BENZODIAZEPINES
Quotations & Abstracts
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. [SUMMARY p. 203]
"The main cognitive functions *****sed in this study include working
memory,
verbal learning and memory, visuo-motor and visuo-conceptual skills. The
lack of evidence for clinically significant cognitive recovery raises
concern about the severity and reversibility of any underlying BZ-induced
organic impairment." [p. 211]
"The adverse effects of acute diazepam administration on memory and
arousal
in man are well known (Lister & File, 1984; Lister, 1985), and have been
linked to the high density of BZ receptors in the hippocampus and
reticular
formation (Wolkowitz et al. 1987), although the neurochemical basis of
chronic post-withdrawal deficits has yet to be demonstrated." [p. 212]
"Persisting neuropsychological deficits affecting psychomotor function and
new verbal learning have occupational implications. Driving and safety at
work with machinery may both be impaired (Skegg et al. 1979, Roy-Byrne &
Cowley, 1990).Patients' impairment, following withdrawal from long-term
BDZ
use, is likely to be less than that due to acute drug ingestion or the
early
withdrawal phase. Yet, one must be cautious in predicting either rapid or
comprehensive cognitive recovery for those patients contemplating or
undergoing a withdrawal regime, or in estimating the cognitive effects of
mood dysfunction, which require further investigation." [p. 211] Lack of
Cognitive Recovery Following Withdrawal from Long-Term Benzodiazepine Use.
Tata PR, Rollings J, Collins M, Pickering A, Jacobson RR, Psychological
Medicine 1994; 24: 203-213.
"...the use of benzodiazepines in patients with chronic pain would
theoretically be ill-advised because they reduce the turnover of
s*****onin,
thus interfering with natural sleep and lowering the tolerance to chronic
pain. However, the most significant problem that benzodiazepines create
seems to be cognitive impairment with associated EEG changes (--). Acute,
single dose administration of diazepam does seem to produce impairment in
learning, memory, and psychomotor functioning." [p. 828]
"...the evaluating psychiatrist noted that a great deal of cognitive
impairment seemed to occur more often in patients using benzodiazepines
than
in patients using only narcotics." [p. 828]
"...one could conclusively state that benzodiazepines were far more likely
to produce cognitive impairment, with concomitant EEG changes, than were
narcotics."[p. 830] " While neither narcotics nor benzodiazepines should
be
used on a long-term basis, cognitive impairment was far more apparent with
the latter class of drugs. The question of the reversibility of the
benzodiazepine effect is the subject of current research, but at this time
one may only underscore a recent suggestion by the Food and Drug
Administration that benzodiazepines be limited to short-term use." [p.
830]
Comparison of Cognitive Impairment Due to Benzodiazepines and to
Narcotics.
American Journal of Psychiatry 1980; 137: 828-830.
"The committee further noted that there was little convincing evidence
that
benzodiazepines were efficacious in the treatment of anxiety after four
months' continuous treatment. It considered that an appropriate warning
regarding long-term efficacy be included in the recommendations,
particularly in view of the high pro****tion of patients receiving repeated
prescriptions for extended periods of time ... It further suggested that
patients receiving benzodiazepine therapy be carefully selected and
monitored and that prescriptions be limited to short-term use" Committee
on
Review of Medicines, Systematic Review of the Benzodiazepines, Brit Med J,
29 March 1980, 910-912.
"Benzodiazepine dependence would be of minor clinical significance if it
occurred only in those few individuals taking high doses of drugs; but it
would be very im****tant indeed if it supervened even to a minor degree in
patients on usual clinical doses. Our clinical impression is that many
patients experience symptoms on reduction or withdrawal of their
benzodiazepine medication, and that whilst these symptoms somewhat
resemble
those of anxiety they differ qualitatively and are often more severe than
those for which the medication was originally given" C. Hallström, M.
Lader,
Benzodiazepine withdrawal phenomena, Int. Pharmacopsychiat, 1981, 16,
235-244.
"Dependence on the benzodiazepines does occur. Patients taking these
drugs,
even at therapeutic doses, for two or more months, may develop a physical
withdrawal syndrome. The cardinal feature of the syndrome is anxiety,
which
may be mistakenly interpreted as a recrudescence of the original anxiety
for
which the drug was prescribed" N. Hockings, B.R. Ballinger, Hypnotics and
anxiolytics, in New Drugs, [London: British Medical Association, 1983,
149-155.
