clozapine and Brain-Injuries

Topics: Antipsychotic Agents; Brain Injuries; Clozapine; Cognition Disorders; Drug Therapy, Combination; Employment, Supported; Humans; Piperazines; Schizophrenia; Thiazoles

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Brain Injuries; Clozapine; Hippocampus; Male; Maze Learning; Memory; Microinjections; N-Methylaspartate; Neurotoxins; Rats; Rats, Sprague-Dawley; Space Perception; Spatial Behavior; Statistics, Nonparametric; Time Factors

Violent behavior is a significant problem in the psychiatric hospital setting. Persistently violent patients often require seclusion and/or restraints and typically receive high doses of medication and polypharmacy. Clozapine has been found to be effective in reducing aggression in patients with psychosis. Thus, we examined the effects of clozapine in a heterogeneous group of persistently violent patients. A chart review of the effect of clozapine in persistently violent patients was performed. Changes in the number of violent episodes and the need for seclusion and restraint were assessed for a 3-month period before and after receiving clozapine. In this group of five, carefully selected, persistently violent patients, clozapine treatment resulted in marked decreases in violent episodes and the use of seclusion and restraint. These data suggest a role for clozapine in the treatment of persistently violent patients irrespective of DSM-IV diagnosis.

Topics: Adolescent; Adult; Analysis of Variance; Brain Injuries; Clozapine; Female; Humans; Male; Meningitis; Mental Disorders; Retrospective Studies; Violence

Topics: Antipsychotic Agents; Brain Injuries; Catatonia; Clozapine; Female; Frontal Lobe; Humans; Middle Aged