Subanesthetic doses of ketamine stimulate psychosis in schizophrenia.
Adrienne C. Lahti, B Koffel, D LaPorte, Carol A. Tamminga
Neuropsychopharmacology August 1, 1995 DOI: 10.1016/0893-133x(94)00131-i (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled experimental study Peer reviewed |
|---|---|
| Population | Individuals with schizophrenia |
| Interventions | Ketamine haloperidol |
| Dose | 0.1, 0.3, and 0.5 mg/kg |
| Duration | Short (< 30 minutes) worsening in mental status; retested after being neuroleptic-free for 4 weeks; delayed or prolonged (8-24 hours) psychotomimetic effects |
| Measures | BPRS total score |
| Topics | Ketamine Esketamine |
| Keywords | Humans Psychoses, substance-induced Haloperidol Glutamic acid Injections, intravenous Double-blind method Schizophrenia Dose-response relationship, drug Time factors Adult Middle aged Female |
| Key findings | Ketamine produced a dose-related, short-lived worsening of psychotic symptoms in people with schizophrenia, mainly positive symptoms, with significant BPRS increases at 0.3 mg/kg and 0.5 mg/kg. Retesting six patients after four weeks without neuroleptics did not indicate that haloperidol blocks ketamine-induced psychosis. The authors suggest that antagonism of NMDA-sensitive glutamatergic transmission exacerbates schizophrenia symptoms. |
Abstract
We administered ketamine to schizophrenic individuals in a double-blind, placebo-controlled design using a range of subanesthetic doses (0.1, 0.3, and 0.5 mg/kg) to evaluate the nature, dose characteristics, time course, and neuroleptic modulation of N-methyl-D-aspartate (NMDA) antagonist action on mental status in schizophrenia. Ketamine induced a dose-related, short (< 30 minutes) worsening in mental status in the haloperidol-treated condition, reflected by a significant increase in BPRS total score for the 0.3 mg/kg (p = .005) and 0.5 mg/kg (p = .01) challenges. Positive symptoms (hallucinations, delusions, thought disorder), not negative symptoms accounted for these changes. These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject's symptoms during active episodes of their illness. Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis. Several subjects evidenced delayed or prolonged (8-24 hours) psychotomimetic effects such as worsening of psychosis with visual hallucinations. These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia.
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
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- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats Science August 28, 1998
- Ketamine use: a review Addiction July 21, 2011
- Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine Archives of General Psychiatry March 1, 2000
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
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Cites 9
- 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
- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
- CLINICAL REACTIONS OF SCHIZOPHRENICS TO SODIUM AMYTAL, PERVITIN HYDROCHLORIDE, MESCALINE SULFATE, AND D-LYSERGIC ACID DIETHYLAMIDE (LSD25) The Journal of Nervous and Mental Disease February 1, 1954
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