Effects of ketamine in normal and schizophrenic volunteers

Adrienne C. Lahti; Martin A. Weiler; Tamara Michaelidis; Arti Parwani; Carol A. Tamminga

doi:10.1016/S0893-133X(01)00243-3

Effects of ketamine in normal and schizophrenic volunteers

Adrienne C. Lahti, Martin A. Weiler, Tamara Michaelidis, Arti Parwani, Carol A. Tamminga

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557 Scopus citations

Abstract

This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p = .0001) and the BPRS withdrawal subscale (p = .0001), whereas SVs experienced an increase only in positive symptoms (p = .0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.

Original language	English (US)
Pages (from-to)	455-467
Number of pages	13
Journal	Neuropsychopharmacology
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/S0893-133X(01)00243-3
State	Published - 2001

Keywords

Drug model
Glutamate
Ketamine
N-methyl-D-aspartate
Psychosis
Schizophrenia

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health

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10.1016/S0893-133X(01)00243-3

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@article{5aedcebd94824d7da80e0ebc31e08c13,

title = "Effects of ketamine in normal and schizophrenic volunteers",

abstract = "This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p = .0001) and the BPRS withdrawal subscale (p = .0001), whereas SVs experienced an increase only in positive symptoms (p = .0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.",

keywords = "Drug model, Glutamate, Ketamine, N-methyl-D-aspartate, Psychosis, Schizophrenia",

author = "Lahti, {Adrienne C.} and Weiler, {Martin A.} and Tamara Michaelidis and Arti Parwani and Tamminga, {Carol A.}",

note = "Funding Information: This ketamine research was supported in part by grant DA09483 and for subject characteristic by MH40279. The authors thank all of the schizophrenic and normal volunteers who took part in these research studies, the staff of the Residential Research Unit of the Maryland Psychiatric Research Center, Kristin Frey Deb Medoff and Bob McMahon for statistical expertise, Thomas Cooper for plasma ketamine assays determination, and Kristin Ricasa for her administrative assistance.",

year = "2001",

doi = "10.1016/S0893-133X(01)00243-3",

language = "English (US)",

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pages = "455--467",

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T1 - Effects of ketamine in normal and schizophrenic volunteers

AU - Lahti, Adrienne C.

AU - Weiler, Martin A.

AU - Michaelidis, Tamara

AU - Parwani, Arti

AU - Tamminga, Carol A.

N1 - Funding Information: This ketamine research was supported in part by grant DA09483 and for subject characteristic by MH40279. The authors thank all of the schizophrenic and normal volunteers who took part in these research studies, the staff of the Residential Research Unit of the Maryland Psychiatric Research Center, Kristin Frey Deb Medoff and Bob McMahon for statistical expertise, Thomas Cooper for plasma ketamine assays determination, and Kristin Ricasa for her administrative assistance.

PY - 2001

Y1 - 2001

N2 - This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p = .0001) and the BPRS withdrawal subscale (p = .0001), whereas SVs experienced an increase only in positive symptoms (p = .0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.

AB - This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p = .0001) and the BPRS withdrawal subscale (p = .0001), whereas SVs experienced an increase only in positive symptoms (p = .0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.

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KW - N-methyl-D-aspartate

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IS - 4

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Effects of ketamine in normal and schizophrenic volunteers

Abstract

Keywords

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