Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Oct 1997
Randomized Controlled Trial Clinical TrialClozapine blunts N-methyl-D-aspartate antagonist-induced psychosis: a study with ketamine.
Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in the antipsychotic efficacy of the atypical antipsychotic agent clozapine. Clinical data on the interaction between clozapine's mechanism of action and NMDA receptor function have been lacking secondary to a paucity of pharmacologic probes of the NMDA system. We have utilized a double-blind, placebo-controlled infusion paradigm with subanesthetic doses of the NMDA antagonist ketamine to test the hypothesis that clozapine would blunt ketamine-induced psychotic symptoms in schizophrenic patients. ⋯ Antipsychotic drug-free patients experienced increases in ratings of positive and negative symptoms. Clozapine treatment significantly blunted the ketamine-induced increase in positive symptoms. These data suggest that NMDA receptor function may be involved in the unique antipsychotic efficacy of clozapine.
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Neuropsychopharmacology · Sep 1997
Case Reports Clinical TrialSynergism of lorazepam and electroconvulsive therapy in the treatment of catatonia.
Electroconvulsive therapy (ECT) and lorazepam are effective treatments for catatonia. ECT combined with benzodiazepines has been associated with reduced efficacy and efficiency and therefore is not recommended in the routine practice of ECT. ⋯ In each case, the combination of lorazepam with ECT was superior to monotherapy. This apparent synergism, its possible mechanisms, and its implications for treating catatonia are discussed.
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Neuropsychopharmacology · Jun 1997
Delta 9-tetrahydrocannabinol increases prefrontal cortical catecholaminergic utilization and impairs spatial working memory in the rat: blockade of dopaminergic effects with HA966.
The present study examined delta 9-tetrahydrocannabinol (THC)-induced alterations in monoamine transmission in the rat forebrain as well as the effects of the enantiomers of 3-amino-1-hydroxypyrrolid-2-one (HA966) on the monoamine response to THC. Activation of dopamine (DA) and norepinephrine (NE) but not serotonin (5-HT) turnover in the prefrontal cortex (PFC) was observed after THC (5 mg/kg i.p.) administration. Both enantiomers of HA966 completely prevented the effects of THC on PFC DA turnover and partially blocked the THC-induced rise in NE metabolism. ⋯ THC significantly impaired spatial working, but not reference, memory in rats, and this effect was ameliorated by HA966. Thus, HA966 prevents the THC-induced increases in PFC DA turnover and impairments of prefrontal cortical working memory function. Furthermore, these data suggest that cognitive impairments displayed by marijuana self-administering humans may be related to PFC DA hyperactivity and that HA966 may prevent this effect.
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Neuropsychopharmacology · Jan 1997
Randomized Controlled Trial Clinical TrialEffects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder.
The effects of treatment with serotonin (5-HT) reuptake inhibitors on platelet 5-HT2 receptors, 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors (SSRI), paroxetine, and fluoxetine, for the treatment of major depression. Hamilton Depression Rating Scale (HAM-D) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline, after 4 and 8 weeks of treatment, and were compared to 21 healthy controls. Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites, labelled with [3H]paroxetine, or 5-HT2 receptors, labelled with [3H]LSD. ⋯ Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively. These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation. Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy, particularly in suicidal depressed patients.
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Neuropsychopharmacology · Jun 1996
Randomized Controlled Trial Clinical TrialThe effects of chronic naltrexone treatment in young autistic children: a double-blind placebo-controlled crossover study.
In a double-blind placebo-controlled crossover trial 23 autistic children, aged 3-7 years, were treated with a mean daily dosage of 1 mg/kg naltrexone for 4 weeks. Drug effects were monitored with behavior checklists rated by parents and teachers, and ethological playroom observations. ⋯ They reported a decrease in hyperactivity and irritability. No effects of naltrexone on social and stereotypic behavior could be demonstrated.