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All of these articles are available through Medline -  If you run a search on Benzodiazepine Withdrawal, you will come up with many more: 

Lack of cognitive recovery following withdrawal from long-term benzodiazepine use.

The prolonged benzodiazepine withdrawal syndrome: anxiety or hysteria

Protracted withdrawal syndromes from benzodiazepines.

Cognitive impairment in long-term benzodiazepine users.

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers.

Biological processes in benzodiazepine dependence.

Withdrawal phenomena after long-term administration of benzodiazepines. A review of recent investigations.

Motor phenomena in benzodiazepine withdrawal.

Title: Lack of cognitive recovery following withdrawal from long-term benzodiazepine use.

Author: Tata PR; Rollings J; Collins M; Pickering A; Jacobson RR

Address: Department of Psychology, St George's Hospital Medical School, University of London.

Source: Psychol Med, 24(1):203-13 1994 Feb


Twenty-one patients with significant long-term therapeutic benzodiazepine (BZ) use, who remained abstinent at 6 months follow-up after successfully completing a standardized inpatient BZ withdrawal regime, and 21 normal controls matched for age and IQ but not for anxiety, were repeatedly tested on a simple battery of routine psychometric tests of cognitive function, pre- and post-withdrawal and at 6 months follow-up. The results demonstrated significant impairment in patients in verbal learning and memory, psychomotor, visuo-motor and visuo-conceptual abilities, compared with controls, at all three time points. Despite practice effects, no evidence of immediate recovery of cognitive function following BZ withdrawal was found. Modest recovery of certain deficits emerged at 6 months follow-up in the BZ group, but this remained significantly below the equivalent control performance. The implications of persisting cognitive deficits after withdrawal from long-term BZ use are discussed. 

Title: The prolonged benzodiazepine withdrawal syndrome: anxiety or hysteria?

Author: Higgitt A; Fonagy P; Toone B; Shine P

Address: St Charles Hospital, London, United Kingdom.

Source:  Acta Psychiatr Scand, 82(2):165-8 1990 Aug


In an attempt to establish whether prolonged withdrawal symptoms after stopping intake of benzodiazepines is caused by return of anxiety, hysteria, abnormal illness behaviour or the dependence process itself producing perhaps a prolonged neurotransmitter imbalance, a group of such patients suffering prolonged withdrawal symptoms (PWS) was compared on a range of psychophysiological measures with matched groups of anxious and conversion hysteria patients and normal controls. It was found that the psychophysiological markers of anxiety were not marked in the PWS group; nor were the averaged evoked response abnormalities found to be associated with cases of hysterical conversion in evidence. The PWS group were hard to distinguish from normal controls on the basis of psychophysiological measures and thus it was felt to be unlikely to be an affective disturbance. It was concluded that PWS is likely to be a genuine iatrogenic condition, a complication of long-term benzodiazepine treatment. 

Title: Protracted withdrawal syndromes from benzodiazepines.

Author: Ashton H

Address: Department of Pharmacological Sciences, The University, Newcastle upon Tyne, England.

Source: J Subst Abuse Treat, 8(1-2):19-28 1991


The benzodiazepine withdrawal syndrome is a complex phenomenon which presents serious difficulties in definition and measurement. It is particularly difficult to set out precise limits on its duration. Many withdrawal symptoms are a result of pharmacodynamic tolerance to benzodiazepines, some mechanisms for which are discussed. Such tolerance develops unevenly in different brain systems and may be slow to reverse. Withdrawal symptoms occurring in the first week after cessation of drug use tend to merge with more persistent symptoms that may last for many months. These prolonged symptoms do not necessarily constitute "true pharmacological withdrawal symptoms, but are nevertheless related to long-term benzodiazepine use. Such symptoms can include anxiety, which may partly result from a learning deficit imposed by the drugs, and a variety of sensory and motor neurological symptoms. The protracted nature of some of these symptoms raises the possibility that benzodiazepines can give rise not only to slowly reversible functional changes in the central nervous system, but may also occasionally cause structural neuronal damage. 

Title: Cognitive impairment in long-term benzodiazepine users.

Author: Golombok S; Moodley P; Lader M

Address: Institute of Psychiatry, London.

Source: Psychol Med, 18(2):365-74 1988 May


In view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in long-term benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function. 

Title:  Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers.

Author: Schmauss C; Krieg JC

Address:   Max-Planck-Institute for Psychiatry, Munich, FRG.

Source:  Psychol Med, ():


In 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high- and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

Title: Biological processes in benzodiazepine dependence.

Author:  Lader M

Address: Institute of Psychiatry, London, UK.

Source:  Addiction, 89(11):1413-8 1994 Nov


The indications for the benzodiazepines include anxiety, insomnia, muscle spasm and epilepsy and each disorder has a variety of biological substrates. Limbic structures and the neurotransmitters noradrenaline, 5-HT and GABA have all been implicated. Benzodiazepines act on allosteric receptor sites and potentiate the actions of GABA in modulating chloride ionophores across nerve membranes. These effects can be blocked by the benzodiazepine antagonist, flumazenil. The molecular pharmacology of the benzodiazepine-GABA-chloride receptor is complex, with a wide range of different subunits. Animal models of dependence have suggested that the changes associated with long-term benzodiazepine use are related more to receptor-effector coupling than to the receptor characteristics themselves. Thus, benzodiazepine agonists on long-term use lose their efficacy, antagonists become partial inverse antagonists, and inverse agonists increase in efficacy. Various clinical implications are explored, including the use of flumazenil to prevent and to treat benzodiazepine withdrawal syndromes.

Title: Withdrawal phenomena after long-term administration of benzodiazepines. A review of recent investigations.

Author:  Sch¨opf J

Source: Pharmacopsychiatria, 16(1):1-8 1983 Jan


Recent studies report the occurrence of withdrawal reactions in a significant number of patients after long-term use of benzodiazepines, i.e. daily use for one year or more. The abstinence syndrome is partially characterized by anxiety, dysphoria, sleep disturbances and other unspecific symptoms. In addition, some patients experience symptoms, which, so far, have not been described as typical part of a withdrawal syndrome, especially disturbances of sensory perception. The withdrawal syndrome is less acutely distressing than a classical withdrawal syndrome of the barbiturate type, but occasionally it can show a protracted course. 

Title: Motor phenomena in benzodiazepine withdrawal.

Author: Rapport DJ; Covington EC

Address:  Cleveland Clinic Foundation, Ohio.

Source:  Hosp Community Psychiatry, 40(12):1277-9 1989 Dec


Chronic use of benzodiazepines, the most widely prescribed of all psychotropic medicines, may lead to severe symptoms of withdrawal when the drugs are discontinued. The authors describe two cases of benzodiazepine withdrawal accompanied by unusual muscle activity. The neurologic mechanism for the motor abnormalities appears to be marked disinhibition of subcortical motor areas normally inhibited by gamma-aminobutyric acid. The motor phenomena may persist long after the more common signs of withdrawal have resolved and, if unrecognized, can lead to such misdiagnoses as drug seeking, conversion, hysteria, or malingering.


Disclaimer:  The information contained in this website was not compiled by a doctor or anyone with medical training. The advice contained herein should not be substituted for the advice of a physician who is well-informed in the subject matter discussed. Before making any decisions about your health or treatment you should always confer with your physician and it is always assumed that you will do so.

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Last updated 21 July 2020