title: When can patients with potentially life-threatening adverse effects be rechallenged with clozapine? A systematic review of the published literature.
abstract: BACKGROUND
  Clozapine is widely prescribed for treatment refractory patients with schizophrenia, but its use is limited by potentially life threatening adverse effects. Rechallenge after these complications has been occasionally attempted in patients with severe psychotic symptoms.
  
  
  OBJECTIVE
  To review the outcome of clozapine rechallenge after potentially life threatening adverse effects.
  
  
  METHODS
  Electronic, all-language, literature search (1972-2011) followed by demographic and clinical data extraction. The outcome of rechallenge was considered favorable when the lower bound of the 95% confidence interval (CI) of the proportion of patients who could continue clozapine was >50%.
  
  
  RESULTS
  Altogether, 138 patients (mean age: 36.3years, 65.7% male, 57.6% Caucasian, virtually all with schizophrenia spectrum diagnosis) underwent clozapine rechallenge after developing neutropenia (n=112), agranulocytosis (n=15), neuroleptic malignant syndrome (NMS) (n=5), myocarditis (n=4), pericarditis (n=1) and lupus erythematosus (n=1). Rechallenge strategies were heterogeneous and not systematically evaluated. Clozapine rechallenge was successful in 78/112 patients (69.6%, CI: 60.6-77.4) after neutropenia, 3/15 (20%, CI: 7.1-45.2) after agranulocytosis, 5/5 (100%, CI: 56-100) after NMS, 3/4 (75%, CI: 30-95) after myocarditis, 1/1 after pericarditis, and 0/1 after clozapine-induced lupus. Successfully rechallenged patients were followed for 16-96weeks. None of the rechallenged patients died.
  
  
  CONCLUSIONS
  Although controlled studies are clearly needed, using a priori, confidence interval-based criteria, case reports/series suggest that in refractory patients who benefited from clozapine, careful rechallenge can be considered after neutropenia and NMS, but not after agranulocytosis and myocarditis.
authors: The Zucker Hillside Hospital, North Shore - Long Island Jewish Health System, Glen Oaks, New York, United States.
authors: Peter
authors: P
authors: Manu
authors: Deepak
authors: D
authors: Sarpal
authors: Owen
authors: O
authors: Muir
authors: John M
authors: JM
authors: Kane
authors: Christoph U
authors: CU
authors: Correll
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000139:chemically induced* / Q000188:drug therapy; D009459:Neuroleptic Malignant Syndrome / Q000188:drug therapy / Q000209:etiology*; D009503:Neutropenia / Q000139:chemically induced* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine