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Benzodiazepines (the tranquillisers and sleeping pills) made a large impact on public
consciusness in the 1980s. There was an outcry from many long-term prescribed
benzodiazepine users who discovered that the drugs were far from the panacea for
all ills they were reported to be. There was widespread media coverage in the
press and on television, a large though unsuccessful Litigation case,
new medical evidence that long term prescribed benzodiazepine use could cause
drug dependence and a burgeoning of self help groups and withdrawal clinics. As a
result there was a reduction in prescribing levels of benzodiazepines from its height
of 32 million to the present nearly 18 million prescriptions per year in the UK.
So, in 2000 the problem is generally percieved to have gone away. NHS withdrawal clinics
have shut down; the media no longer find benzodiazepines newsworthy;
very few doctors have training in benzodiazepine withdrawal methods and self help groups
receive almost no public financial support.
But the problem has not gone away; in fact it
has insidiously got worse.
[slide 2] skeleton surveying skull
The skeletons were merely shut in the closet and now some worms have been crawling out of
the woodwork.
For example, there are still around 1 million long-term benzodiazepine users in this country,
an average of over 150 in every GP practice. These people get very little help if they try
to withdraw.
There is an enormous and growing problem of illegal benzodiazepine abuse: benzodiazepines
have entered the drug scene and are used by over 90% of alcohol and illicit drug abusers.
Benzodiazepines are affecting people at all stages of life - from the elderly
who take them chronically as sleeping pills or are given them in old people's homes; to
psychaitric patients discharged into the community still taking benzodiazepines prescribed
in hospital; to young adult drug abusers; to women still being prescribed them in pregnancy
and to their developing foetuses and newborn infants
It is time for the skeletons to come out of the closet. We need to expose the bones and make
decisions about the steps needed to achieve a more rational use of benzodiazepines.
That is the main purpose of this conference.
To make a reasoned decision, we need to be clear about what benzodiazepines are and what they do.
As to what the are, their names are already well known: Librium, Valium, Mogadon, Ativan,
Xanax, Halcion and others have become houshold words that hardly need reporting. What they
do is affect the brain.BACK TO TOP
[Slide 3]GABA/BZ receptor distribution in the brain
A dose of Valium or any other BZ - rapidly enters the brain. Here the drugs react chemically
with specific molecular sites (receptors) which are widely distributed. They permeate every brain
area form the cerebral cortex (necessary for rational thought, the limbic system
(responsible for emotions), the hippocacmpus (an important centre for for memory) and the brainstem
(which controls vital bobily functions such as breathing). This chemical reaction enhances
all the effects of a natural endogenous tranquilliser.
[Slide 4] GABA action on neurones
This slide shows what GABA does to a brain cell: it stops it firing. Secondarily it reduces
the brain's output of excitatory neurotransmitters such as noraadrenaline and serotonin.
Benzodiazepines exaggerate this natural action, causing a profound biochemical disturbance
of brain function.
Activity throughout the brain is depressed, with the effects on almost every body system. This
generalised action is responsible for both the therapeutic and adverse effects of benzodiazepines.
[Slide 5] Therapeutic effects of benzodiazepines.
When used used short-term benzodiazepines are rapidly effective, relatively safe and efficient
and have a number of valuable therapeutic effects.
1. Because they quieten the brain, they make good hypnotics and sedatives.
2. Because they damp down emotions they are good anxiolytics (tranquillisers).
3. Because they decrease excitatory activity they are good anticonvulsants.
4. Because they impair memory for unpleasant events they are good to take as premadication before
surgery and for minor surgical procedures.
5. Because they relax muscles they are helpful for spastic conditions.
Because of these valuable and sometimes life saving actions there is no question of banning
benzodiepines altogether, but we do need to be very careful in prescribing them.
Adverse effects of benzodiazepines usually result from excessive dosage, interactions with other
drugs and particularly long term use. I will mention some of these, though most of them will be
familiar to the audience.BACK TO TOP
[Slide 6] Acute toxicity of benzodiazepines.
Benzodiazepines have always been regarded as remarkably non-toxic drugs. However, they are
not completely safe. They are involved in up to 40% of all self poiisoning incidents.
Between 1980 and 1989 there were 1512 suicides attributed to benzodiazepine overdose.
In 2/3 of these cases the drug was taken alone, in 1/3 with alcohol.
Temazepam, the commonest hypnotic used today, turned out to be the most toxic. The risk of a
fatal outcome form benzoidazepine overdosage is greatly increased in the elderly and
in people with lung disease, and benzoidazepines increase the risks of fatality if taken
with many other drugsnot included in this analysis. The combination of benzodiazepines
with opiates causes almost 100 deaths each year among drug abusers in Glasgow alone.
The cause of benzodiazepine fatalities is depression of respiration: They impair function in brain
centres vital for breathing.
[Slide7] Oversedation.
Oversedation is a dose-related extension of the sedative/hyhpnotic effects of benzodiazepines.
Symptoms include drowsiness, poor concentration, mental confusion, muscle weakness and
impaired balance and coordination. These symptoms may persist as "hangover" effects from
hypnotics taken at night and long-acting benziduazepines taken regularly tend to accumulate
in the body. For example, active metabolites of diazepiam(Valium) are present in the body
200 hrs (over a week) after a single dose.
Elderly patients are most vulnerable to oversedation, but it can also occur in young people
and the effects are additive with other depressant drugs including alcohol, cannabis, and
some prescribed drugs.
These effects have been shown to contribute to falls and fractures in the elderly,
to traffic accidents and other accidents at home and at work. A recent study published in the
Lancet estimated that benzodiazepines cause 1600 traffic accidents and 110 driving-related deaths
each year in the UK.
Slide[8] Impairment of memory.
Benzodiazepines specifically impair memory functions. They make it difficult to learn and
retain new information and in particular cause amnesia for recent events. These effects are
again most marked in elderly patients and may falsely lead to a diagnosis of dementia or
Altzheimer's disease. Professor Lader remarked in 1995 that forgetfulness, amnesic
episodes or confusion should not be ascribed facilely to ot 'old age' or 'dementia'in older patients
taking benzodiaepines. Yet many occupants of homes for the elderly are prescribed benzodiazepine
hypnotics. Case studies show that memory improves when these are stopped and sleep is also
better.
In younger people benzodiazepines can also cause memory lapses or blackouts and have
led to patients being charged with shoplifting.
Benzodiazepines are often prescribed for acute stress-related anxieties and may indeed provide
initial relief from distress in catastrophic accidents and bereavement. However, continued
use can impair psychological adjustment to such trauma, leaving the situation unresolved
and the symptoms perpetuated. In anxiety states, including panic disorders and agoraphobia,
benzodiazepines inhibit the alternative stress-coping strategies including cognitive
behavioural
treatment.BACK TO TOP
[Slide 9] Emotional effects:
agression, depression, emotional blunting.
Like alcohol, can occasioinally cause apparently paradoxical stimulation with increased
agression, anger, violence and antisocial behaviour. Benzodiazepines have been linked with
baby-battering, 'wife beating' and 'grandma bashing'. Less dramatically, increases in irritability
and argumentativeness are often remarked on by patients on long-term benzodiazepines and by their
families. These effects are thought to result from disinhibition usually controlled behaviour.
On the other side of the coin, benzodiazepines can actually cause depression: most long-term
benzodiazepine users, like alcoholics, are depressed. Benzodiazepines can also aggravate
depression if already present and can precipitate suicidal tendencies in such patients.
For this reason the Committee on Safety of Medicines recommended in 1988 that benzodiazepines
should not be used to treat depression or anxiety associated with depression though they
are still prescribed for depressed and anxious patients.
Another long-term use of theses drugs is to "emotional anaesthesia", a blunting of the
ability to feel pleasure or pain or to empathise with others. Former long-term benzodiazepine
users often bitterly regret their lack of emotional response to family events while they were
taking these drugs. Children brought up in such households often say things like "it was
no use telling mother anything; she could't understand what we wrere feeling and wouldn't
remember it anyway." - a mixture of emotional blunting and impairment of memory caused by
the benzodiazepines.BACK TO TOP
[Slide 10] Effects in pregnancy.
Benzodiazepines cross the placenta and if taken regularly by the mother, even in therapeutic
doses, have adverse effects on the foetus and neonate. The developing and newborn baby
metabolise benzodiazepines very slowly so that appreciable concentrations may persist
for two or more weeks after birth, resulting in the "floppy infant syndrome" with
poor muscle tone and difficulties in breathing and suckling. Infants regularly exposed to
benzodiazepines in utero may also develop delayed withdrawal symptoms with
irritability, crying and feeding difficulties.
There is some evidence that benzodiazepines taken maternally during pregnancy may
impair intrauterine growth and may possibly contribute to cot deaths and later
neurological abnormalities.
[Slide 11] Weight, height and head circumference in infants exposed to benzodiazepines
in utero.
This slide shows the findings of a Swedish study {Laegried et al 1992) of 17 children
whose mothers had taken prescribed doses of benzodiazepines during pregnancy. The exposed
infants had lower birth weight, length and head circumference than the babies of control groups.
