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Psychiatric safety of ketamine in psychopharmacology research

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Abstract

Rationale

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.

Materials and 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.

Conclusion

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.

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Acknowledgment

The authors thank Eli Lilly and Company for the provision of LY354740 and administrative and scientific support. The authors thank GlaxoSmithKline for the provision of lamotrigine and administrative and scientific support. The authors also acknowledge support from the Department of Veterans Affairs (Alcohol Research Center and Schizophrenia Biological Research Center). Lastly, the authors thank Sonah Yoo, R.Ph.; Robert Sturwold, R.Ph.; Brenda Breault, R.N., B.S.N.; Gina McManus, R.N.; Sandra Capelli, R.N.; Patricia Barry, R.N.; Cynthia D’Amico, R.N.; Willie Ford; John Roach; and Arthur Flegert of the Neurobiological Studies Unit at the VA Connecticut Healthcare System, West Haven Campus for their central contributions to the success of this project.

The members of the Yale Ketamine Study Group were as follows: Abi-Dargham, A; Abi-Saab, D; Abi-Saab, W; Ammerman, YW; Anand, A; Belger, A; Bennett, A; Berman, RM; Boutros, N; Bowers, MB; Breier, A; Bremner, JD; Brush, L; Cappiello, A; Cassello, K; Charney, DS; Cho, H; Cooney, NL; Cooper, TB; Cramer, J; Damon, D; Delaney, R; D’Souza, DC; Freeman, GK; Gelernter, J; Gil, R; Grillon, C; Gueorguieva, R; Heninger, GR; Hu, XS; Hunsberger, T; Jatlow, P; Karper, LP; Krystal, JH; Levine, L; Limoncelli, D; Lipschitz, DS; Liu, N; MacDougall, L; Madonick, SH; Morrissey, K; Namenworth, S; Oren, DA; Perry, EB; Petrakis, IL; Seibyl, JP; Stetson, P; Suckow, RF; Trevisan, LA; Vegso, S; Webb, E; White, JA; Zimmerman, L; and Zuzarte, E.

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Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Edward B. Perry Jr., Joyce A. Cramer, Hyun-Sang Cho, Ismene L. Petrakis, Laurence P. Karper, John H. Krystal & D. Cyril D’Souza

  2. Schizophrenia Biological Research Center (116A), VA Connecticut Healthcare System, West Haven, CT, USA

    Edward B. Perry Jr., Joyce A. Cramer, Ismene L. Petrakis, Angelina Genovese, Elizabeth O’Donnell, John H. Krystal & D. Cyril D’Souza

  3. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA

    Edward B. Perry Jr., Ismene L. Petrakis, John H. Krystal & D. Cyril D’Souza

  4. Department of Psychiatry, Yonsei University College of Medicine, Seoul, South Korea

    Hyun-Sang Cho

  5. Psychiatry Service (116A), VA Connecticut Healthcare System, West Haven, CT, 06516, USA

    Edward B. Perry Jr.

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  1. Edward B. Perry Jr.
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  2. Joyce A. Cramer
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  3. Hyun-Sang Cho
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  4. Ismene L. Petrakis
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  5. Laurence P. Karper
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  6. Angelina Genovese
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  7. Elizabeth O’Donnell
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  8. John H. Krystal
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  9. D. Cyril D’Souza
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Yale Ketamine Study Group

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Correspondence to Edward B. Perry Jr..

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Other members of the Yale Ketamine Study Group are listed in the Acknowledgements.

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Perry, E.B., Cramer, J.A., Cho, HS. et al. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology 192, 253–260 (2007). https://doi.org/10.1007/s00213-007-0706-2

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  • DOI: https://doi.org/10.1007/s00213-007-0706-2

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