"The medical profession took nearly 20 years from the introduction of
benzodiazepines to recognise officially that these minor tranquillisers
and
hypnotics were potentially addictive. The 'happiness pills', which had
been
propping up a fair pro****tion of the adult population since the early
1960s,
were found to have an unexpectedly bitter aftertaste: doctors and patients
alike were unprepared for the problems of dependence and withdrawal that
are
now known to be common even with normal therapeutic doses" Editorial
(Anon),
The benzodiazepine bind, The Lancet, 22 September 1984, 706.
"The extent of pharmacological dependence with regular as opposed to
intermittent dosage of benzodiazepines was not fully appreciated until
recently. This was probably because prominent features of drug dependence,
such as tolerance and escalation of dosage, are uncommon among patients
starting on normal doses. The chief manifestation is a withdrawal syndrome
on stopping the drug" Anon (A. Herxheimer, ed.), Some problems with
benzodiazepines, Drug & Ther Bull, March 25 1985, 23 (6), 21-23.
"In the UK, 11.2% of all adults take an anti-anxiety drug at some time
during any one year. But over a quarter of these people (3.1% of all
adults)
are chronic users, taking such medication every day. Even at a
conservative
estimate, 20% of these will develop symptoms when they attempt to
withdraw.
That means a quarter of a million people in the UK. The sooner the medical
profession faces up to its responsibilities towards these iatrogenic
addicts, the sooner it will regain the confidence of the anxious members
of
our community" M.H. Lader, A.C. Higgitt, Management of benzodiazepine
dependence - Update 1986, Brit J Addiction, 1986, 81, 7-10.
"There is now little doubt that regular use of benzodiazepines can lead to
drug dependence in patients who are not drug abusers. Such patients come
to
rely on the drugs for psychological comfort and suffer withdrawal symptoms
if the drug is stopped or the dosage reduced. It is estimated that
one-third
of patients taking benzodiazepines for six months become dependent...
Present estimates suggest that perhaps 500,000 people in the UK... are now
dependent on benzodiazepines" H. Ashton, Dangers and medico-legal aspects
of
benzodiazepines, J. Med Defence Union, Summer 1987, 6-8.
"It seems likely that many popular beliefs about benzodiazepine
'addiction'
are related to the clear cut and increasingly do***ented phenomenon of
withdrawal reactions following the use of these drugs and to the resulting
difficulty anxious patients sometimes have stopping drug treatment because
of such reactions. This phenomenon (ie inability to discontinue the drug
because of withdrawal symptoms) is termed 'dependence' and by itself is
enough to qualify patients for the new DSM-III-R. Diagnostic and
Statistical
Manual of Mental Disorders, 3rd ed., revised) diagnosis of 'psychoactive
substance dependence" (P.R. Roy-Byrne, D. Homer, Benzodiazepine
withdrawal:
overview and implications for the treatment of anxiety, Am J Med, June
1988,
84, 1041 - 1052.
"It has been estimated that one in three patients prescribed
benzodiazepines
in normal therapeutic doses for six weeks would experience withdrawal
symptoms if treatment were withdrawn abruptly. Even with gradual
withdrawal,
patients would request further prescriptions. Thus, there is a
considerable
risk of dependence even in comparatively short-term use" M.A. Cormack,
R.G.
Owens, M.E. Dewey, The effect of minimal interventions by general
practitioners on long-term benzodiazepines use, J Roy Coll Gen
Practitioners, October 1989, 39, 408-411.
"The presence of a predictable abstinence syndrome following abrupt
discontinuance of benzodiazepines is evidence of the development of
physiological dependence... "Historically, long-term, high-dose,
physiological dependence has been called addiction, a term that implies
recreational use. In recent years, however, it has become apparent that
physiological adaptation develops and discontinuance symptoms can appear
after regular daily therapeutic dose administration ... in some cases
after
a few days or weeks of administration. Since therapeutic prescribing is
clearly not recreational abuse, the term dependence is preferred to
addiction, and the abstinence syndrome is called a discontinuance
syndrome"
American Psychiatric Association Task Force on Benzodiazepine Dependency.
