title: A randomized, double-blind, placebo-controlled study of the safety and tolerability of high-dose quetiapine in patients with persistent symptoms of schizophrenia or schizoaffective disorder.
abstract: OBJECTIVE
  Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d.
  
  
  METHODS
  A trial was carried out from October 2003-September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of moderate severity (< 30% improvement in total Positive and Negative Syndrome Scale score after ≥ 4 weeks of quetiapine). The 8 week, double-blind study compared continuation of quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary outcomes were adverse events, metabolic side effects, and symptom severity.
  
  
  RESULTS
  Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high-dose group was 3.1% greater (95% CI, -7.8% to 14.0%; P = .76) than in the 800-mg/d group, a value that was within the a priori limit of 16% defined as noninferiority. Both doses of quetiapine were safe and well tolerated. Weight gain was greater in the high-dose group (1.7 kg over 12 weeks; ≥ 7% body weight, n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; ≥ 7% body weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was greater in the high-dose group (95% CI, 0.0-2.5; P = .044). Symptom severity declined, with no significant difference between groups.
  
  
  CONCLUSIONS
  The results did not demonstrate any advantage for use of quetiapine outside the approved dose range.
  
  
  BACKGROUND
  www.clinicaltrials.gov Identifier: NCT00328978.
authors: BC Mental Health and Addictions Research Institute, Vancouver, Canada. honer@interchange.ubc.ca
authors: William G
authors: WG
authors: Honer
authors: G William
authors: GW
authors: MacEwan
authors: Alain
authors: A
authors: Gendron
authors: Emmanuel
authors: E
authors: Stip
authors: Alain
authors: A
authors: Labelle
authors: Richard
authors: R
authors: Williams
authors: Hans
authors: H
authors: Eriksson
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate