Elsevier

Biological Psychiatry

Volume 67, Issue 2, 15 January 2010, Pages 139-145
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2009.08.038Get rights and content

Background

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.

Methods

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-Åsberg Depression Rating Scale (MADRS) score. If patients showed a ≥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 ≥4 weeks or until relapse.

Results

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.

Conclusions

These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.

Section snippets

Participants

Participants were patients with chronic or recurrent MDD, as per the Structured Clinical Interview for DSM-IV-TR (7), who had had an insufficient therapeutic response to ≥2 adequate antidepressant medication trials in the current episode, as per the Antidepressant Treatment History Form (ATHF) (8). All had previously participated in an open-label, single-dose IV ketamine study; had evinced a ≥50% reduction in the severity of their depressive symptoms for at least 24 hours without any

Results

Ten participants received the first IV ketamine infusion. Nine of these participants met response criteria at t+24h (see following text for details) and were eligible for subsequent infusions. One patient missed the fourth infusion.

Discussion

We have presented preliminary data supporting feasibility of repeated-dose IV ketamine in a group of TRD patients who had previously shown a favorable response to a single IV ketamine infusion. Safety, tolerability, and duration of symptom relief during the course of treatment were the criteria established to assess feasibility. Six IV infusions of ketamine administered thrice-weekly over 40 min at a .5 mg/kg dose were well-tolerated. No patient reported greater than mildly bothersome side

References (24)

  • M.B. First et al.

    Structured Clinical Interview for DSM-IV TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P)

    (2001)
  • H.A. Sackeim

    The definition and meaning of treatment-resistant depression

    J Clin Psychiatry

    (2001)
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