Benzodiazepine Dependence, Toxicity, and Abuse. Wa****ngton DC: APA, 1990.
"I don't think anyone really knows what long-term effects the
benzodiazepines are likely to have on the brain tissue ... [they] may
damage
your brain cells and produce real physical damage to your thinking
processes
and there is also the risk that the benzodiazepines will cause
psychological
damage." Dr Vernon Coleman, Life Without Tranquillisers, 1985, p55.
Drug companies making these products constantly warn doctors not to allow
patients to take them for more than a week or two. They advise doctors not
to make these drugs available on 'repeat prescription'. Evidence showing
that these drugs are addictive and potentially dangerous has been
ac***ulating rapidly since the early 1970s. Numerous research papers have
been published showing that products in this group can cause problems such
as memory loss as well as anxiety, depression and sleeplessness.
Ironically, these are the three symptoms for which they are most commonly
prescribed. The Committee on Safety of Medicines has received re****ts
showing that these drugs are well known to cause well over 100 different
side effects. Earlier this month the DHSS and the Home Office publicly
admitted that the size of Britain's tranquilliser addiction problem is
worrying them by bringing these drugs under the Misuse of Drugs Act 1971 -
the same legislation that controls drugs such as heroin. And yet thousands
of doctors don't seem to take any notice. It may be true that many still
don't know what else to do for patients who are suffering from anxiety or
stress-related diseases. The only conclusion I can draw is that several
thousand British doctors do not read articles in the medical journals nor
do
they study literature which is published by the drug companies.
These painfully ignorant doctors have between them created the biggest
drug
addiction problem this country has ever known. It's their addiction to
prescribing these terrible drugs that has given us a nation of junkies.
The
nightmare pills: How millions are caught in the tranquilliser trap, Today,
07 May, 1986, Dr Vernon Coleman.
"Anxiolytic treatment should be limited to short periods... because of the
danger of insidious development of dependence and subsequent difficulty in
withdrawing the drug... Withdrawal of the drug following either high
dosage
or long-term administration should be gradual as abrupt withdrawal may
produce confusion, toxic psychosis, convulsions or a condition resembling
delirium tremens. In milder cases symptoms may be similar to the original
complaint and encourage further prescribing." 1981 British National
Formulary.
Anxiolytic treatment should be limited to the lowest possible dose for the
shortest possible time... Prescribing of these drugs is widespread but
dependence (both physical and psychological) and tolerance occurs. This
may
lead to difficulty in withdrawing the drug after the patient has been
taking
it regularly for more than a few weeks. Hypnotics and anxiolytics should
therefore be reserved for short courses to alleviate acute conditions.
British National Formulary, March 1998 edition.
Benzodiazepines are indicated for the short-term relief (two to four weeks
only) of anxiety that is severe, disabling or subjecting the individual to
unacceptable distress, occurring alone or in association with insomnia or
short-term psychosomatic, organic or psychotic illness. The use of
benzodiazepines to treat short-term 'mild' anxiety is inappropriate and
unsuitable. Benzodiazepines should be used to treat insomnia only when it
is
severe, disabling, or subjecting the individual to extreme distress. The
Committee on Safety of Medicines, January 1988.
"Prolonged or excessive use of benzodiazepines may occasionally result in
the development of psychological dependence with withdrawal symptoms on
sudden discontinuation. This is more likely in patients with a history of
alcoholism, drug abuse or patients with marked personality disorders.
Treatment in all patients should be withdrawn gradually. Careful
monitoring
of all patients is essential." 1983 John Wyeth Data Sheet.
"It is more difficult to withdraw people from BDZs than it is heroin, it
just seems that the dependency is so ingrained and the withdrawal symptoms
you get are so intolerable that people have a great deal of problem coming
off. The other aspect is that with heroin, usually the withdrawal is over
within a week or so, with BDZs, a pro****tion of patients go on to long
term
withdrawal & they have very unpleasant symptoms for month after month, & I
get letters from people saying you can go on for two years or more. Some
of
the tranquilliser groups can do***ent people who still have symptoms ten
years after stopping." Professor Malcolm H Lader, Royal Maudesley
Hospital,
"You & Yours" - BBC Radio 4, 1999.
