clozapine and Hypertrophy

Typical antipsychotics have been reported to enlarge the caudate nucleus in schizophrenic patients. The atypical antipsychotic, clozapine, is associated with a decrease in caudate size in patients previously treated with typical antipsychotics. The present study investigates whether a change in caudate volume after switching from treatment with typical antipsychotics to treatment with clozapine is related to improvement in symptoms or tardive dyskinesia (TD). Twenty-six schizophrenic patients participated in this open study. Caudate nucleus volume and TD were assessed before discontinuing typical antipsychotics and after 24 weeks of treatment with clozapine. After discontinuing typical antipsychotics, symptoms were assessed in a 3 days drug-free period and subsequently once a month. Treatment with clozapine resulted in a decrease in caudate volume, improvement in symptoms and amelioration of TD. However, no difference in caudate volume changes was found between responders and non-responders to clozapine and no correlations were found between caudate volume changes and reduction of TD. In conclusion, this study replicates earlier findings that clozapine decreases caudate volume in patients previously treated with typical antipsychotics and suggests that this effect is unrelated to treatment response or to amelioration of TD.

Topics: Adult; Antipsychotic Agents; Caudate Nucleus; Clozapine; Disease Progression; Dyskinesia, Drug-Induced; Female; Humans; Hypertrophy; Magnetic Resonance Imaging; Male; Middle Aged; Schizophrenia; Treatment Outcome

Striatal enlargement has been consistently reported in schizophrenics receiving chronic neuroleptic treatment although the results following atypical antipsychotic treatment have been equivocal. In order to disentangle patient illness from a possible drug effect on brain structure, young adult rats were administered either haloperidol, risperidone, clozapine, olanzapine, or vehicle daily for four or eight months via drinking water. Significant increases in caudate-putamen volumes were seen in animals receiving either haloperidol or clozapine when compared with control animals following eight months of drug administration. Conversely, olanzapine-treated animals showed significant decreases in caudate-putamen volumes when compared with control animals after eight months of drug. Thus, converging evidence indicates that the neuroplastic response of the striatum following neuroleptic exposure causes volumetric increases, whereas atypical antipsychotics affect the basal ganglia differentially. The current data suggests that such differential responses may be due to both the pharmacological properties and the relative doses of the atypical agents.

Topics: Animals; Antipsychotic Agents; Caudate Nucleus; Clozapine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Haloperidol; Hypertrophy; Male; Neostriatum; Neuronal Plasticity; Neurons; Putamen; Rats; Rats, Sprague-Dawley; Risperidone; Schizophrenia; Time Factors

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Hypertrophy; Male; Schizophrenia; Submandibular Gland Diseases