Minocycline and Celecoxib as Adjunctive Treatments of Bipolar Depression

Study Overview
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Brief Summary
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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.

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

Conditions
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Depression, Bipolar Disorder, Bipolar Depression, Mood Disorders

Intervention / Treatment
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* Drug: Minocycline
* Drug: Celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline with TAU<br> | Drug: Minocycline<br> <br> |
| Experimental: Celecoxib with TAU<br> | Drug: Celecoxib<br> <br> |
| Experimental: Minocycline and celecoxib with TAU<br> | Drug: Minocycline<br> <br> Drug: Celecoxib<br> <br> |
| Active Comparator: Placebo with TAU<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Scale scores |  | 12 weeks |