The benzodiazepines are still extensively used in psychiatry, neurology
and
medicine in general. Anxiety disorder and severe insomnia are im****tant
syndromal indications, but these drugs are widely prescribed at the
symptomatic level, resulting in potential overuse. The official data
sheets
recommend short durations of usage and conservative dosage. Although
short-term efficacy is established, long-term efficacy remains
controversial, as relevant data are scanty and relapse, rebound and
dependence on withdrawal not clearly distinguished. The risks of the
benzodiazepines are well-do***ented and comprise psychological and
physical
effects. Among the former are subjective sedation, paradoxical release of
anxiety and/or hostility, psychomotor impairment, memory disruption, and
risks of accidents. Physical effects include vertigo, dysarthria, ataxia
with falls, especially in the elderly. Dependence can supervene on
long-term
use, occasionally with dose escalation. The benzodiazepines are now
recognised as major drugs of abuse and addiction. Other drug and non-drug
therapies are available and have a superior risk benefit ratio in
long-term
use. It is concluded that benzodiazepines should be reserved for
short-term
use - up to 4 weeks - and in conservative dosage. Professor Malcolm H
Lader,
Institute of Psychiatry, University of London, UK. Limitations on the use
of
benzodiazepines in anxiety and insomnia: are they justified? In: Eur
Neuropsychopharmacol 1999 Dec;9 Suppl 6:S399-405.
The concepts of dependence, addiction and abuse comprise overlapping
clinical phenomena. The earlier anxiolytic drugs, in particular the
barbiturates, were prone to abuse, i.e., non-medical use, and to high-dose
misuse. Their modern counterparts, the benzodiazepines, are abused in a
patchy way and are sometimes taken in regularly high doses. However, the
main problem is physical dependence as manifested by a withdrawal syndrome
on discontinuation of the drug. The withdrawal syndrome has been carefully
described and comprises physical and psychological features. In
particular,
perceptual symptoms such as photophobia, hyperacusis and feelings of
unsteadiness may predominate. The syndrome may come on during dosage
reduction but generally starts 2-10 days after cessation of the
benzodiazepine, depending on its elimination half-life. About a third of
long-term users suffer a recognisable syndrome even after a tapered
withdrawal, its duration usually being only a few weeks. A few patients go
on to a prolonged withdrawal syndrome, often characterised by muscular
spasm. The treatment of the withdrawal syndrome is sup****tive and
non-specific. A few patients started on benzodiazepine therapy escalate
the
dose. They tend to show the characteristic 'passive-dependent' personality
features and may previously have misused other CNS depressants such as the
barbiturates and alcohol. Abuse of benzodiazepines occurs in a rather
varied
way from country to country. Worldwide, flunitrazepam has caused concern
but, in the UK, the main problem has been the intravenous use of
temazepam.
The molecular pharmacology of the benzodiazepine receptor has been
extensively studied and is undoubtedly complex. Professor Malcolm H Lader,
Department of Clinical Psychopharmacology, Institute of Psychiatry,
London,
UK. Anxiolytic drugs: dependence, addiction and abuse. Eur
Neuropsychopharmacol 1994 Jun;4(2):85-91.
Withdrawal of benzodiazepines is currently advised for long-term
benzodiazepine users because of doubts about continued efficacy, risks of
adverse effects, including dependence and neuropsychological impairment
and
socio-economic costs. About half a million people in the UK may need
advice
on withdrawal. Successful withdrawal strategies should combine gradual
dosage reduction and psychological sup****t. The benzodiazepine dosage
should
be tapered at an individually titrated rate which should usually be under
the patient's control. The whole process may take weeks or months.
Withdrawal from diazepam is convenient because of available dosage
strengths, but can be carried out directly from other benzodiazepine.
Adjuvant medication may occasionally be required (antidepressants,
propranolol) but no drugs have been proved to be of general utility in
alleviating withdrawal-related symptoms. Psychological sup****t should be
available both during dosage reduction and for some months after cessation
of drug use. Such sup****t should include the provision of information
about
benzodiazepines, general encouragement, and measures to reduce anxiety and
promote the learning of non-pharmacological ways of coping with stress.
