Minocycline and Celecoxib as Adjunctive Treatments of Bipolar Depression

Minocycline and Celecoxib as Adjunctive Treatments of Bipolar Depression: A Factorial Design Randomised Controlled Trial

Bipolar disorder is a leading cause of disability worldwide. A high proportion of patients with bipolar disorder experience persistent depressive symptoms that do not respond to standard drug treatments. Recent evidence has suggested that anti-inflammatory treatment may reduce depressive symptoms. Minocycline is a tetracycline antibiotic with good central nervous system (CNS) penetration that has been suggested to be effective as an adjunct drug in improving depressive symptoms. Celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, has also shown promising results in the treatment of depressive symptoms. In this factorial design, double blind, randomised controlled trial the investigators will determine the efficacy of minocycline and/or celecoxib as an adjunct to treatment as usual (TAU) in patients experiencing a depressive phase of bipolar I or II disorder. The investigators hypothesise that augmentation with minocycline and/or celecoxib will lead to an improvement in depressive symptoms in participants in comparison with placebo.

Study Overview

• Status: Completed
• Conditions: Depression; Mood Disorders; Bipolar Disorder; Bipolar Depression
• Intervention / Treatment: Drug: Placebo; Drug: Celecoxib; Drug: Minocycline

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 69000
      • Dow University of Health Sciences
    • Karachi, Sindh, Pakistan, 72000
      • Institute of Behavioural Sciences
    • Karachi, Sindh, Pakistan, 72000
      • Karwan-e-Hayat
    • Karachi, Sindh, Pakistan
      • Abbasi Shaheed Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18-65 years;
• Diagnostic and Statistical Manual-5 (DSM 5) diagnosis of bipolar I or II disorder and current major depressive disorder;
• Experiencing current depressive symptoms for at least 4 weeks (HAMD-17 score ≥18);
• Competent and willing to give informed consent;
• Taking the current medication for a minimum of 4 week prior to baseline;
• Able to take oral medication;
• If female, willing to use adequate contraceptive precautions and to have monthly pregnancy tests.

Exclusion Criteria:

• Relevant medical illness (HIV, renal, hepatic, cardiac, serious dermatological disorders such as exfoliative dermatitis, systemic lupus erythematosis);
• Prior history of intolerance to any of the tetracyclines or NSAIDs;
• Concomitant penicillin therapy;
• Concomitant anticoagulant therapy;
• Presence of a seizure disorder;
• Currently taking other antibiotics, other NSAIDs, acetazolamide, or methotrexate;
• Any change of psychotropic medications within the previous 4 weeks;
• Diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last 3 months according to DSM-5 criteria;
• Pregnant or breast-feeding;
• Presence of primary psychotic disorder;
• Serious risk of suicide;
• Current three or more manic/hypomanic symptoms.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minocycline with TAU	Drug: Minocycline
Experimental: Celecoxib with TAU	Drug: Celecoxib
Experimental: Minocycline and celecoxib with TAU	Drug: Celecoxib; Drug: Minocycline
Active Comparator: Placebo with TAU	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hamilton Depression Scale scores	12 weeks

Collaborators and Investigators

• Sponsor: Pakistan Institute of Living and Learning
• Collaborators: Stanley Medical Research Institute; University of Manchester; Dow University of Health Sciences; Abbasi Shaheed Hospital; Rawalpindi Medical College, Pakistan

Publications and helpful links

General Publications

• Husain MI, Chaudhry IB, Khoso AB, Husain MO, Hodsoll J, Ansari MA, Naqvi HA, Minhas FA, Carvalho AF, Meyer JH, Deakin B, Mulsant BH, Husain N, Young AH. Minocycline and celecoxib as adjunctive treatments for bipolar depression: a multicentre, factorial design randomised controlled trial. Lancet Psychiatry. 2020 Jun;7(6):515-527. doi: 10.1016/S2215-0366(20)30138-3. Epub 2020 May 20.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: March 4, 2016
• First Submitted That Met QC Criteria: March 8, 2016
• First Posted (Estimate): March 9, 2016

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Depression; Depressive Disorder; Disease; Bipolar Disorder; Mood Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; 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; Anti-Bacterial Agents; Cyclooxygenase 2 Inhibitors; Celecoxib; Minocycline
• Other Study ID Numbers: MIN-BPD