Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. World J Biol Psychiatry. 2007 Jul 10;:1-4 Liebrenz M, Stohler R, Borgeat A. Research Group on Substance Use Disorders, Psychiatric University Hospital, Zurich, Switzerland. Background: The intravenous administration of ketamine, an N-methyl-d-aspartate receptor antagonist, results in a great improvement of depression symptoms, but it is not clear for how long. This single-case trial was conducted to explore the duration of improvement and the effects of a second administration on the clinical outcome. Methods: In an open label trial, a 55-year-old male patient with treatment-resistant major depression and a co-occurring alcohol and benzodiazepine dependence received two intravenous infusions of 0.5 mg/kg ketamine over the course of 6 weeks. Depression severity was assessed by means of a weekly clinical interview, the 21-item Hamilton Depression Rating Scale (HDRS), and the 21-item Beck Depression Inventory (BDI). Results: The first ketamine infusion lead to a pronounced improvement of symptoms, peaking on the second day post infusion (HDRS -56.6%, BDI -65.4%). Positive effects started fading by day 7, reaching baseline by day 35. The second infusion was less efficacious: HDRS and BDI were reduced by 43 and 35%, respectively, and returned to baseline by day 7. Conclusion: In this patient with a co-occurring substance use disorder, repeated administrations of ketamine produced positive results. Since the second application has been less efficacious, doses and schedule of administrations need to be further investigated.