For
many patients the degree of sup****t required is minimal; a minority may
need
counselling or formal psychological therapy. Unwilling patients should not
be forced to withdraw. With these methods, success rates of withdrawal are
high and are unaffected by duration of usage, dosage or type of
benzodiazepine, rate of withdrawal, symptom severity, psychiatric history
or
personality disorder. Longer-term outcome is less clear; a considerable
pro****tion of patients may tem****arily take benzodiazepines again and some
need other psychotropic medication. However, the outcome may be improved
by
careful pharmacological and psychological handling of withdrawal and
post-withdrawal phases. Ashton CH, Department of Pharmacological Sciences,
University of Newcastle upon Tyne, UK. The treatment of benzodiazepine
dependence, Addiction 1994 Nov;89(11):1535-41.
This paper presents the results of a survey carried out to investigate the
benzodiazepine (BZD) prescribing patterns of the general practitioners
(GP)
in the catchment area of a Drug Dependence Unit located in a general
hospital in Mataro (Barcelona, Spain). The aims of the survey were: (i) to
obtain descriptive information on the knowledge of the GPs about BZD and
its
potential for dependence; (ii) to study the frequency of their
prescribing;
and (iii) to examine different factors linked to their prescribing. The
study was carried out using a combination of a personal interview and a
self-administered questionnaire. A total of 68 doctors (88.3%) completed
the
questionnaire. The results show that the GPs have, in general, correct
knowledge about the therapeutic indications for BZD prescribing, but are
far
less aware of their potential to induce dependence and how to manage
withdrawal. The rate of prescribing seems to be high. Furthermore, the
results of the external check of validity point out that doctors tend to
underestimate the number of prescriptions. The majority of GPs express the
need for alternative resources to BZD prescribing. No significant
associations have been found between doctor's characteristics, such as
postgraduate training and type of practice, and their knowledge about BZD
and frequency of their prescribing. In our view, a more accurate knowledge
about BZD and alternatives to its use, both factors closely linked to
training, together with the availability of non-pharmacological resources,
are likely to improve the quality of doctors prescribing habits, thus
preventing risks such as dependence of BZD. Benzodiazepines in primary
health care: a survey of general practitioners prescribing patterns,
Boixet
M, Batlle E, Bolibar I, Unitat Assistencial de Drogodependencias, Servei
de
Psiquiatria, Barcelona, Spain.
Benzodiazepines are medications that are addicting - both in combination
with other drugs and alone. The scope of the problem is thought to be
wide,
but it has not been well do***ented for unclear reasons. Pharmacologic
dependence has been do***ented in virtually all long-term users. Adverse
effects occur secondary to their use and these effects are often subtle,
but
significant. Various benzodiazepines present differences in reinforcement,
withdrawal, and adverse effects. Diagnostic issues, withdrawal, and
treatment issues are discussed. Benzodiazepines and addiction. Psychiatr
Clin North Am 1993 Mar;16(1):75-86. Juergens SM Virginia Mason Outpatient
Chemical Dependency Program, Virginia Mason Clinic.
--------------------------------------------------------------------------------
Some Highlights from The Beat the Benzos Conference, Croydon, November
2000:
Dr Nicholas Seivewright
Dr Seivewright is a psychiatrist working in the area of drug misusers. At
the end of his talk he mentioned that he felt that his profession had no
problem with reclassifying benzodiazepines (BDZs). He said that this would
solve the immediate problem of street abuse of the drugs, although there
may
be problems with other aspects of reclassification.
Dr James Robertson
Paediatrician at Arrowe Park Hospital, The Wirral. Dr Robertson said he
categorised BDZs as more dangerous than opiates or methadone to the
newborn
and that "babies affected can go on suffering for months and months" and
"that the parenting 'benzo babies' receive will be poor, not through any
fault of the parent, but the fault of the drug plus the parent".
Professor Stefan Borg
Head of Addiction Medicine, Karolinska Institute, Sweden. Professor Borg
has
been researching the biochemical changes induced by long term BDZ use. He
said extensive research in this area showed that cognitive /
psycho-neurological impairment was measurable during long term BDZ use,
increased during acute withdrawal and very slowly reverses over months or
years after cessation of the drugs. A most significant finding was that
flumazenil, a BDZ antagonist ("antidote") when given to people, who had
been
off the drugs for some time but continued with unpleasant symptoms,
improved
or were completely relieved of these symptoms. Flumazenil is a Roche
product
licensed for use in reversing the action of BDZs after anaesthesia and
overdose.
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