major and unstable medical problems that affect brain anatomy, neurochemistry, or function.
• Not diagnosed with cardiovascular disorders.
• No increased risk of laryngospasm or active upper respiratory infections.
• Not diagnosed with an intellectual disability or neurodegenerative diseases.
• Mothers that are currently breastfeeding.
• No current pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine 0.5 mg/kg, then Ketamine 0.2 mg/kg; single intravenous infusion of Ketamine (0.5 mg/kg), washout period of seven days, and then single intravenous infusion of Ketamine (0.2 mg/kg)	Drug: Ketamine 0.5 mg/kg; single intravenous infusion of Ketamine (0.5 mg/kg); Other Names: Ketamine Hydrochloride; Drug: Ketamine 0.2 mg/kg; single intravenous infusion of Ketamine (0.2 mg/kg)
Experimental: Ketamine 0.2 mg/kg, then Ketamine 0.5 mg/kg; single intravenous infusion of Ketamine (0.2 mg/kg), washout period of seven days, and then single intravenous infusion of Ketamine (0.5 mg/kg)	Drug: Ketamine 0.5 mg/kg; single intravenous infusion of Ketamine (0.5 mg/kg); Other Names: Ketamine Hydrochloride; Drug: Ketamine 0.2 mg/kg; single intravenous infusion of Ketamine (0.2 mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depressed Mood as Indicated by Hamilton Depression Rating Scale (HAM-D) Score	The Hamilton Depression Rating Scale (HAM-D) score ranges from 0-53. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity of depressive symptoms. The value reported is the score at baseline minus the score 24 hours post-injection.	baseline, 24 hours post-injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment-Emergent Adverse Events		24 hours post-injection
Change in Postnatal Depression as Indicated by Edinburgh Postnatal Depression Scale (EPDS) Scale	The Edinburgh Postnatal Depression Scale (EPDS) score ranges from 0 to 30. Higher scores indicate worse outcome, with a score of 10 or greater indicating depression. The value reported is the score at baseline minus the score at 24 hours post-injection.	baseline, 24 hours post-injection
Change in Anxiety as Indicated by Generalized Anxiety Disorder 7-Item (GAD-7) Scale	The Generalized Anxiety Disorder 7-Item (GAD-7) Scale score ranges from 0 to 21, with higher scores indicating greater anxiety. The value reported is the score at baseline minus the score 24 hours post-injection.	baseline, 24 hours post-injection
Change in Depression as Indicated by Patient Health Questionnaire (PHQ-9)	The Patient Health Questionnaire (PHQ-9) score ranges from 0 to 27, with greater scores indicating more severe depression.	baseline, 24 hours post-injection
Change in Behavioral Suicidal Events (Suicidal Ideation), as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors". The C-SSRS outcomes are categories and have binary responses (yes/no). Suicidal ideation is considered when the patient responds a "yes" answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS. The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation).	baseline, 24 hours post-injection
Change in Behavioral Suicidal Events (Suicidal Behavior), as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	The questions 6-10 of the C-SSRS are related to suicidal behavior, and the outcome is a simple yes/no response. Suicidal behavior occurs if the patient answers a "yes" at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10) on the C-SSRS.	baseline, 24 hours post-injection

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Sudhakar Selvaraj, 713-486-2837, UTHealth Science Center at Houston

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2019
• Primary Completion (Actual): September 9, 2019
• Study Completion (Actual): September 9, 2019

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Pregnancy Complications; Puerperal Disorders; Depression; Depressive Disorder; Depression, Postpartum; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: HSC-MS-18-0416

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes