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Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

  • James W. Murrough
    Correspondence
    Address correspondence to James W. Murrough, M.D., Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1230, New York, NY 10029
    Affiliations
    Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York

    Department of Neuroscience, Mount Sinai School of Medicine, New York, New York
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  • Andrew M. Perez
    Affiliations
    Department of Anesthesiology, Mount Sinai School of Medicine, New York, New York
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  • Sarah Pillemer
    Affiliations
    Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
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  • Jessica Stern
    Affiliations
    Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
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  • Michael K. Parides
    Affiliations
    Center for Biostatistics, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York
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  • Marije aan het Rot
    Affiliations
    Experimental Psychopathology Program, Department of Psychology, University of Groningen, Groningen, the Netherlands

    School of Behavioral and Cognitive Neuroscience, University of Groningen, Groningen, the Netherlands
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  • Katherine A. Collins
    Affiliations
    Department of Neuroscience, Mount Sinai School of Medicine, New York, New York
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  • Sanjay J. Mathew
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas

    Michael E. Debakey VA Medical Center, Houston, Texas
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  • Dennis S. Charney
    Affiliations
    Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York

    Department of Neuroscience, Mount Sinai School of Medicine, New York, New York

    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York

    Office of the Dean, Mount Sinai School of Medicine, New York, New York
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  • Dan V. Iosifescu
    Affiliations
    Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York

    Department of Neuroscience, Mount Sinai School of Medicine, New York, New York
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      Background

      Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original.

      Methods

      Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion.

      Results

      The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery–Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days.

      Conclusions

      Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.

      Key Words

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