Psychiatric safety of ketamine in psychopharmacology research.
BACKGROUND
A growing number of investigators are studying ketamine effects in healthy human subjects, but concerns remain about its safety as a research tool. Therefore, it is timely to revisit the safety of subanesthetic doses of ketamine in experimental psychopharmacology studies.


OBJECTIVE
To report on the safety of laboratory studies with subanesthetic doses of ketamine in healthy humans using an existing dataset.


METHODS
Medically healthy subjects with no personal or familial Axis I psychotic spectrum disorders were administered subanesthetic doses of ketamine by intravenous infusion in a series of clinical investigations from 1989 to 2005. The safety of ketamine administration was monitored in these subjects.


RESULTS
Four hundred and fifty subjects received at least one dose of active ketamine. Eight hundred and thirty three active ketamine and 621 placebo infusions were administered. Ten adverse mental status events were documented in nine subjects/infusions that were deemed related to ketamine administration (2% of subjects, 1.45% of infusions). All but one adverse reaction resolved by the end of the test session. The side effects in the remaining individual were no longer clinically significant within 4 days of the test session. No residual sequelae were observed.


CONCLUSIONS
Ketamine administration at subanesthetic doses appears to present an acceptable level of risk for carefully screened populations of healthy human subjects in the context of clinical research programs that intensively monitor subjects throughout their study participation.
Perry
Edward B
EB
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Cramer
Joyce A
JA
Cho
Hyun-Sang
HS
Petrakis
Ismene L
IL
Karper
Laurence P
LP
Genovese
Angelina
A
O'Donnell
Elizabeth
E
Krystal
John H
JH
D'Souza
D Cyril
DC
D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced*; D008875:Middle Aged; D011600:Psychopharmacology; D012306:Risk
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine