Physical dependence on benzodiazepines: differences within the class.

Concern about physical dependence seems to be the major limiting factor in the long-term treatment with benzodiazepines (BZD). The severity of the withdrawal syndrome is determined by multiple factors, e.g. dose, duration of use, frequency of dose interval, mode of discontinuation, the pharmacologic characteristics of the BZD, personality and previous or concurrent use of cross-dependent drugs and/or alcohol. There is evidence that BZD with a short elimination half-life cause a more severe withdrawal syndrome than those with a long elimination half-life. Besides pharmacokinetic properties, pharmacodynamic factors such as potency may also covary with the liability of a BZD to induce physical dependence. There is an increasing body of literature indicating that quickly eliminated, high potency BZD such as alprazolam and lorazepam may be more likely to cause severe withdrawal reactions than slowly eliminated compounds such as diazepam or less potent derivatives such as oxazepam. Alprazolam seems to play an exceptional role, insofar as relatively soon after its introduction to the market a number of case reports of withdrawal psychoses, seizures and intense rebound anxiety were published. Data reviewed from the literature correspond well with the results of interviews conducted with 31 clinicians across the United States with experience in detoxifying patients dependent on BZD, 84% of these physicians mentioning alprazolam as especially problematic with respect to the intensity and/or duration of the withdrawal syndrome.