Potential Novel Treatments for Bipolar Depression: Ketamine, Fatty Acids, Anti-inflammatory Agents, and Probiotics

Background: Treatments for depression in bipolar disorder (BD) are far less well developed than for unipolar major depressive disorder. Several innovative and experimental approaches have been emerging recently, including use of the dissociative anesthetic ketamine and other antagonists of central NMDA glutamate receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and possibly probiotic methods. Method: We reviewed relevant reports from the past decade. Findings: Ketamine, a phencyclidine-like NMDA-glutamate receptor antagonist, has emerged as a highly innovative, experimental treatment for treatment-resistant unipolar major depression, possibly in bipolar depression, and with brief antisuicidal effects. Its limitations include poor bioavailability, rapid but short-lived effects, and little information about long-term benefits and safety of repeated administration. Polyunsaturated fatty acids critical for the structure and functioning of neuronal and other cell membranes have some evidence of benefit as experimental treatments for depression including in BD. There also is evidence of altered expression of peptides associated with inflammation in mood disorder patients, encouraging experimental treatment with anti-inflammatory agents; of these, the COX-II inhibitor celecoxib has shown some evidence of benefit. The concept of altering intestinal flora with probiotic treatments to treat mood disorders remains speculative. Conclusion: Ketamine represents an innovative, rapidly acting, experimental treatment for bipolar depression with practical limitations. Unsaturated fatty acids and anti-inflammatory agents have inconsistent support; probiotic treatments lack evidence. These innovative approaches require much more clinical investigation.