Single-dose ketamine followed by daily D-cycloserine in treatment-resistant bipolar depression.

Bipolar depression is a leading cause of disability in the United States. Recently, N-methyl-D-asparate glutamate-receptor (NMDAR) antagonists, such as ketamine, have been shown to induce remission in bipolar depression. Nevertheless, ketamine use is limited by transient effects and psychogenic potential during repeated administration. D-Cycloserine is a US Food and Drug Administration (FDA)-approved antituberculosis drug that acts as an NMDAR antagonist when used at high doses (>750 mg). D-Cycloserine targets the glycine coreceptor of the NMDAR and may have improved safety relative to ketamine (analogous to use of benzodiazepines vs barbiturates at γ-aminobutyric acid-A receptors). Antidepressant effects of D-cycloserine were first noted in the 1950s. However, double-blind, placebo-controlled studies at high doses were not conducted until recently. A large, betweengroup, large effect-size (d = 0.91, P=.005) difference was seen in unipolar depression, corresponding to a mean 48% reduction in symptoms. We report the first study of acute ketamine followed by daily D-cycloserine in bipolar depression (ClinicalTrials.gov identifier NCT01833897). (PsycINFO Database Record (c) 2016 APA, all rights reserved)