compared with ketamine alone, and second, the time Doxorubicin course of antidepressant response to a single intravenous dose of the NMDA antagonist ketamine. Following a 2 week drug free period, 42 subjects with TRD currently experiencing a major depressive episode without psychotic features received a single open label infusion of 0.5 mg/kg of ketamine hydrochloride over 40 min via a Baxter infusion pump by an anesthesiologist in the peri anesthesia care unit. Ketamine dose was based on previous studies of patients with mood disorders. Four to six hours post infusion, patients were randomized in a doubleblind manner to receive either riluzole or placebo for 4 weeks. All study investigators, staff, and patients were blind to riluzole or placebo assignment.
For patients in the ketamine riluzole group, the dose of riluzole was initiated and maintained at 100 mg/day. During weekly evaluations, this dose Pemetrexed Alimta could be flexibly increased in increments of 50 mg to a maximum of 200 mg/day. Dose escalations continued on a weekly basis until the appearance of treatment limiting side effects or completion of the study. Dose reductions were permitted by one capsule in case of side effects. Subjects who were unable to tolerate the lowest dose of riluzole allowable were discontinued from the study. Treatment compliance was monitored by capsule counts and by the nurses who administered the study medication. No additional medications that primarily affect the central nervous system were allowed during the study. Patients were hospitalized at the CRC of the NIMH NIH for the duration of the study.
Vital signs, digital oximetry, and ECG were monitored during the ketamine infusion as well as for one hour post infusion. Complete blood counts, electrolyte panels, and liver function tests were obtained at baseline and at weeks 2 and 4, or at study exit. ECGs were obtained at baseline and at the end of the study. Main Outcome Measures Lenalidomide TNF-alpha Receptor inhibitor Subjects were rated 60 min prior to ketamine infusion, at 40, 80, 120, and 230 min post infusion, and then daily for the next 28 days following the infusion. Rating scales included the MADRS, which was the primary outcome measure. Secondary measures were the 17 item Hamilton Rating Scale for Depression, the self administered Beck Depression Inventory, the visual analogue scale for depression, the Hamilton Anxiety Rating Scale, the Brief Psychiatric Rating Scale positive symptoms, the Clinician Administered Dissociative States Scale, the Young Mania Rating Scale, and the Scale for Suicide Ideation.
The HAM A was obtained at baseline, 230 min, and on days 1, 3, 7, 14, 21, and 28. Patient ratings were performed by research nurses, a physician, and a psychologist who trained together to establish reliability. High inter rater reliability was obtained for the MADRS ¼ 0.94, buy Ramelteon HAM D, and YMRS. Throughout the study, the same rater conducted most ratings for an individual patient. Ketamine and Norketamine Plasma Levels Ketamine and norketamine plasma levels were obtained at introspection 40 and 80 min post infusion. Statistical Analyses Linear mixed models with restricted maximum likelihood estimation were used to examine the change in clinical ratings over the course of the study. Study day was a withinsubjects factor and treatment group was a between subjects factor.