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