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#Post#: 1155--------------------------------------------------
DRUGS - HISTORY - USE AND ABUSE - DOCTOR AND PATIENT MISTAKES
By: AGelbert Date: May 19, 2014, 2:43 pm
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[move] [font=courier]History of Benzodiazepines: What the
Textbooks May Not Tell You
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[/font] [/move]
Presentation by C. Heather Ashton, DM, FRCP
at the 3rd Annual Benzodiazepine Conference,
Bangor, Maine, October 12, 2005
These are the speaking notes and links to accompanying
PowerPoint® slides presented by Prof. C. Heather Ashton, DM,
FRCP, at the 3rd Annual Benzodiazepine Conference, in Bangor,
Maine, October 11–12, 2005. The documents are published here
with the permission of Prof. Ashton. Copyright for these
materials resides with Prof. Ashton.
Early history of anxiolytic drugs
Title Slide
Slide 1
History has an inexorable way of repeating itself. It has always
been a surprise to me that we have allowed history to repeat
itself in medicine, when we could so easily learn from our
mistakes. Here are some drugs which have been used medicinally
to relieve anxiety and promote sleep throughout the ages:
Anxiolytic Drugs Through the Ages
Slide 2
Alcohol use goes back about 8000 years. The Bible tells us that
“Noah planted a vineyard — drank of the wine and was drunken.”
Later alcohol was used medicinally as an anxiolytic though it
was abused by some. In the Middle Ages, alchemists hailed
alcohol as the long-sought elixir of life. But by the 18th
century, with the introduction of cheap gin and the rise of gin
palaces, the addictive properties of alcohol became widely
recognised.
Opium also has a history extending over thousands of years and
was taken to relieve anxiety. Sydenham in 1680 described it as
the most universal and efficacious of all the “remedies which it
has pleased Almighty God to give to men to relieve his
sufferings.” But its addictive properties became apparent and in
the 19th century De Quincy dubbed it the “dread agent of
unimaginable pleasure and pain.”
Bromides were widely used as sedatives in the 1870s. They were
also prescribed for epilepsy because they lessened sexual urges
and epilepsy was thought to be a consequence of mas tur bation.
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But the
dependence potential again became apparent.
Chloral hydrate and paraldehyde were synthesised around this
time and introduced as sedatives, but both became associated
with abuse and dependence.
Then came the barbiturates, introduced as hypnotics and
sedatives between 1903 and 1912. The dependence-producing
properties became increasingly apparent, together with alarm
over the dangers of overdose. This led eventually in the 1970s
to a campaign to replace them with benzodiazepines.
Meanwhile, other compounds with similar properties were
introduced including ethylchlorvynol, carbromal, glutethimide,
methyprylon and methaqualone, but their dependence potential and
toxicity was soon recognised.
Benzodiazepines were discovered, more or less by chance, by
Sternbach, working for Hoffman La Roche in New Jersey. In 1957
the original compound was found to have hypnotic, anxiolytic and
muscle relaxant effects and the first benzodiazepine,
chlordiazepoxide (Librium) was launched in the UK in 1960,
followed by diazepam (Valium) in 1963. By 1983 there were 17
benzodiazepines on the market worth nearly $3 billion worldwide.
There are now 29 benzodiazepines available in Europe and the
USA. I have already sketched the later history of
benzodiazepines, yesterday, and the tardy realisation that they
too, were dependence-producing and will say a bit more about it
later today.
Now we are faced with the introduction of the Z drugs, zopiclone
(introduced in 1998), zolpidem and zaleplon (in 2000) and now
eszopiclone (in 2005). They act like benzodiazepines. Do we
really think that they are free of dependence potential and
abuse? I will return to this point later.
By the late 1970s benzodiazepines had become the most commonly
prescribed of all drugs in the world. It was estimated that one
in five of all women and one in ten of all men in Europe took
them at some time each year. The drugs were prescribed
long-term, often for many years, for complaints such as anxiety,
depression, insomnia and ordinary life stresses.
But in the early 1980s in England long-term prescribed users
themselves realised that the drugs tended to lose their efficacy
over time and instead became associated with adverse effects. In
particular, patients found it difficult to stop taking
benzodiazepines because of withdrawal effects, and many
complained that they had become "addicted." Throughout the 1980s
there was a public outcry against benzodiazepines in the U.K.
resulting in widespread media coverage in the press, radio and
television and a burgeoning of self-help groups and withdrawal
clinics.
