Repeated Administrations of Ketamine in Treatment-Resistant Major Depression: Rapid Antidepressant Effects and Durability of Response
James W. Murrough, MD; Andrew M. Perez, MD; Sarah Pillemer, BA; Jessica Stern, BA; Kyle Lapidus, MD, PhD; Laili Soleimani, MD, MsC; Diogo K. Alves, BS; Dennis Charney, MD; and Dan V. Iosifescu, MD, MSc
From the Mood and Anxiety Disorders Program, Department of Psychiatry (Drs Alves, Charney, Iosifescu, Lapidus, Murrough, Pillemer, Soleimani, and Stern); the Department of Anesthesiology (Dr Perez); and the Office of the Dean (Dr Charney), Mount Sinai School of Medicine, New York, New York.
This poster presentation was partially supported by grant UL1RR029887. Dr Murrough is supported by a Career Award (K23MH094707) from NIMH.
Background: Multiple research reports have found that ketamine is associated with rapid antidepressant effects, even in individuals suffering from treatment-resistant depression (TRD). However, most studies have tested single-dose ketamine administration and measured treatment effects over hours or up to a week. There is limited understanding of the safety and efficacy of ketamine beyond a single administration. In the current study we examined the short and longer-term response to repeated administrations of ketamine over two weeks in TRD.
Methods: Participants with TRD (n=23) underwent a washout of antidepressant medication prior to starting a series of six intravenous (IV) infusions of low-dose ketamine (0.5 mg/kg) as monotherapy (administered three times weekly for two weeks). Participants were monitored afterwards for up to 3 months or until relapse.
Results: The overall mean change in Montgomery–Asberg Depression Rating Scale (MADRS) score from baseline to treatment endpoint (post infusion no. 6) was 22.8 (mean baseline MADRS score: 32.1±6.0; endpoint MADRS score: 9.3±11.3). 16/23 participants (70%) met response criteria (defined as a ≥ 50% reduction in MADRS score compared to baseline) at endpoint; responder status at endpoint was strongly predicted by response following the first ketamine administration. During the follow up phase, median time-to-relapse was 20 days (range: 4 days to > 3 months).
Conclusions: Although limited by small sample size and open treatment design, these data suggest that a series of six IV ketamine infusions may be safe and efficacious in patients with TRD and can produce a durable response in a subgroup of patients.
To understand limitations in the current treatment of major depression
To understand the experimental evidence for ketamine as a novel antidepressant
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Murrough JW, Perez AM, Mathew SJ, et al. A case of sustained remission following an acute course of ketamine in treatment-resistant depression. J Clin Psychiatry. 2011;72(3):414–415. PubMed