BehaveNet® Opinion
Does Flumazenil Contribute to Treatment for Alcohol Dependence?
Raymond Anton, MD, et al presented a poster*
at a recent meeting of the Research Society on Alcoholism describing a
placebo
controlled, randomized study of
flumazenil/hydroxyzine/gabapentin for
alcohol
dependence. Available as the Prometa protocol, this
off label use of off patent
drugs has been touted as a treatment for
alcoholism and
addictions to
methamphetamine and
cocaine.
In this study the flumazenil, a
benzodiazepine
antagonist,
was administered intravenously on two consecutive days. Hydroxyzine, an
antihistamine, was administered before the flumazenil infusions and at bedtime
as needed for six days. Participants, including some with "mild/moderate
alcohol withdrawal,"
took increasing doses of gabapentin for 39 days and attended counseling. Whether
the protocol in this study “cured” any of the subjects of alcoholism has
apparently not yet been determined. That might presumably take many years and
begs the question of whether this cure would simply
consist of successful abstinence or actual ability to drink “normally.” Participants
were reported to tolerate intravenous administration of flumazenil.
The other question that remains is whether the flumazenil (or the hydroxyzine)
adds anything to the effectiveness of gabapentin alone. Gabapentin, an
unscheduled
anticonvulsant drug also used off label to treat
anxiety, is an
obvious candidate for treating alcohol withdrawal. Flumazenil on the other hand
can precipitate seizures (at least in some patients who have recently used
benzodiazepines or other
sedative-hypnotics), something for which
alcoholics in withdrawal are
already at increased risk. We need a study comparing
flumazenil/hydroxyzine/gabapentin to gabapentin alone as well as to placebo to
settle that question. In the meantime, if you are thinking of trying this
combination on your patients, be warned that the protocol is protected by a
“use” patent (7,348,321) owned by Hythiam, Inc. If this corporation is looking
after its licensees and their considerable financial investment in the license,
Hythiam might sue you for patent infringement. But if the gabapentin works just
as well by itself, Hythiam might not have much worth licensing.
*R.F. Anton, H. Myrick, P. Latham, A. Baros, T. Wright, S. Stewart, R. Malcolm,
R. Wald, P. Randall “Double Blind Controlled Trial of Flumazenil and Gabapentin
for the Treatment of Alcohol Dependence”
July 22, 2008
-the editor
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