Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York.
Biological psychiatry (Impact Factor: 10.26). 11/2009; 67(2):139-45. DOI: 10.1016/j.biopsych.2009.08.038
Source: PubMed


A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose.
On day 1, patients received a 40-min IV infusion of ketamine (.5 mg/kg) in an inpatient setting with continuous vital-sign monitoring. Psychotomimetic effects and adverse events were recorded repeatedly. The primary efficacy measure was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) score. If patients showed a > or =50% reduction in MADRS scores on day 2, they received five additional infusions on an outpatient basis (days 3, 5, 8, 10, and 12). Follow-up visits were conducted twice-weekly for > or =4 weeks or until relapse.
Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild. The response criterion was met by nine patients after the first infusion as well as after the sixth infusion. The mean (SD) reduction in MADRS scores after the sixth infusion was 85% (12%). Postketamine, eight of nine patients relapsed, on average, 19 days after the sixth infusion (range 6 days-45 days). One patient remained antidepressant-free with minimal depressive symptoms for >3 months.
These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.

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    • "In addition, this was a single-site study, which allowed us to have the same two raters do all the assessments, but the sample size was and the generalizability of the results may be somewhat reduced. Third, similar to all previous studies (Berman et al. 2000; aan het Rot et al. 2010; Katalinic et al. 2013) except for one that used midazolam (Murrough et al. 2013a), saline was used as the inactive placebo. The transient mania-like side-effects in the ketamine group may have compromised the blinding. "
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    • "Ketamine is a schedule III controlled substance in the United States and a schedule I narcotic in Canada. Some of the patients in the experimental trials exhibited adverse effects including perceptual disturbances and transient dissociative symptoms (Zarate et al., 2006; Aan Het Rot et al., 2010). Therefore, it is incumbent upon basic research to determine the mechanism by which ketamine elicits antidepressant actions so that safer drugs can be developed. "
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