title: Safety evaluation of the concomitant use of clozapine and benzodiazepines: a retrospective, cross-sectional chart review.
abstract: OBJECTIVE
  Previously published case reports have noted severe adverse reactions such as cardiac arrest, respiratory arrest, and sudden death when clozapine (CLZ) and benzodiazepines (BZDs) are used concomitantly. As CLZ and BZD are both used regularly to treat psychiatric illness, it is important to have additional information concerning this potential interaction. The objective of this study was to contribute to the evolving literature by evaluating the occurrence of sudden deaths and cardiac or respiratory events leading to death in patients treated concurrently with CLZ and BZD.
  
  
  METHODS
  A retrospective chart review was conducted at a 240-bed New York State mental health facility. Most patients in this facility have been diagnosed with refractory schizophrenia, resulting in high rates of CLZ use. Electronic and hard copy records of the 490 patients who had been treated with CLZ in this facility at any time from 2001 to 2006 were selected, and the medication records of these patients were assessed for concomitant BZD use. Information on 152 patients who were treated with CLZ and a BZD concomitantly during this time period are included in this study. Data from the facility's mortality review committee were obtained to determine sudden deaths and cardiac or respiratory events leading to death in patients treated with CLZ and BZD concomitantly. Secondary parameters also recorded during the chart review included average duration of CLZ therapy, BZD therapy, and concomitant therapy; average doses of agents used; specific BZD used; number of patients treated with a specific BZD; psychiatric diagnosis; and use of other medications that depress the central nervous system.
  
  
  CONCLUSIONS
  No deaths occurred as a result of concomitant BZD and CLZ use in the sample examined in this study, suggesting that CLZ and BZD may be safely used concomitantly in many cases. Further study is needed to determine patient characteristics or predisposing factors that might put patients at higher risk of death from this interaction. Our findings are limited by the small sample size and suboptimal frequency of side effect measurements (e.g., measurements of blood pressure and heart rate, reports of hypotensive episodes). Confounding variables that might also play a role in interactions between CLZ and BZDs, but which were not measured in this study, include other types of respiratory compromise, cognitive dysfunction, and organ dysfunction. Precautionary measures that may be used when initiating concomitant CLZ and BZD therapy include slow titration of CLZ, blood pressure monitoring, and/or nightly pulse oximeter measurements.
authors.affiliation: State University of New York at Buffalo, NY, USA. becky.bitter@gmail.com
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bitter
authors.forename: Tammie Lee
authors.initials: TL
authors.lastname: Demler
authors.forename: Lewis
authors.initials: L
authors.lastname: Opler
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006323:Heart Arrest / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008499:Medical Records / Q000706:statistics & numerical data*; D008875:Middle Aged; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine