The monograph by Malcolm Lader [1] published recently in this journal is certainly a comprehensive and authoritative work of reference on the subject of benzodiazepines (BZDs). In his conclusions, Lader strongly recommends further development of the method using slow infusion of flumazenil (FLU-SI) in patients withdrawing from BZDs. We agree wholeheartedly with this, but also wish to offer the following reflections in response to the author's invitation to open a debate.

The first study of the efficacy of FLU-SI dates back to 20 years ago [1]. One can only wonder why an innovative method which is rapid and effective has been so little used or studied over such a long period, despite the high prevalence and importance of BZD dependence. The clinical studies of FLU-SI published since 1992 can be counted on the fingers of one hand [1]. Furthermore, we believe that very few centres in the world—perhaps four or five?—offer this method to their patients.

We started using FLU-SI in 2003, never imagining that within less than 3 years it would become the principal activity of our Addiction Unit, involved in more than 50% of requests for admission for detoxification [2]. Since then it has been used to treat more than 300 patients, including many doctors, dependent on high doses of BZD [high-dose dependent (HDDs), with an average consumption 70 times higher than the defined daily doses (DDDs)].

Suggesting gradual tapering of the dose to such HDD patients is like suggesting that alcoholics gradually stop drinking: it simply does not work, and the problem is aggravated, in the case of BZDs, by the very long time that tapering takes. The crucial point is that these HDDs have been the subject of very little study and are virtually ignored in research and clinical practice, which tend to be confined to patients with co-addictions and personality disorders; but the situation is more complex. The capacity of BZDs to create tolerance, along with their low toxicity, can induce truly stupefying increments in dosage [3].

FLU-SI works best with HDD patients, but specialists are not trying it: there have probably been too few scientific studies for it to be considered ‘good practice’. Perhaps the congress format, with a clearer emphasis on experience, would be the most appropriate for promoting this method, but there have been no congresses about BZDs for years, at least in Italy. Pharmaceutical companies have no interest in highlighting these phenomena: all the old molecules are still the best-sellers. Even at conferences on addiction or psychiatry little is said about BZDs, and even less about FLU-SI, although the method also works very well in situations of co-addiction and in patients with personality disorders [4].

Before FLU-SI can become a routine therapy, further investigation is needed of the FLU dosage, the duration of infusion, safety issues in an out-patient setting due to the risk of seizures and measures for preventing them [2,5]. The current situation of prevalence and negligence should not be allowed to continue. After all, BZD addiction is the most typical form of iatrogenic dependence; or is that the real reason for the lack of interest in it?


  1. Top of page
  2. Declarations of interest
  3. References