Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings

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 individuals.

To evaluate the effectiveness of pharmacological interventions for benzodiazepine mono-dependence.

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.

Randomized trials of benzodiazepines dependence management regardless of type, dose (daily and total) and duration of benzodiazepine treatment.

Reviewers independently assessed trials for inclusion, rated their methodological quality and extracted data.

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).

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 modulator).