#Post#: 1156--------------------------------------------------
Re: DRUGS - HISTORY - USE AND ABUSE - DOCTOR AND PATIENT MISTAKE
S
By: AGelbert Date: May 19, 2014, 2:59 pm
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[I]Continued from previous post by Dr. as well as a Prof) Ashton
8) [/I]
History of My Benzodiazepine Withdrawal Clinic
My own involvement with benzodiazepines started at this time.
One day in 1981 a lady came hobbling on crutches into my general
pharmacology clinic. She had been involved in a road traffic
accident. She had two broken limbs in plaster and had been
prescribed the benzodiazepine Ativan for muscle relaxation (1mg
tds). She had noticed as she recovered that when the time for
each dose of Ativan approached she experienced a strong craving
for the next pill, along with anxiety, restlessness and muscle
cramps. "I think I am addicted," she said. "Can you help me?"
Naively I said "yes" although I had no experience in drug
addiction at that time. She duly underwent a withdrawal process,
during which she suffered many symptoms including anxiety,
insomnia, hallucinations; tremor, muscle cramps and many other
symptoms now (but not then) recognised as typical benzodiazepine
withdrawal symptoms.
Following this lady's appearance at my clinic there was a
trickle of others which soon grew to a stream and finally a
flood of patients referred by their doctors because they wished
to stop their benzodiazepines. As a result, I had to start a
dedicated benzodiazepine withdrawal clinic. I continued this
clinic single-handedly for 12 years at two sessions every week
until 1994 when I had to retire (you have to retire at 65 from
clinical work under the National Health Service). Strangely,
none of my medical colleagues wished to become involved in this
clinic or to take it over in 1994, so the clinic closed down. I
think that the current medical training did not equip most
doctors for listening to anxious patients with many complaints,
patients who were time-consuming and required repeated
consultations. I myself spent most of the time simply listening
to the patients and learning from them how to come off
benzodiazepines.
Adverse Effects of Long-Term Benzodiazepine Use
Over 300 patients passed through this clinic and over 90%
successfully withdrew.
Morbidity in 50 Patients
Slide 3
This slide shows some of the symptoms in the first 50 patients
attending the clinic. They had been on prescribed, so-called
"therapeutic" doses of benzodiazepines for 1–22 years (mean, 10
years) and wished to withdraw. They ranged from 20 to 72 years
of age, (mean age 46 yrs); 40 were females.
•20% had taken drug overdoses requiring hospital admission in
suicide attempts (illustrating that benzodiazepines cause or
exacerbate depression)
•20% had developed incapacitating agoraphobia (in addition to
the majority who had panic attacks)
•18% had undergone GI investigations (irritable bowel) (a
condition closely linked to anxiety)
•10% had undergone neurological investigations (3 wrongly
diagnosed with MS on the basis of muscle weakness and tremor,
blurred vision and patches of numbness — signs often associated
with anxiety states)
•62% had been prescribed other psychotropic drugs, mainly
antidepressants, since starting benzodiazepines
•28% were taking a combination of two benzodiazepines, the
second added after the first become insufficient.
This illustrates the development of tolerance and dosage
escalation with 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 and depression. In the 90% of
patients in this series who successfully withdrew, and I
followed for 10 years, there were no more overdoses; the
agoraphobia, panic attacks, depression and neurological
symptoms, including the alleged MS, disappeared. The fact that
patients improve after withdrawal is a strong argument that
symptoms are related to the benzodiazepines and are not due to
some underlying psychiatric disorder, as many psychiatrists have
claimed. :o
Some of these patients developed withdrawal symptoms while
coming off benzodiazepines. Between 1980 and 1985 a number of
controlled trials by Lader, Tyrer and others showed that
withdrawal symptoms from regular therapeutic doses of
benzodiazepines were real and that they indicated dependence on
these drugs.
Benzodiazepine Withdrawal Symptoms
Withdrawal Symptoms
Slide 4
These have since been described by many authors and include a
range of symptoms common to all anxiety disorders (such as panic
attacks, agoraphobia, insomnia, nightmares, tremors and muscle
tension) and some relatively specific to benzodiazepines (such
as perceptual distortions, hallucinations, sensory
hypersensitivity and sometimes psychotic symptoms). However,
these symptoms are not obligatory if withdrawal is carried out
slowly and carefully — as I shall describe later. They nearly
always improve after some weeks although in a small proportion
the symptoms may be protracted.
