Calcification of radiolucent gall stones during treatment with ursodeoxycholic acid.

645 Physiologically the electroencephalographic changes comprised pronounced reduction in fast-wave activity as the drugs were withdrawn. This drug-related effect is the reverse of the increase normally seen after administration of benzodiazepines.1 We have also observed that auditory-evoked responses to clicks increase from very small prewithdrawal values to normal values over the same time. These effects may reflect psychological variables such as attention and arousal, and could be regarded as objective indicators of the hypersensitivity reported by many patients. Psychological performance improved with time, as shown by the Digit Symbol Substitution Test. This test is subject to some effect of practice but not usually beyond two or three occasions. Furthermore, the improvement was too large to be explained by this alone. More likely it implies psychological impairment during chronic benzodiazepine ingestion, which suggests that such chronic usage has its drawbacks. Other reports have generally suggested little concern,'2 but most were on patients who had escalated their dosage. Our findings, like those of other recent reports,9 13 14 show that patients taking benzodiazepines in therapeutic doses risk developing some form of dependence.'5 We emphasise, however, that our patients were long-term uscrs of benzodiazepines and were self-selected, in that they were referred because of their inability to stop their medication. Hence the present cohort may not be representative of benzodiazepine users generally, an issue which will be resolved only with proper epidemiological studies. Nevertheless, detecting withdrawal symptoms in patients taking normal therapeutic doses increases the urgency of the problem and argues against regular daily medication for chronic anxiety. Many thousands of patients may be at risk, as some 20' or so of the adult population take benzodiazepines chronically. We thank R Smokcum for benzodiazepine assay data; Berk Pharmaceuticals Ltd, Hoechst UK Ltd, and Wyeth Laboratories for providing benzodiazepines and matching placebos; and Drs T Christie, J Marks, and P Harris for helpful comments. References 'Balter MB, Levine J, Manheimer DI. Cross-national study of the extent of anti-anxiety/sedative drug use.