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The Use of Ketamine for the Treatment of Depression in the Context of Psychotic Symptoms

To the Editor:
  • Carolina Medeiros da Frota Ribeiro
    Correspondence
    Address correspondence to Carolina Medeiros da Frota Ribeiro, M.D., Federal University of Ceará, Rua Coronel Linhares, 170, apt 1001 Meireles, Fortaleza, Ceará, Brazil CEP 60170-240
    Affiliations
    Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Gerard Sanacora
    Affiliations
    Departments of Psychiatry and Nursing; Yale Depression Research Program; and Intensive Outpatient Program, Adult Inpatient Service, and Electroconvulsive Therapy Service, Yale–New Haven Psychiatric Hospital, Yale School of Medicine, New Haven, Connecticut
    Search for articles by this author
  • Ralph Hoffman
    Affiliations
    Departments of Psychiatry and Nursing; Yale Depression Research Program; and Intensive Outpatient Program, Adult Inpatient Service, and Electroconvulsive Therapy Service, Yale–New Haven Psychiatric Hospital, Yale School of Medicine, New Haven, Connecticut
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  • Robert Ostroff
    Affiliations
    Federal University of Ceará, Fortaleza, Ceará, Brazil
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      Mounting evidence from a series of small clinical trials and case series suggests ketamine can have rapid and robust antidepressant (
      • McGirr A.
      • Berlim M.T.
      • Bond D.J.
      • Fleck M.P.
      • Yatham L.N.
      • Lam R.W.
      A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes.
      ) and possibly antisuicidal effects (
      • Price R.B.
      • Iosifescu D.V.
      • Murrough J.W.
      • Chang L.C.
      • Al Jurdi R.K.
      • Iqbal S.Z.
      • et al.
      Effects of ketamine on explicit and implicit suicidal cognition: A randomized controlled trial in treatment-resistant depression.
      ) in patients who did not respond to standard treatment options. However, because of the variable psychotomimetic effects of ketamine in healthy volunteers and exacerbation of previously experienced positive symptoms in schizophrenic volunteers (
      • Xu K.
      • Krystal J.H.
      • Ning Y.
      • Chen D.C.
      • He H.
      • Wang D.
      • et al.
      Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia.
      ,
      • Lahti A.C.
      • Weiler M.A.
      • Tamara Michaelidis B.A.
      • Parwani A.
      • Tamminga C.A.
      Effects of ketamine in normal and schizophrenic volunteers.
      ), patients previously experiencing psychotic features have been excluded from the reported studies and trials. We have used ketamine as an antidepressant on several occasions in patients with severe treatment-resistant major depressive episodes with good results. Recently, after seriously considering the risks and benefits of providing off-label ketamine treatment (.5 mg/kg continuous intravenous infusion over 40 minutes) based on this knowledge, we treated two patients with psychotic features complicating severe depressive episodes. To our knowledge, this is the first report describing the use of ketamine as treatment in patients with a history of psychosis.
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      References

        • McGirr A.
        • Berlim M.T.
        • Bond D.J.
        • Fleck M.P.
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        A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes.
        Psychol Med. 2015; 45: 693-704
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        • et al.
        Effects of ketamine on explicit and implicit suicidal cognition: A randomized controlled trial in treatment-resistant depression.
        Depress Anxiety. 2014; 31: 335-343
        • Xu K.
        • Krystal J.H.
        • Ning Y.
        • Chen D.C.
        • He H.
        • Wang D.
        • et al.
        Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia.
        J Psychiatr Res. 2015; 61: 64-72
        • Lahti A.C.
        • Weiler M.A.
        • Tamara Michaelidis B.A.
        • Parwani A.
        • Tamminga C.A.
        Effects of ketamine in normal and schizophrenic volunteers.
        Neuropsychopharmacology. 2001; 25: 455-467
        • Ostroff R.
        • Gonzales M.
        • Sanacora G.
        Antidepressant effect of ketamine during ECT.
        Am J Psychiatry. 2005; 162: 1385-1386

      Linked Article

      • Ketamine and Psychosis History: Antidepressant Efficacy and Psychotomimetic Effects Postinfusion
        Biological PsychiatryVol. 82Issue 5
        • Preview
          da Frota Ribeiro et al. (2016) reported successful treatment of two cases of psychotic depression with intravenous ketamine. Ketamine administration lessened both depressive and psychotic symptoms within hours (1). While ketamine has been shown to have rapid and robust antidepressant effects in numerous trials (2), it has also been associated with increased psychotic symptoms in healthy controls and in those with schizophrenia during and shortly after infusion (3,4). Because of a theoretical risk of exacerbating psychosis in predisposed patients, subjects with current psychotic symptoms or a past history of psychosis are typically excluded from ketamine trials.
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