Protracted Withdrawal Symptoms
Slide 5
Anxiety, depression and gastrointestinal symptoms may persist
for many months, though gradually declining. A number of
neurological symptoms including tinnitus, motor and sensory
symptoms and global cognitive impairment may be very
long-lasting and raise the question of whether benzodiazepines
may cause permanent neurological damage.
The publicity surrounding benzodiazepines in the 1980s resulted
in a reduction of benzodiazepine prescribing levels in the UK
from its height of 32 million in 1976 (for a population of 50
million) down to about 18 million in 2000. And by 2000 the
benzodiazepine problem was largely perceived to have gone away.
National Health withdrawal clinics had shut down, the media no
longer found benzodiazepines newsworthy and self-help groups
closed down because of lack of public financial support.
Skeleton in the Closet: Costs of Inappropriate Prescribing >:(
[move][font=courier]But the problem has not gone
away.[/font][/move]
Skeleton Surveying Skull
Slide 6
The skeletons were merely shut in the closet and now some worms
are beginning to crawl out of the coffin. For example, there are
still nearly one million long-term benzodiazepine users in the
UK and four million or more in the US. There is a growing
problem of benzodiazepine abuse — benzodiazepines are taken by
over 90% of alcohol and illicit drug abusers and sometimes in
their own right. Benzodiazepines are inappropriately prescribed
at all stages of life — from the elderly who take them
chronically as sleeping pills or are given them to keep them
quiet in retirement homes and psychiatric units; to discharged
psychiatric patients still taking benzodiazepines prescribed in
hospital; to women still being prescribed them in pregnancy, and
to their developing fetuses and newborn infants.
There are large and uncounted socioeconomic costs associated
with benzodiazepines.
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Reasons for Inappropriate Benzodiazepine Prescribing
Why are benzodiazepines still so commonly prescribed
inappropriately? One factor is that doctors have failed to
follow guidelines limiting them to short-term usage. In the
short-term, that is 2–4 weeks only or intermittent use,
benzodiazepines have many excellent therapeutic, even
life-saving properties, illustrated here (enumerate).
Therapeutic Actions of Benzodiazepines (Short-Term)
Slide 8
(enumerate)
Used long-term, however, they can produce many adverse effects
that I have no time to describe in detail. They include:
(enumerate)
Adverse Effects of Benzodiazepines (Long- Term)
Slide 9
Doctors have been slow to give up the idea that benzodiazepines
are so benign that they can be continued for life.
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Secondly, doctors and drug companies have been slow to recognise
the difference between different benzodiazepines, both in rates
of elimination and in relative potency.
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This slide shows
equivalent potencies and elimination rates of some anxiolytics.
Equivalent potencies of different benzodiazepines
Half-lives and Equivalent Potencies of Benzodiazepine
Anxiolytics
Slide 10
Explain slide (elimination half-lives and approximate clinical
potency of some benzodiazepines compared to diazepam).
The three most potent in this group of anxiolytics are
alprazolam, clonazepam and lorazepam which are 10–20 times more
potent than diazepam. :o This difference is often disregarded
and the drugs prescribed in excessive dosage. For example, I
have recently seen patients prescribed alprazolam in daily doses
of 4–6mg — equivalent to 80–120mg of diazepam. Alprazolam is no
longer prescribed under the NHS in the UK though it can be
prescribed privately. I have also recently seen lorazepam
prescribed in 6, 10, and over 12mg daily doses — again in
equivalence up to 120mg diazepam. Both these drugs are fairly
short-acting and have to be taken 3–4 times a day. Patients
often suffer mini-withdrawal symptoms between doses. Clonazepam
is also very potent, 10–20 times the strength of diazepam. In
the UK it is only officially indicated as an anticonvulsant for
epilepsy but it is popular in the US and British doctors are
following suit and prescribing it for anxiety.