By 19 months the exposed infants had nearly caught up with the others in height and weight,
but not in head circumference. Five of the children had abnormalitites similar to those of
alcoholic mothers. We are still waiting for a follow up, but there is a suggestion from user
groups in this country that such children may be a t risk in later life of attention
deficit disorder and possibly a spectrum of autistic disorders. This would be consistent with
animal work which shows that intrauterine exposure to drugs which affect the brain can
impair its normal development with lasting cognitive and behavioural impairments.
BACK TO TOP
[Slide12] Benzodiazepine dependence.
Then we come to benzodiazepine dependence, a subject no doubt close to the hearts of many people
here. There is no doubt that benzodiazepines are potentiolly addictive drugs. With regular use
for only a few months or even weeks the body comes to depend on them both psychologically and
physically for normal function. A degree of tolerance develops so that larger doses are
needed to produce the initial effects. If dosage is insufficient, because of tolerance, if
the dosage is reduced, or if the drug is stopped withdrawal symptoms develop. Long term users,
even while continuing drug use, suffer from both the adverse effects I have already mentioned
and also from withdrawal psychological and physical effects. In fact long-term use is
commonly accompanied by increasing illness.
[Slide 13] Morbidity in 50 patients.
This slide shows some of the symptoms in 50 consecutive patients attending my benzodiazepine
withdrawal clinic in the 1980s. They had been on so called "therapeutic doses" of
benzodiazepines for 5 - 20 years and wished to withdraw because they did not feel well.
While taking the drugs :
- 20% had taken drug overdoses requiring hospital admission.
- 20% had developed incapacitating agoraphobia (in addition to the vast amjority who had panic attacks).
- 18% had undergone GI investigations (irritable bowel).
- 10% Had undergone neurological investigations. (3 wrongly diagnosed with ME).
In addition, 62% had received other psychotropic drugs (mainly antidepressants) since starting
benzodiazepines and 28% were taking a combination of two benzodiazepines.
These symptoms were not the original cause for starting benzodiazepines, but developed during
the course of prolonged use. It seems clear that long-term benzodiazepines actually aggravate
or cause further anxiety or depression. In this series over 90% of the patients
withdrew successfully and after withdrawal, there were no more overdoses, agoraphobia, panic
attacks and neurological symptoms disappeared. The fact that patients improve after withdrawal
is a strong argument that these symptoms were related to the benzodiazepines and were not
due to some underlying psychiatric disorder as many psychiatrists have claimed. There are
no doubt people in the audience who can attest to this experience.
BACK TO TOP
[Slide 14] Acute withdrawal syndrome.
I will not say much about withdrawal symptoms or the management of benzodiazepine withdrawal
since these topics will be dealt with by other speakers. Acute withdrawal symptoms are largely
the opposite of the initial therapeutic actions so that hypnotic effects are replaced
by insomnia, tranquility by increased anxiety, muscle relaxation by increased muscle
tension and spasms. There are also many physical symptoms such as pain, numbness,
muscle tension and twitches.
[Protracted withdrawal symptoms.
In some subjects the withdrawal syndrome can be protracted, lasting months or even years.
Protracted symptoms include insomnia, depression and a variety of neurological and
gastrointestinal symptoms which can be very distressing and may sometimes be permanent.
There is no time to go into the symptoms in detail, but they have raised the question of whether
long-term benzodiazepine use can cause permanent cognitive or neurological damage.
So far there is no clear evidence of structural damage to the brain, though it has been suggested in
some studies. Other studies have clearly shown long-lasting, cognitive deficits in long-term
benzodiazepine users who have withdrawn.
[Slide 16] Memory tests in ex-benzodiazepine users.
(Gorenstein et al. 1995)
A recent study looked at cognitive performance in 28 patients who had taken prescribed low dose
benzodiazepines for a mean of 10 years.
Compared with a matched group of anxious patients not on benzodiazepines and healthy volunteers.
The benzodiazepine patients were tested before withdrawal and 3 weeks and 10 months after
withdrawal. This slide shows the results on simple memory tests (digit span forwards
and backwards, immediate and delayed story recall). As you can see, the benzodiazepine patients
were impaired before and still 10 months after withdrawal compared to the control groups.
Many ex-benzodiazepine users complain that it is years before their mental capacity returns.
BACK TO TOP
[Slide 17] Illicit benzodiazepine abuse.
The most recent and possibly the most menacing worm crawling out of the woodwork is that
of so-called recreational benzodiazepine abuse. There are probably over 100,000 illicit
benzodiadepine abusers in the U.K., and the number is still rising.
Up to 90% of opiate, cocaine and amphetamine users report that benzodiazepines increase the
"high" obtained from opiates and alleviate the withdrawal effects when supplies are limited.
