High dose benzodiazepine dependence: description of 29 patients treated with flumazenil infusion and stabilised with clonazepam

Psychiatry Res. 2012 Aug 15;198(3):457-62. doi: 10.1016/j.psychres.2012.02.008. Epub 2012 Mar 17.


The withdrawal syndrome from benzodiazepine (BZD) can be severe and in some cases may impede cessation of the use of the drug. We present here a case series of benzodiazepine detoxification by flumazenil infusion, stabilised with clonazepam. Patients were treated with flumazenil 1.35 mg/day for a median of 7 days. Self-reported physical withdrawal symptoms were recorded daily. In addition to flumazenil, antidepressants were given before treatment commenced and clonazepam was administered nightly with both being continued after discharge. Twenty-nine patients were treated. No patients dropped out from the treatment programme. Nine patients (31%) required a temporary reduction/cessation of the infusion. The linear trend in the reduction of the daily withdrawal scores in the overall study population was significant. The linear trends were also significant in the group of patients for whom a temporary reduction/suspension of the flumazenil was required. Six months after treatment, 15 patients (53%) were abstinent from clonazepam and other BZDs. For five (21%) the BZD dependence were reinstated. More than two-thirds of the subjects tolerated the procedure well and about half had a good long term response. Slow flumazenil infusion appears to merit consideration as a possible future treatment. Suggestions for future research are examined.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use*
  • Clonazepam / therapeutic use*
  • Drug Therapy, Combination / methods
  • Female
  • Flumazenil / administration & dosage*
  • GABA Modulators / administration & dosage
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance-Related Disorders / drug therapy*


  • Antidepressive Agents
  • GABA Modulators
  • Benzodiazepines
  • Flumazenil
  • Clonazepam