All these three drugs are highly addictive; :P dependence
develops rapidly and they are particularly hard to withdraw
from. This difficulty is partly due to the relatively excessive
dosage used, partly I suspect from their potency which probably
means that they bind particularly avidly to GABA/BZ receptors,
partly because equivalent potencies are not adhered to when
switching patients to other benzodiazepines such as Valium or
Librium in attempts at withdrawal, and partly because they are
not available in small enough dosage strengths to allow for
gradual dosage reduction. In the UK Ativan is only available in
2.5mg or 1mg tablets. The 1mg tablet is equivalent to 10mg
diazepam. Even if you halve it you are withdrawing by decrements
of 5mg in diazepam equivalents, which can be a big drop for some
people. Strangely, 0.5mg Ativan tablets are available in the US
and Canada, but all attempts to get the drug company (Wyeth) to
supply this in the UK have failed.
Many physicians in the US switch patients on alprazolam or
lorazepam onto clonazepam for withdrawal in the belief that its
longer half-life will make withdrawal easier. However, clinical
experience shows that clonazepam is also difficult to withdraw
from, and patients do much better switching onto diazepam which
has a much longer half-life including active metabolites for up
to 200 hours, allowing a smoother and slower fall in blood
concentration. Also diazepam comes in 1mg tablets which can be
halved allowing very small dosage decrements. Yet for some
reason I have found that American doctors are very reluctant to
prescribe diazepam. ???
I will describe withdrawal methods in more detail later. First
you may ask how these equivalents were arrived at. Most were
determined by direct clinical titration. In about 1983 Professor
Michael Rawlins and I in Newcastle titrated the dose of diazepam
required to substitute, in terms of anxiety symptoms, in 20
anxious patients on various doses of lorazepam. The mean came to
an equivalence of 9.8mg diazepam for 1mg lorazepam. This is
close to the equivalence of 1:10mg now officially accepted in
most texts. Similar clinical tests were conducted for other
benzodiazepine such as alprazolam though some equivalents are
based on clinical experience during withdrawal of patients on
various benzodiazepines who were switched to diazepam. Some
equivalents were derived from animal work and human trials by
drug companies. There is now a general consensus, at least in
the UK, about equivalent potencies for both anxiolytic and
hypnotic benzodiazepines. They are quoted in the British
National Formulary produced by the British Medical Association
and the Royal Pharmaceutical Society circulated to all doctors
and in many published papers. Unfortunately, not all doctors
read or heed this advice!
Half-lives and Equivalent Potencies of Some Benzodiazepine
Hypnotics
Slide 11
This slide shows the equivalences and half lives of some
benzodiazepine hypnotics. Triazolam is very potent, again 20
times the strength of diazepam and very short acting. It can
give rise to withdrawal symptoms the next day, and it was
removed from the UK formulary in 1995. Flunitrazepam is also
potent but long-acting. It gained general popularity as a
“date-rape” drug, because of the prolonged amnesia it induces.
Nitrazepam, temazepam and flurazepam are less potent and have a
medium duration of action but can cause a hangover the next day.
All these equivalencies are of course approximate. There is
considerable individual variation in how people react to
benzodiazepines. In addition, there are subtle differences in
the pharmacological profiles of different drugs, and the
equivalences do not always work at higher doses. For example, in
my clinical experience diazepam is rather more sedative than
lorazepam (Ativan) which is more anxiolytic. So if you abruptly
change someone on say 6mg Ativan to 60mg of diazepam, he is
likely to become very sleepy but may still be anxious. However,
you can accomplish a changeover if you do it gradually and
stepwise, dose by dose, titrating each dose to the clinical
response. People also have differences in the speed at which
they metabolise drugs, but on the whole the equivalences apply
generally, except possibly in the case of benzodiazepines which
have active metabolites such as diazepam where the half-lives of
these can vary from 36–200 hrs.
#Post#: 1157--------------------------------------------------
Re: DRUGS - HISTORY - USE AND ABUSE - DOCTOR AND PATIENT MISTAKE
S
By: AGelbert Date: May 19, 2014, 3:22 pm
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Last part of Good Info on Benzos and other drugs in common use
AND ABUSE [img width=40
height=40]
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/>
Patients at Special Risk from Benzodiazepines
Individual differences apply more to the third reason why
benzodiazepines are prescribed inappropriately, which is when
they are given in the wrong dose to the wrong people.
