title: Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study.
abstract: BACKGROUND
  The aim of this study was to evaluate the long-term efficacy and safety of clozapine in patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features.
  
  
  METHODS
  101 patients with a DSM-III-R diagnosis of schizophrenia (N = 34); schizoaffective disorder, bipolar type (N = 30); or bipolar disorder with psychotic features (N = 37) were naturalistically treated with clozapine at flexible doses over a 48-month period. Data were collected from 1994 to 2000. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness scale total predicted scores over time were estimated with random-effects regression models. Time to response to clozapine, defined as 50% reduction of BPRS score, was analyzed in the 3 diagnostic groups using the Kaplan-Meier method. Survival curves were compared using the log-rank test.
  
  
  RESULTS
  The BPRS total predicted score halved its baseline value in 3 months for bipolar disorder patients, in 6 months for schizoaffective disorder patients, and in 24 months for schizophrenia patients. The proportion of subjects who satisfied the criterion for response to clozapine after 48 months of follow-up was significantly (p <.01) higher in the schizoaffective and bipolar disorder groups (90.0% and 83.8%, respectively) than in the schizophrenia group (64.7%). Baseline scores on the Global Assessment of Functioning (GAF) showed low levels of psychosocial and occupational functioning in all 3 groups. After 48 months of treatment, GAF scores showed a functional improvement in all 3 groups, with significantly (p <.01) greater improvement in the bipolar disorder group compared with the other groups.
  
  
  CONCLUSIONS
  The findings of this study confirm the efficacy and safety of clozapine for treatment-resistant patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Patients with schizoaffective disorder and those with bipolar disorder show greater clinical improvement than those with schizophrenia. Patients with bipolar disorder have the shortest time to response and the highest psychosocial and occupational functioning levels. Patients with schizoaffective disorder have the lowest treatment discontinuation rate.
authors.affiliation: Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology, University of Pisa, Italy. ciapparelli.a@tin.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Ciapparelli
authors.forename: Liliana
authors.initials: L
authors.lastname: Dell'Osso
authors.forename: Adolfo
authors.initials: A
authors.lastname: Bandettini di Poggio
authors.forename: Claudia
authors.initials: C
authors.lastname: Carmassi
authors.forename: Donatella
authors.initials: D
authors.lastname: Cecconi
authors.forename: Melania
authors.initials: M
authors.lastname: Fenzi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Chiavacci
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.forename: Carla E
authors.initials: CE
authors.lastname: Ramacciotti
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Cassano
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D010054:Brief Psychiatric Rating Scale; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine