Benzodiazepine dependence. A review of the evidence

Classical pharmacological dependence accompanied by euphoria, clinical evidence of tolerance and escalation of dosage are very rare with the benzodiazepines. However, there is now abundant evidence that prolonged administration of doses within the therapeutic range leads to true dependence in a significant minority of patients. This dependence is characterised by withdrawal symptoms on stopping treatment; these include perceptual disturbances, epileptic seizures, weight loss, insomnia and autonomic symptoms. As some of the symptoms are qualitatively different from those of anxiety neurosis, and as the withdrawal syndrome commonly lasts between 5 and 15 days, the possibility that the symptoms represent a return of pre-existing anxiety can be discounted. The withdrawal syndrome is more likely if: (a) the benzodiazepine has been taken in regular dosage for more than 4 months; (b) higher dosages have been used; (c) the drug is stopped suddenly; and (d) a short acting benzodiazepine has been taken. The withdrawal syndrome is most likely to occur when there is a rapid fall in blood benzodiazepine concentrations; this may be associated with altered sensitivity of benzodiazepine receptors. The syndrome can best be avoided by gradual reduction of dosage. The temporary prescription of other drugs, particularly beta-adrenoceptor blocking drugs, may attenuate withdrawal symptoms, but antipsychotic drugs in low dosage are of no benefit.