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.

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.