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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Available from: Marije aan het Rot, Sep 30, 2015
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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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    • "In Case 3, treatment-resistant depression with suicidality showed sudden decrease in depression as assessed on MADRS, CGI-S scores from 34, 7 to 14 and CGI-I score of 2, indicating marked therapeutic effects and side effects do not require any intervention; they were mild and remitted within about 2 hours. Aan het Rot et al., [10] administered a single ketamine (0.5 mg/kg) infusion to 10 patients with treatment-refractory depression; a day later, MADRS scores in nine patients showed >50% attenuation. These nine patients received five more ketamine infusions across the next 10 days. "
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    • "Compte tenu de ces résultats encourageants à court terme mais à l'efficacité limitée dans le temps, Rot et al. [31] se sont intéressés en 2010 à la tolérance, la sûreté et l'efficacité d'un traitement répété par kétamine en intraveineux (0,5 mg/kg). Dix patients souffrant d'une dépression résistante ayant répondu à une première injection IV de kétamine à dose infra-anesthésique ont reçu 5 injections supplémentaires sur 12 jours, et les symptômes dépressifs ont été évalués régulièrement pendant 1 mois. "
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