Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression

Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression: Role of Inflammation and Kynurenine Pathway Biomarkers

This project will attempt to enhance and augment the antidepressant efficacy of a commonly used antidepressant in poorly responding bipolar depressed patients.

Study Overview

• Status: Completed
• Conditions: Bipolar Depression
• Intervention / Treatment: Drug: Escitalopram; Drug: Celecoxib; Drug: Placebo

Detailed Description

This is a placebo-controlled study of patients with bipolar I disorder (BPD) utilizing a well-known antidepressant, escitalopram (ESC), in combination with the anti-inflammatory agent, celecoxib (CBX). The investigators hypothesize that combination treatment will lead to a qualitatively and quantitatively augmented response and will result in greater numbers of remitters compared to ESC monotherapy.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 21 - 65 years old at time of screening visit. Both genders and any race will be accepted.
• Diagnosis of BPD I or II without significant co-morbid secondary medical or psychiatric diagnoses; no substance abuse or dependence during preceding 12 months
• A minimum score of 18 on the first 17 items of the 21-item Hamilton Depression Scale
• Willingness to washout for a reasonable time (depending on the substance) from: Vitamin E and fish oils (>600 IU/day), non-aspirin NSAIDs or aspirin (>81 mg/day, H2 receptor antagonists, Ginko biloba, caffeine on morning of blood drawing, and to institute lights-out at 23:00 hours on the nights before blood drawings

Exclusion Criteria:

• Any abnormal findings on the physical exam, ECG, blood/urine or minor infections
• Any pre-existing physical pain condition, including fibromyalgia
• History of peptic ulcer complicated by perforation, hemorrhage, or obstruction; symptoms of peptic ulcer within 4 weeks of enrollment date
• Any substance abuse or dependence during the preceding 12 months
• Clinically significant hypertension, anemia, liver disease, kidney disease, arthritis, diabetes, recurrent migraines, epilepsy, stroke, gum disease, autoimmune disease
• Current use of lithium
• Current use of a stimulant
• Certain steroids including use of hormonal birth control and any systemic or topical corticosteroids (hormone replacement therapy will be allowed)
• Unwillingness to refrain from H2 receptor antagonists, non-aspirin NSAIDs, or aspirin (more than 1 mg/day).
• Use of any anticoagulant agents
• Use of nicotine-containing substances. Subjects who quit smoking more than 3 months prior to assessment may be considered for the study
• Known sensitivity or allergy to the study medications or a need to receive agents that are contra-indicated in combination with CBX or ESC
• Unwillingness to fast and abstain from caffeine on mornings of blood drawings
• A sleep disorder other than insomnia or hypersomnia as a distinct symptom of major depressive disorder (MDD)
• Inability to commit to the follow-up visits between 8 and 11 am

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention cohort; Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily.	Drug: Escitalopram; Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI); Other Names: Lexapro; Drug: Celecoxib; Celecoxib is a nonsteroidal anti-inflammatory drug; Other Names: Celebrex
Placebo Comparator: Control cohort; Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily.	Drug: Escitalopram; Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI); Other Names: Lexapro; Drug: Placebo; Placebo is a manufactured capsule with no active ingredient; Other Names: Inactive drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to Treatment	Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, response to treatment is defined as a reduction in the HDRS-17 score of at least 50% after 8 weeks of treatment.	8 weeks
Disease Remission	Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, diisease remission is defined as an HDRS-17 score less than 8 points after 8 weeks of treatment.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of combined ESC/CBX therapy	Determine whether combined pharmacotherapy of ESC + CBX poses safety or tolerability issues, particularly in terms of gastrointestinal bleeding or cardiovascular health over a 8-week course of treatment.	8 weeks

Collaborators and Investigators

• Sponsor: Loyola University
• Collaborators: Stanley Medical Research Institute
• Investigators: Principal Investigator: Angelo Halaris, MD, PhD, Loyola Univeristy Medical Center

Publications and helpful links

General Publications

• Murata S, Murphy M, Hoppensteadt D, Fareed J, Welborn A, Halaris A. Effects of adjunctive inflammatory modulation on IL-1beta in treatment resistant bipolar depression. Brain Behav Immun. 2020 Jul;87:369-376. doi: 10.1016/j.bbi.2020.01.004. Epub 2020 Jan 7.
• Halaris A, Cantos A, Johnson K, Hakimi M, Sinacore J. Modulation of the inflammatory response benefits treatment-resistant bipolar depression: A randomized clinical trial. J Affect Disord. 2020 Jan 15;261:145-152. doi: 10.1016/j.jad.2019.10.021. Epub 2019 Oct 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2011
• Primary Completion (Actual): December 28, 2017
• Study Completion (Actual): January 24, 2018

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (Estimated): November 24, 2011

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Celecoxib; Bipolar depression; Escitalopram
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Cyclooxygenase 2 Inhibitors; Selective Serotonin Reuptake Inhibitors; Celecoxib; Escitalopram
• Other Study ID Numbers: 203368

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.: No