title: Long-term outcome of patients who receive ketamine during research.
abstract: BACKGROUND
  To comprehend the pathophysiology of schizophrenia and to facilitate drug discovery, animal and human models of schizophrenia are necessary. Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has been used to probe glutamatergic function in normal and schizophrenic volunteers. These studies and others have provided data consistent with a putative involvement of a glutamatergic dysfunction in the pathophysiology of schizophrenia; however, these studies have also raised concerns about the distress inflicted on patients, the potential for adverse events, and the serious long-term effects that could possibly be induced by symptom-simulating action.
  
  
  METHODS
  For all patient volunteers (n = 30) who participated in these studies, we reviewed the acute safety during and in the immediate postketamine administration. Patients available for long-term follow-up (n = 25) were matched to a group of patients (n = 25) who participated in research but did not receive ketamine. We compared their long-term outcome in terms of psychopathology, the need for psychiatric care, and the amount of antipsychotic medication required for optimal therapeutic response.
  
  
  RESULTS
  There were no serious adverse events in more than 90 ketamine interviews. Distress to patients was minimal, which is shown by the lack of anxiety ratings. Over a mean follow-up period of 8 months, we found no differences between patients who did and did not receive ketamine on any measures of psychopathology, psychiatric care, or the amount of antipsychotic medication.
  
  
  CONCLUSIONS
  In a controlled environment and paying close attention to subject safety features, administering subanesthetic doses of ketamine causes no adverse events and little distress to schizophrenic volunteers. This study strongly indicates that administering ketamine does not change any aspect of the course of schizophrenic illness.
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Lahti
authors.forename: D
authors.initials: D
authors.lastname: Warfel
authors.forename: T
authors.initials: T
authors.lastname: Michaelidis
authors.forename: M A
authors.initials: MA
authors.lastname: Weiler
authors.forename: K
authors.initials: K
authors.lastname: Frey
authors.forename: C A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D007649:Ketamine