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From Mice to Men: Can Ketamine Enhance Resilience to Stress?

  • Rebecca B. Price
    Correspondence
    Address correspondence to Rebecca B. Price, Ph.D., Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213.
    Affiliations
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Published:February 15, 2016DOI:https://doi.org/10.1016/j.biopsych.2016.02.011
      The rapid antidepressant properties of intravenous ketamine have ignited high hopes from researchers, clinicians, and patients alike. Although bottom-up patient demand has led some clinicians to offer repeated ketamine infusions directly to patients, academic commentators have warned against premature clinical adoption (
      • Schatzberg A.F.
      A word to the wise about ketamine.
      ), at times likening the field’s enthusiasm to the misguided use of stimulants or opiates to induce short-term depression relief. The rapidity of the antidepressant onset of ketamine (2 hours after infusion) is impressive, but effects also dissipate rapidly (3–7 days). Although the therapeutic benefit far outlasts the drug’s half-life, it is nevertheless too brief for a single infusion to be clinically impactful. Repeated infusions extend the effect but raise concerns regarding safety (e.g., neurocognitive and psychotomimetic side effects), abuse liability, and feasibility. Thus, the future of ketamine research is to identify new treatment strategies—for example, synergistic treatment combinations, pharmacologic alternatives, and novel clinical applications—that will produce more enduring and clinically impactful forms of relief.
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      Linked Article

      • Ketamine as a Prophylactic Against Stress-Induced Depressive-like Behavior
        Biological PsychiatryVol. 79Issue 9
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          Stress exposure is one of the greatest risk factors for psychiatric illnesses like major depressive disorder and posttraumatic stress disorder. However, not all individuals exposed to stress develop affective disorders. Stress resilience, the ability to experience stress without developing persistent psychopathology, varies from individual to individual. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced psychiatric disorders. Despite this fact, no resilience-enhancing pharmaceuticals have been identified.
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