Ketamine Produced Quick Antidepressant Effect in Test

Abstract

SAN FRANCISCO – The anesthetic ketamine produced a significant and rapid antidepressant effect in a randomized, blinded, proof-of-concept study in 73 patients with treatment-resistant depression. Within 24 hours, 64% of patients given an intravenous infusion of ketamine showed a response, compared with 28% of patients who showed a response in a control group given the anesthetic midazolam, which mimics the anesthetic effects of ketamine but without any antidepressant effects, Dr. James W. Murrough and his associates reported. Patients were assessed for depression before the infusion, 24 hours later, and again at days 2, 3, and 7 using the Montgomery-Asberg Depression Scale (MADRS). The ketamine group showed sustained improvement in MADRS scores up to a week after the infusion, Dr. Murrough said during a press briefing at the annual meeting of the American Psychiatric Association. Ketamine is not approved to treat depression and it is premature to say that it should be, he noted. Data are needed on the efficacy and safety of taking ketamine over time, among other research questions, said Dr. Murrough of the departments of psychiatry and neuroscience at Mount Sinai School of Medicine, New York. Previous studies had suggested that ketamine may have a rapid antidepressant effect in treatment-resistant depression, but those studies were limited by small sample sizes, single-site cohorts, and other parameters. Editor's NoteKetamine, a dissociative anesthetic (similar to phencyclidine, or PCP) and popular recreational “club drug” (sometimes referred to as “Special K”) shows promise for depression and, in some situations, can be used for pain, particularly neuropathy. It's obviously off-label use, and it is a Schedule III controlled substance. Its traditional medical and veterinary uses are via a parenteral route.However, it can be compounded into oral form and, according to some experts, is even more effective in a transdermal formulation because of degradation when taken orally. It seems to be rapidly effective for depression and can be useful in severe or treatment-resistant cases, where other modalities (such as electroconvulsive therapy and transcranial magnetic stimulation) are not feasible.Most compounding pharmacies can readily obtain and formulate ketamine capsules or transdermal gels or creams. I have had some success in depressed hospice patients using oral ketamine. It is not prohibitively expensive and seems to be a nice addition to our armamentarium for those of us who sometimes think outside the box in the interest of our patients’ comfort and quality of life.—Karl Steinberg, MD, CMD,Editor in Chief Ketamine, a dissociative anesthetic (similar to phencyclidine, or PCP) and popular recreational “club drug” (sometimes referred to as “Special K”) shows promise for depression and, in some situations, can be used for pain, particularly neuropathy. It's obviously off-label use, and it is a Schedule III controlled substance. Its traditional medical and veterinary uses are via a parenteral route. However, it can be compounded into oral form and, according to some experts, is even more effective in a transdermal formulation because of degradation when taken orally. It seems to be rapidly effective for depression and can be useful in severe or treatment-resistant cases, where other modalities (such as electroconvulsive therapy and transcranial magnetic stimulation) are not feasible. Most compounding pharmacies can readily obtain and formulate ketamine capsules or transdermal gels or creams. I have had some success in depressed hospice patients using oral ketamine. It is not prohibitively expensive and seems to be a nice addition to our armamentarium for those of us who sometimes think outside the box in the interest of our patients’ comfort and quality of life. —Karl Steinberg, MD, CMD, Editor in Chief In this study, patients were randomized to receive 0.5 mg/kg of ketamine or 0.045 mg/kg of midazolam over 40 minutes. The patients were supervised and monitored by an anesthesiologist and spent the night on the clinical research unit. The MADRS scores before treatment were approximately 32 in both groups. Within 24 hours, the primary endpoint, MADRS scores were approximately 16 in the ketamine group, a significant improvement, compared with 22 in the midazolam group, a nonsignificant change from baseline. Among secondary endpoints, MADRS scores held steady in both groups on days 2 and 3. By day 7, MADRS scores were approximately 18 in the ketamine group and 24 in the midazolam group, with ketamine's effect no longer being statistically significant. Future studies should look at biomarkers and mechanisms of action when using ketamine to treat depression, its long-term safety and efficacy, and novel therapeutic targets. Dr. Murrough reported research funding from Janssen Pharmaceuticals, Avanir Pharmaceuticals, and Evotec/Roche.