title: Cerebral metabolic changes induced by clozapine in schizophrenia and related to clinical improvement.
abstract: BACKGROUND
  The study of the different effects on brain metabolism between typical and atypical antipsychotics would aid in understanding their mechanisms of action. Clozapine is of special interest, since it is one of the most effective antipsychotic drugs and demonstrates a distinctive mechanism of action in pre-clinical studies with respect to typical neuroleptics.
  
  
  OBJECTIVE
  To study the differences in cerebral activity induced by clozapine as compared to those produced by haloperidol.
  
  
  METHODS
  [18F]Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) scans were obtained in the resting condition before and after 6 months of treatment with clozapine in 22 treatment-resistant patients with schizophrenia. Before inclusion, patients had been chronically treated with classical drugs, and all of them received haloperidol during the last month. Data were analyzed with statistical parametric mapping (SPM'99) methods, comparing pre-treatment and post-treatment conditions. The association between the changes in symptom scores and metabolism was also assessed to corroborate the functional relevance of possible metabolic changes.
  
  
  RESULTS
  Clozapine decreased prefrontal and basal ganglia activity, and increased occipital metabolism, including primary and association visual areas. The change in negative symptoms was related with the decrease of basal ganglia activity; the improvement in disorganization related to the metabolic decrease in the motor area, and the change in positive symptoms was associated to the increase of activity in the visual area.
  
  
  CONCLUSIONS
  These results show that haloperidol and clozapine produce different patterns of metabolic changes in schizophrenia. Compared to the haloperidol baseline, clozapine inhibited the metabolic activity of the prefrontal and motor cortical regions and basal ganglia and induced a higher activation of the visual cortex. The improvement in disorganization, negative and positive syndromes with clozapine may be respectively associated with metabolic changes in the motor area, basal ganglia, and visual cortex.
authors.affiliation: Department of Psychiatry, Hospital Doce de Octubre, Madrid, Spain. vmolinarod@wanadoo.es
authors.forename: Vicente
authors.initials: V
authors.lastname: Molina
authors.forename: Juan D
authors.initials: JD
authors.lastname: Gispert
authors.forename: Santiago
authors.initials: S
authors.lastname: Reig
authors.forename: Javier
authors.initials: J
authors.lastname: Sanz
authors.forename: Javier
authors.initials: J
authors.lastname: Pascau
authors.forename: Andrés
authors.initials: A
authors.lastname: Santos
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
authors.forename: Tomás
authors.initials: T
authors.lastname: Palomo
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol