Effects of ketamine in normal and schizophrenic volunteers.
Adrienne C. Lahti, M A Weiler, B A Tamara Michaelidis, A Parwani, Carol A. Tamminga
Neuropsychopharmacology October 1, 2001 DOI: 10.1016/s0893-133x(01)00243-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Normal volunteers and schizophrenic volunteers |
| Intervention | Ketamine |
| Dose | 0.1-0.5 mg/kg; 0.3 mg/kg |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine induced a dose-related, short increase in psychotic symptoms in both groups, with similar magnitude of positive-symptom change and superimposable dose-response profiles over time. |
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.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 89
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry April 5, 2017
- Ketamine alters oscillatory coupling in the hippocampus Scientific Reports August 2, 2013
and 84 more in the library
Cites 10
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
and 5 more in the library