Users of of stimulants such as cocaine, amphetamines and even ecstasy use benzodiazepines
use "downers" to overcome the effects of their "uppers". Benzodiazepines have already
crept into the "rave" scene.
Benzodiazepines are already used by alcoholics attending for detoxification and are often
obtained illegally. They are taken partly to alleviate the anxiety associated with alcohol use,
but also because the mixture of alcohol and benzodiazepines produces a desirable effect.
Temazepam and lager is a popular combination.
There are also some who use benzodiazepines alone or as their main drug because they have
discovered that high doses can give them a kick. Just about all the benzodiazepines can be
used and delivered orally, by injection or snorted as snuff. Temazepam is the most popular
benzodiazepine in the U.K. and intravenous users in Liverpool reported injecting over 3000
mgs in one go. They said that such injections not only provide a "buzz" and relaxation,
but also give confidence to engage in criminal activities.
Some street users have moved on to taking large amounts of oral benzodiazepines in combination
with injected opiates such as buprenophine. This combination, temazepam and Temgesic (Tem-Tem)
causes about 100 deaths in Glasgow alone. A popular youth craze is to ride on the buses all
day in gangs "wobbling" on oral temazepam fortified by high strength lager and cannabis.
Needless to say these practices are not without adverse effects.
Complications of IV injection included abscesses and venous and arterial thrombosis.
When their arms are affected, users may progress to injecting in the groin and this has
resulted in gangrene.BACK TO TOP
[Slide 18] Eye complications.
This subject who had a leg amputation because of gangrene, injected temazepam into his
eye and became blind in both eyes as a result. Injecting users are also at risk of
hepatitis and HIV infection.
Both oral and IV users suffer blackouts and cognitive impairments. Benzodiazepine
users appear to be particularly prone to needle-sharing and risk-taking sexual behaviour,
increasing the risk of HIV infection. In any resulting pregnancies the foetus is at
extra risk because of the high doses used. Thus the effects are passed to the
next generation.
like therapeutic dose users, benzodiazepine abusers become dependent and can suffer
severe withdrawal effects including withdrawal fits.
The tragedy about benzodiazepine abuse is that it is our own fault. It could have been
foreseen and could have been prevented. The history of benzodiazepine abuse is the same
as that of the amphetamines. Mandrax, glutethamide and many others originated as prescribed
drugs and later entered the drug scene. In the case of benzodiazepines a couple of decades
of widespread prescribing elapsed before the abuse potential was discovered at a time when
benzodiazepines were lying around in nearly every household. Within a few years they became
the most widespread of IV drugs of abuse in the U.K.
The source is almost entirely from pharmaceutical supplies and from prescriptions. Some users
attend several GPs for the drugs; some GP patients (often elderly) sell their supplies, some
children obtain them from their parents' prescriptions; and large amounts are stolen from
chemists and warehouses. Benzodiazepines are still cueap and easy to obtain on the street.
Now diazepam, temazepam and other benzodiazepines are coming in from Europe, a signal that it
may already be too late to prevent illegal benzodiazepine abuse.
At present benzodiazepine abusers are small in numbers compared to the number
of prescribed long-term users and also ex-users whose lives are also affected,
sometimes permanently, but they add urgency to the need to rationalise benzodiazepine
prescribing.
BACK TO TOP
[Slide 21] Steps needed to reduce benzodiazepine prescribing.
We need urgently to:
1. Impress upon doctors the need to adhere to short-term prescriptions if benzodiazepines
are indicated in new patients (2 weeks only in minimal dosage).
2. Educate Doctors, pharmacists and other health care workers in the managemanet of
benzodiazepine withdrawal in long-term users.
3. Provide financial aid for benzodiazepine support groups and withdrawal clinics. Also
residential accommodation.
4. Seriously consider rescheduling benzodiazepines.
5. Educate doctors and the public about prescribing new drugs with abuse potential (eg.
Zopiclone and Zolpidem, non-benzodiazepines which have already caused addiction problems
and perhaps also need to rescheduled).
These and related questions will be addressed by other speakers.
[Slide22] Socioeconomic costs of inappropriate benzodiazepine use.
Finally this slide summarises some of the socioeconomic costs of inappropriate benzodiazepine
prescribing.( enumerate slide)
Curbing benzodiazepine prescriptions would not only save the NHS millions of pounds, but would
also help to allay and prevent the suffering of current and potential prescribed and illicit
benzodiazepine users. Public pressure, such as we have here in this campaign , combined with
reasonable suggestions about the actions required may be the best way to influence current
practices.BACK TO TOP
REPRODUCED WITH KIND PERMISSION FROM THE AUTHOR
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