Ketamine: Clinical studies in treatment-resistant depressive disorders

Abstract

Since the first report of a robust antidepressant effect of a sub-anesthetic dose of ketamine in 2000, studies have repeatedly confirmed its therapeutic benefits in major depressive disorder (MDD) as well as in depressive episodes in patients with bipolar disorder (BD). Two features of the antidepressant response to ketamine make it striking: first, it can manifest itself within minutes or hours after the transient and generally mild dissociation has disappeared and, second, it has mostly been shown to take place in treatment-resistant patients. The response rate-which is an improvement of 50 % or more-has generally been around 50 % in placebo-controlled studies. Due to the obvious mild dissociative effects of ketamine, low doses of the benzodiazepine midazolam have been used in an attempt to preserve the blind; under such conditions the antidepressant action of ketamine has been confirmed. The main drawback of ketamine is that its antidepressant effects generally do not last more than one week. Several studies have, however, shown that repeated administration can maintain and prolong the response. Finally, clinical experience using repeated administration of ketamine has thus far revealed no significant adverse events; in addition, no tachyphylaxis to the benefits of ketamine in MDD is apparent.