Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings.
Cochrane Database of Systematic Reviews. 2006-07-19; :
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Denis C(1), Fatséas M, Lavie E, Auriacombe M.
(1)Universite Victor Segalen Bordeaux – Centre Carreire du CHCP, Laboratoire de
Psychiatrie, 121 rue de la Bechade, Bordeaux Cedex, European Union 33076.
Cochrane Database Syst Rev. 2013;6:CD005194.
BACKGROUND: The improved safety profile of benzodiazepines compared to
barbiturates has contributed to a high rate of prescription since the seventies.
Although benzodiazepines are highly effective for some disorders, they are
potentially addictive drugs and they can provide reinforcement in some
OBJECTIVES: To evaluate the effectiveness of pharmacological interventions for
SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group’ Register of
Trials (October 2004), the Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (January 1966 to October
2004), EMBASE (January 1988 to October 2004), PsycInfo (1985 to October 2004),
CINAHL (1982 to October 2004), Pascal, Toxibase, reference lists of articles.
SELECTION CRITERIA: Randomized trials of benzodiazepines dependence management
regardless of type, dose (daily and total) and duration of benzodiazepine
DATA COLLECTION AND ANALYSIS: Reviewers independently assessed trials for
inclusion, rated their methodological quality and extracted data.
MAIN RESULTS: Eight trials involving 458 participants were included. The studies
included could not be analysed cumulatively because of heterogeneity of
inteventions and participants’ characteristics. Results support the policy of
gradual rather than abrupt withdrawal of benzodiazepine. Progressive withdrawal
(over 10 weeks) appeared preferable if compared to abrupt since the number of
drop-outs was less important and the procedure judged more favourable by the
participants. Short half-life benzodiazepine, associated with higher drop-out
rates, did not have higher withdrawal symptoms scores. Switching from short
half-life benzodiazepine to long half-life benzodiazepine before gradual taper
withdrawal did not receive much support from this review. The role of propanolol
in benzodiazepine withdrawal was unclear; adding tricyclic antidepressant
(dothiepin) decreased the intensity of withdrawal symptoms but did not increase
the rate of benzodiazepine abstinence at the end of the trial. Buspirone and
Progesterone failed to suppress any benzodiazepine symptoms. Carbamazepine might
have promise as an adjunctive medication for benzodiazepine withdrawal,
particularly in patients receiving benzodiazepines in daily dosages of 20 mg/d or
more of diazepam (or equivalents).
AUTHORS’ CONCLUSIONS: The results of this systematic review point to the
potential value of carbamazepine as an effective intervention for benzodiazepine
gradual taper discontinuation. Carbamazepine has shown rather modest benefit in
reducing withdrawal severity, although it did significantly improve drug-free
outcome. Larger controlled studies are needed to confirm these benefits, to
assess adverse effects and to identify when its clinical use might be most
indicated. Other suggested treatment approaches to benzodiazepine discontinuation
management should be explored (antidepressants, benzodiazepine receptors