Ketamine in Bipolar Disorder: A Review

Introduction

Bipolar disorder (BD) is a recurrent, highly morbid psychiatric illness affecting over 1% of the population and carrying the highest lifetime suicide risk among psychiatric disorders. Patients with BD spend a large proportion of their lives depressed, and bipolar depression shows higher treatment-failure rates than major depressive disorder; longer depressive episodes are associated with neuroprogression, structural brain changes, and cognitive deficits. Given these unmet needs, novel treatments for refractory bipolar depression are required. Ketamine has demonstrated rapid antidepressant and antisuicidal effects in treatment‑resistant populations, but most research has focused on unipolar depression and bipolar patients are underrepresented in clinical trials. Wilkowska and colleagues set out to review the existing clinical, molecular, and preclinical evidence regarding ketamine’s potential benefits and mechanisms in BD. The review aims to summarise single- and multiple‑dose clinical data, discuss risks such as affective switch, and examine molecular pathways (for example glutamatergic signalling, BDNF, synaptogenesis, epigenetics, inflammation, and the microbiome) that could underlie ketamine’s effects in bipolar illness, with a view to informing future trials and clinical practice.