title: Rapid clozapine titration in treatment-refractory bipolar disorder.
abstract: BACKGROUND
  Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data.
  
  
  OBJECTIVE
  To evaluate the safety and effectiveness of rapid clozapine titration in BD.
  
  
  METHODS
  Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features.
  
  
  RESULTS
  Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077).
  
  
  CONCLUSIONS
  Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method.
authors.affiliation: Faculty of Medicine, Transilvania University, Brasov, Romania.
authors.forename: Petru
authors.initials: P
authors.lastname: Ifteni
authors.affiliation: Zucker Hillside Hospital, Glen Oaks, NY, USA; Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Aalborg University Hospital, Psychiatry, Aalborg, Denmark; Clinical Department of Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Jimmi
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Faculty of Medicine, Transilvania University, Brasov, Romania.
authors.forename: Victoria
authors.initials: V
authors.lastname: Burtea
authors.affiliation: Zucker Hillside Hospital, Glen Oaks, NY, USA; Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.affiliation: Zucker Hillside Hospital, Glen Oaks, NY, USA; Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: pmanu@nshs.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Manu
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003024:Clozapine / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D003631:Day Care, Medical; D004334:Drug Administration Schedule; D005260:Female; D006760:Hospitalization; D006778:Hospitals, Psychiatric; D006801:Humans; D007902:Length of Stay; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Bipolar disorder; Clozapine; Discharge; Rapid titration; Symptom control; Tolerability