Anti-inflammatory treatment of bipolar depression: promise and disappointment

The management of depression remains the principal unmet need in bipolar disorder. 1 Yatham LN Kennedy SH Parikh SV et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018; 20: 97-170 Crossref PubMed Scopus (729) Google Scholar Consequently, the presence of inflammation in a considerable subset of people with the disorder opens the door to potentially exciting therapies, 2 Vieta E Disruptive treatments in psychiatry. Rev Psiquiatr Salud Ment. 2020; 13: 1-4 Crossref PubMed Scopus (4) Google Scholar with celecoxib and minocycline among the most promising options. This promise is predicated on encouraging preclinical and epidemiological data as well as positive studies in related disorders, especially major depression. 3 Dean OM Kanchanatawan B Ashton M et al. Adjunctive minocycline treatment for major depressive disorder: a proof of concept trial. Aust N Z J Psychiatry. 2017; 51: 829-840 Crossref PubMed Scopus (66) Google Scholar , 4 Sethi R Gómez-Coronado N Walker AJ et al. Neurobiology and therapeutic potential of cyclooxygenase-2 (COX-2) inhibitors for inflammation in neuropsychiatric disorders. Front Psychiatry. 2019; 10: 605 Crossref PubMed Scopus (35) Google Scholar , 5 Dean OM Data-Franco J Giorlando F Berk M Minocycline. CNS drugs. 2012; 26: 391-401 Crossref PubMed Scopus (107) Google Scholar The negative results of a large trial reported in The Lancet Psychiatry by Muhammad Husain and colleagues, 6 Husain MI Chaudhry IB Khoso AB et al. Minocycline and celecoxib as adjunctive treatments for bipolar depression: a multicentre, factorial design randomised controlled trial. Lancet Psychiatry. 2020; 7: 515-527 Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar which was capable of making these two drugs viable treatment options for bipolar depression, are thus very disheartening. Minocycline and celecoxib as adjunctive treatments for bipolar depression: a multicentre, factorial design randomised controlled trialWe found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression. Full-Text PDF Assessing adjunctive treatments for bipolar depressionWe thank Michael Berk and colleagues for sharing their thoughts on our study.1 Although we have no fundamental disagreement with much of their comment, we would like to respond to the suggestion that our study could be conceptualised as a "failed" trial, including that it might not have detected the efficacy of a drug with established benefit, that the placebo effect was too great, and that in any case, expecting a single approach to therapy to be effective in a patently heterogeneous condition was "ambitious". Full-Text PDF