title: Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia.
abstract: Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary. bitter@psych.sote.hu
authors.forename: Istvan
authors.initials: I
authors.lastname: Bitter
authors.forename: Martin R K
authors.initials: MR
authors.lastname: Dossenbach
authors.forename: Shlomo
authors.initials: S
authors.lastname: Brook
authors.forename: Peter D
authors.initials: PD
authors.lastname: Feldman
authors.forename: Stephen
authors.initials: S
authors.lastname: Metcalfe
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Gagiano
authors.forename: János
authors.initials: J
authors.lastname: Füredi
authors.forename: György
authors.initials: G
authors.lastname: Bartko
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Janka
authors.forename: Csaba M
authors.initials: CM
authors.lastname: Banki
authors.forename: Gabor
authors.initials: G
authors.lastname: Kovacs
authors.forename: Alan
authors.initials: A
authors.lastname: Breier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000209:etiology; D001569:Benzodiazepines; D001835:Body Weight / Q000187:drug effects; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D000077152:Olanzapine