Megadose bromazepam and zolpidem dependence: two case reports of treatment with flumazenil and valproate.
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ABSTRACT: INTRODUCTION Insomnia is a commonly reported clinical symptom. The annual prevalence of insomnia symptoms has been reported to range from 35–50% of the population, 1 including cases of in-somnia disorders occurring at 10–22%, 2,3 although the exact frequency depends on the diag-nostic criteria applied. The prevalence of insomnia symptoms in Korea was reported to be 17– 23%, 4,5 including Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis in 5% of the patients. 4 Insomnia is predictive of psychiatric disorders, including de-pression, anxiety disorders, and alcohol or drug abuse, and is also associated with physical function and quality of life. The prevalence of insomnia is greater in the elderly population. 4,5 Insomnia shows a female predisposition which is consistent and progressive with age, becom-ing more prevalent in the elderly. 6 Additionally, it has been reported that chronic benzodiaze-pine or hypnotic drug users are most often elderly. 7,8 The pharmacokinetics and clearance of hypnotic drugs may be altered in elderly individuals compared to younger individuals. It is well known that benzodiazepine, which has a long half-life, may be associated with an in-creased incidence of adverse events, such as confusion or falling down, among the elderly. 9-11 Several hypnotic drugs have been approved by the Korean Food and Drug Administration (KFDA). Physicians can also prescribe many hypnotic medications for insomnia without KFDA indication, including antipsychotics, benzodiazepine, and sedative antidepressants such as am-itriptyline and trazodone antihistamine. Many people who suffer from sleep problems do not Correspondence Background and ObjectiveaaThis study aimed to characterize patterns of hypnotic drug prescription based on age and gender using data from the Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) of South Korea.Sleep Medicine Research. 01/2013; 4(2):51-55.
- British Journal of Clinical Pharmacology 04/2013; · 3.69 Impact Factor
Letter to the Editoradd_38511
WHAT IS STOPPING US FROM
The monograph by Malcolm Lader  published recently
in this journal is certainly a comprehensive and authori-
tativeworkof referenceonthesubjectof benzodiazepines
(BZDs). In his conclusions, Lader strongly recommends
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 invi-
tation to open a debate.
The first study of the efficacy of FLU-SI dates back to
lence and importance of BZD dependence. The clinical
the fingers of one hand . 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 princi-
pal activity of our Addiction Unit, involved in more than
then it has been used to treat more than 300 patients,
including many doctors, dependent on high doses of BZD
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
tapering takes. The crucial point is that these HDDs have
been the subject of very little study and are virtually
confined to patients with co-addictions and personality
of BZDs to create tolerance, along with their low toxicity,
can induce truly stupefying increments in dosage .
FLU-SI works best with HDD patients, but specialists
are not trying it: there have probably been too few scien-
the congress format, with a clearer emphasis on experi-
ence, 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
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 .
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 addic-
tion is the most typical form of iatrogenic dependence; or
is that the real reason for the lack of interest in it?
Declarations of interest
FABIO LUGOBONI1& ROBERTO LEONE2
Addiction Unit, Department of Internal Medicine,
Verona University Hospital, 37134 Verona,
Italy1and Pharmacological Unit, Department of
Public Health and Community Medicine,
Verona University Hospital, Verona, Italy2.
1. Lader M. Benzodiazepines revisited—will we ever learn?
Addiction 2011; 106: 2086–109.
2. Lugoboni F., Faccini M., Quaglio G. L., Albiero A., Pajusco B.
Intravenous flumazenil infusion to treat benzodiazepine
dependence should be performed in the inpatient clinical
setting for high risk of seizure. J Psychopharmacol 2011; 26:
3. Quaglio G. L., Lugoboni F., Fornasiero A., Lechi A., Gerra G.,
Mezzelani P. Dependance on zolpidem: two case reports of
detoxification with flumazenil infusion. Int Clin Psychophar-
macol 2005; 20: 285–7.
4. Hood S., O’Neil G., Hulse G. The role of flumazenil in the
treatment of benzodiazepine dependence: physiological and
psychological profiles. J Psychopharmacol 2009; 23: 401–9.
et al. Focal nonconvulsive seizures during detoxification for
benzodiazepine abuse. Epilepsy Behav 2011; 23: 168–70.
Addiction © 2012 Society for the Study of Addiction