Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatmentresistant depression. However, most trials using ketamine were limited to single administration and were performed with the racemic mixture of ketamine. The aim of this case series was to investigate the clinical efficacy of multiple intravenous administrations of S-ketamine in the acute treatment of treatment-resistant depression.

In 6 patients suffering from Major Depression (DSM-IV criteria) and being pharmacoresistant to at least 2 antidepressants, intravenous Ketamine treatment was started with a 40 minute administration of 0.25 mg S-ketamine/kg body weight i.v. The treatment was performed over 3 weeks using 2 infusions per week. Patients were kept on their current pharmacotherapy regimen (including antidepressants). The patients were rated using the 21-item version of the Hamilton rating scale for depression (HAMD-21) before and 120 minutes after each ketamine infusion.

In 5 of 6 patients a strong improvement of depressive symptoms occurred already after the first ketamine infusion. The response could be stabilized by the following infusions. In 2 patients dissociative symptoms could be seen.

Multiple administrations of ketamine appear to be well tolerated, although negative effects on cognition have been described after longer use. The occurrence of dissociative symptoms in two patients in our study must be viewed as an unpleasant side effect. In the literature there is some evidence, that S-ketamine has better tolerability than racemic ketamine but similar antidepressant effects.