The long-term effects of benzodiazepines (BDZ) on psychomotor and cognitive functions were assessed in 28 out patients, users of low therapeutic doses of diazepam (13.6 ± 4.9 mg/day, range: 5-20 mg/day) for 5-20 years (10.1 ± 5.0 years). These patients' performance was compared with two control groups: 53 BDZ-free anxious out patients and 56 healthy volunteers. The three groups were similar in sex, age and education. BDZ chronic users were tested before and after short-term (3 weeks) and long-term discontinuation (at an average of 10 months). Performance of chronic users of BDZ was consistently worse than those of the control groups, suggesting an impairment in these patients on both psychomotor and cognitive functions. These were not related to either dose or cumulative exposure to BDZ, and were also independent of diagnosis and levels of anxiety and depression. Moreover, these deficits were persistent as their performance failed to improve after drug discontinuation.
American Psychiatric Association (1990) Benzodiazepine dependence, toxicity, and abuse. A task force report of the American Psychiatric Association. American Psychiatric Press, Washington, DC
2.
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, Revised. American Psychiatric, Washington, DC
3.
Ballenger J.C., Burrows G.D., DuPont R.L. Jr, Lesser I.M., Noyes R. Jr, Pecknold J.C., Rifkin A., Swinson R.P. (1988) Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. Arch Gen Psychiatr45: 413-422
4.
Beck A.T., Steer R.A., Garbin M.G. (1988) Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev8: 77-100
5.
Beck A.T., Ward C., Mendelson M., Mock J., Erbaugh J. (1961) An inventory for measuring depression. Arch Gen Psychiatr4: 561-571
6.
Bergman H., Borg S., Holm L. ( 1980) Neuropsychological impairment and exclusive abuse of sedatives or hypnotics. Am J Psychiatr137: 215-217
7.
Biaggio A M B, Natalicio L. (1979) Manual para o inventário de ansiedade traço-estado (IDATE). Centro Editor de Psicologia Aplicada-CEPA, Rio de Janeiro, Brazil
8.
Bond A.J., Lader M.H. (1972) Residual effects of hypnotics. Psychopharmacologia25:17-32
9.
deGier J.J., Hart B.J., Nelemans F.A., Bergman H. (1981) Psychomotor performance and real driving performance of outpatients receiving diazepam. Psychopharmacology73: 340-344
10.
Golombok S., Moodley P., Lader M. (1988) Cognitive impairment in long-term benzodiazepine users. Psychol Med18: 365-374
11.
Gorenstein C., Tavares S.M., Gentil V., Peres C., Moreno R.A., Dreyfus J.F. (1990) Psychophysiological effects and dose equivalence of zopiclone and triazolam administered to healthy volunteers. Methodological considerations. Braz J Med Biol Res23: 941-951
12.
Gorenstein C., Bernik M.A., Pompéia S. (1994) Differential acute psychomotor and cognitive effects of diazepam on long-term benzodiazepine users. Int Clin Psychopharmacol9: 145-153
13.
Hamilton M. (1960) A rating scale for depression. J Neurol Neurosurg Psychiatr23: 56-62
14.
Hendler N., Cimini C., Terence M.A., Long D. ( 1980) A comparison of cognitive impairment due to benzodiazepines and narcotics. Am J Psychiatr137: 828-830
15.
Hollister L.E., Müller-Oerlinghausen B., Rickels K., Shader R.I. (1993) Clinical uses of benzodiazepines. J Clin Psychopharmacol13:1S-169S
16.
Kapur N. (1988) Memory disorders in clinical practice. Butterworths and Co., London
17.
Koelega H.S. (1989) Benzodiazepines and vigilance performance: a review . Psychopharmacology98: 145-156
18.
Lader M.H., Ron M., Petursson H. (1984) Computer axial brain tomography in long-term benzodiazepine users. Psychol Med14: 203-206
19.
Lister R.G. (1985) The amnesic action of benzodiazepines in man. Neurosci Behav Rev9: 87-94
20.
Lucki I., Rickels K., Geller A.M. (1986) Chronic use of benzodiazepines and psychomotor and cognitive test performance. Psychopharmacology88: 426-433
21.
Marcourakis T., Gorenstein C., Gentil V. (1993) Clomipramine, a better reference drug for panic/agoraphobia. II. Psychomotor and cognitive effects. J Psychopharmacol7:325-330
22.
Moodley P., Golombok S., Shine P., Lader M. (1993) Computed axial brain tomograms in long-term benzodiazepine users. Psychiatr Res48:135-144
23.
Oster G., Huse D.M., Adams S.F., Imbimbo J., Russell M.W. (1990) Benzodiazepine tranquilizers and the risk of accidental injury. Am J Public Health80:1467-1470
24.
Paykel E.S. (1987) Depression, anxiety and antidepressant response . In Racagni G, Smeraldi E (eds), Anxious depression: assessment and treatment . Raven Press, New York, pp.171-180
25.
Peat M.A., Kopjak L. (1979) The screening and quantitation of diazepam, flurazepam, chlordiazepoxide, and their metabolites in blood and plasma by electron-capture gas chromatography and high pressure liquid chromatography. J Forensic Sci24: 46-54
26.
Petursson H., Lader M. (1984) Dependence on tranquilizers. Maudsley Monograph 28. Oxford University Press, Oxford
27.
Petursson H., Gudjonsson G.H., Lader M.H. (1983) Psychometric performance during withdrawal from long-term benzodiazepine treatment. Psychopharmacology81: 345-349
28.
Schmauss C., Krieg J.C. (1987) Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers. Psychol Med17: 869-873
29.
Silverstone T., Turner P. (1974) Drug treatment in psychiatry. Routledge and Kogan Paul, London
30.
Spielberger C.D., Gorsuch R.L., Lushene R.E. (1970) Manual for the State-Trait anxiety inventory. Consulting Psychologists Press, Palo Alto, CA
31.
Spitzer R.L., Endicott J. (1979) Schedule for affective disorders and schizophrenia-life time version (SADS-L), 3rd edn. New York State Psychiatric Institute, New York
32.
Stewart S.H., Pihl R.O., Padjen A.L. (1992) Chronic use of alcohol and/or benzodiazepines may account for evidence of altered benzodiazepine receptor sensitivity in panic disorder. Arch Gen Psychiatr49: 329-330
33.
Tata P.R., Rollings J., Collins M., Pickering A., Jacobson R.R. (1994) Lack of cognitive recovery following withdrawal from long-term benzodiazepine use. Psychol Med24: 203-213
34.
Wechsler D.A. (1955) Manual for the Wechsler adult intelligence scale . National Foundation for Educational Research, London
35.
Wechsler D.A. (1945) A standardized memory scale for clinical use. J Psychol19: 87-95
36.
Wittchen H.U. (1986) Epidemiology of panic attacks and panic disorders . In Hand I, Wittchen H U (eds), Panic and phobias: empirical evidence of theoretical models and long-term effects of behavioral treatments. Springer-Verlag, Berlin
37.
Woods J.H., Katz J.L., Winger G. (1987) Abuse liability of benzodiazepines. Pharmacol Rev39: 251-413
