This was a single-center, double-blind, randomized, crossover, placebo-controlled study conducted to assess the efficacy and safety of a single intravenous infusion of the NMDA antagonist ketamine combined with lithium or valproate therapy in the treatment of bipolar I or II depression. As noted previously, subjects were first required to have failed to respond to a prospective open trial of therapeutic levels of either lithium or valproate at the NIMH for a minimum of 4 weeks, regardless of whether they were already taking therapeutic levels of lithium or valproate at admission. During the entirety of the study, patients were required to take either lithium or valproate within the specified range and were not allowed to receive any other psychotropic medications (including benzodiazepines) or to receive structured psychotherapy. Lithium and valproate levels were obtained weekly. Vital signs and oximetry were monitored during the infusion and for 1 hour after. Electrocardiograms, complete blood counts, electrolyte panels, and liver function tests were obtained at baseline and at the end of the study.
Following nonresponse to open treatment with lithium or valproate and a 2-week drug-free period (except for treatment with lithium or valproate), subjects received intravenous infusions of saline solution and 0.5-mg/kg ketamine hydrochloride 2 weeks apart using a randomized, double-blind, crossover design. The ketamine dose was based on previous controlled studies of patients with major depressive disorder.30 (link),33 (link),34 (link)
Patients were randomly assigned to the order in which they received the 2 infusions via a random-numbers chart. Study solutions were supplied in identical 50-mL syringes containing either 0.9% of saline or ketamine with the additional volume of saline to total 50 mL. Ketamine forms a clear solution when dissolved in 0.9% saline. The infusions were administered over 40 minutes via a Baxter infusion pump (Deerfield, Illinois) by an anesthesiologist in the perianesthesia care unit. All staff, including the anesthesiologist, was blind to whether drug or placebo was being administered.
Following nonresponse to open treatment with lithium or valproate and a 2-week drug-free period (except for treatment with lithium or valproate), subjects received intravenous infusions of saline solution and 0.5-mg/kg ketamine hydrochloride 2 weeks apart using a randomized, double-blind, crossover design. The ketamine dose was based on previous controlled studies of patients with major depressive disorder.30 (link),33 (link),34 (link)
Patients were randomly assigned to the order in which they received the 2 infusions via a random-numbers chart. Study solutions were supplied in identical 50-mL syringes containing either 0.9% of saline or ketamine with the additional volume of saline to total 50 mL. Ketamine forms a clear solution when dissolved in 0.9% saline. The infusions were administered over 40 minutes via a Baxter infusion pump (Deerfield, Illinois) by an anesthesiologist in the perianesthesia care unit. All staff, including the anesthesiologist, was blind to whether drug or placebo was being administered.
