Clinical and sensorimotor gating effects of ketamine in normals.
E J Duncan, S H Madonick, A Parwani, B Angrist, R Rajan, S Chakravorty, T R Efferen, S Szilagyi, M Stephanides, P B Chappell, S Gonzenbach, G N Ko, J P Rotrosen
Neuropsychopharmacology July 1, 2001 DOI: 10.1016/s0893-133x(00)00240-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized double-blind crossover design Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy male subjects |
| Interventions | Ketamine normal saline |
| Dose | 0.5 mg/kg |
| Duration | 60-minute infusion |
| Topics | Esketamine Ketamine |
| Key points | Ketamine enhanced prepulse inhibition rather than disrupting it, indicating its clinical effects are not coupled with schizophrenic-like PPI disruption. |
Abstract
The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated schizophrenic patients. The amplitudes of the startle responses to pulse-alone stimuli were not significantly different on ketamine and placebo days. Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls.
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 18
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- To use or not to use: an update on licit and illicit ketamine use Substance Abuse and Rehabilitation March 1, 2011
- Is the Acute NMDA Receptor Hypofunction a Valid Model of Schizophrenia? Schizophrenia Bulletin September 28, 2011
- Ketamine Disrupts Frontal and Hippocampal Contribution to Encoding and Retrieval of Episodic Memory: An fMRI Study Cerebral Cortex November 10, 2004
and 13 more in the library
Cites 10
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- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Observations on the Action of Sernyl — A New Psychotropic Drug Canadian Psychiatric Association Journal June 1, 1961
and 5 more in the library