Vulnerable Patients
Slide 12
The elderly are especially susceptible to the sedative effects
of benzodiazepines which may cause mental confusion, cognitive
impairment suggesting dementia and ataxia leading to falls and
fractures. This is partly because of reduced metabolism,
especially oxidation and partly because of increased central
nervous system vulnerability. Benzodiazepine dosage for elderly
patients should always be half of the adult dose, and
benzodiazepines which are not oxidised but conjugated, such as
oxazepam and temazepam are preferred. Patients with chronic
respiratory or liver disease are at increased risk of
respiratory depression, which can be fatal, and oversedation and
benzodiazepines are relatively contraindicated in these cases.
Benzodiazepines should be avoided in patients with depression
which they may aggravate and increase the risk of suicide.
Additive effects may occur with patients taking other depressant
drugs such as alcohol or sedative antidepressants. In pregnancy
there is a risk of adverse effects on the fetus, neonatal
depression (floppy baby syndrome) and neonatal withdrawal
effects. Patients with a history of alcohol or drug abuse or
those with personality disorder may be more likely to become
dependent. There are also genetic differences in drug
metabolism. Slow metabolism of benzodiazepines, and also of
alcohol, is common in Orientals, and the recommended dose of
benzodiazepines in Hong Kong, for example, is half that
recommended in Europe and North America. On the other hand, some
drugs such as barbiturates and nicotine in smoking induce liver
enzymes, increasing the rate of metabolism. Benzodiazepines are
not enzyme inducers but the rate of metabolism may be affected
by other drugs which induce or inhibit liver enzymes
(ketoconazole). Finally tolerance to previous benzodiazepine
use, alcohol or barbiturates may reduce sensitivity to
benzodiazepines.
With all these caveats for benzodiazepines, what about the more
recently introduced “Z drugs”—zopiclone, zolpidem, zaleplon and
now the introduction of eszopiclone (Lunesta)?
The Z Drugs
Half-Lives and Equivalent Potencies of Z-Drugs
Slide 13
These are not chemically benzodiazepines but they bind to GABA
receptor complexes which are close to or actually coupled with
benzodiazepine receptors. They are said to be more selective,
binding mainly to the a1 GABA receptor subtype which mediates
the hypnotic effects of benzodiazepines. In practice they are
not all that selective and have much the same actions as
benzodiazepines. In the UK, the National Institute for Clinical
Excellence (NICE), which advises the Health Service on optimum
drug use, recommended that Z drugs should be used for short-term
treatment only (2–4 weeks) and then only as second line
treatments after benzodiazepines. They concluded that the Z
drugs produced the same therapeutic and adverse effects as
benzodiazepine hypnotics, including tolerance, dependence and
abuse, and were also more expensive.
As a clinical example, a psychiatrist recently asked my advice
about the nursing sister he was helping to withdraw from
lorazepam (Ativan). She developed quite severe withdrawal
symptoms as the dosage was lowered and had trouble sleeping. To
help her, the psychiatrist prescribed zopiclone (Zimovane) to
take at night. She found that this drug completely relieved her
withdrawal symptoms. In fact, it was so successful that she
started taking zopiclone in the daytime as well. She ended up
taking zopiclone six times a day as well as at night, ending up
with a total dose of over 40mg/day (the recommended dose is
7.5mg at night). The psychiatrist was chagrined to find that he
had merely replaced one form of addiction with another. :P
There are a number of cases in the literature of such escalation
of dosage with zopiclone, followed by dependence and withdrawal
symptoms on stopping. There are also an increasing number of
cases reported of misuse and abuse of high doses of zolpidem
(Ambien). This can result in hallucinations and psychosis and is
reminiscent of the adverse effects of triazolam (Halcion), the
short-acting benzodiazepine hypnotic now banned in the UK.
Now eszopiclone is being promoted for long-term use and the
manufacturers report trials lasting two weeks to six months of
its hypnotic effects. They report little tolerance or loss of
efficacy over these periods and a low incidence of rebound
insomnia or anxiety (3.7%) on stopping. Euphoria was noted in
high doses, suggesting an abuse potential. I remain sceptical of
these results which involved relatively small numbers of
subjects with various types of insomnia. I am not convinced that
eszopiclone is all that different from zopiclone, apart from its
potency, and I think it would be prudent to limit it to
short-term use until proved otherwise.
There is a basic pharmacological principle that any drug which
acts on intrinsic body receptors will cause adaptive changes in
these receptors if used chronically. This is because the body
is programmed to restore homeostasis if its internal environment
is disturbed. For every drug action in the body there is an
equal (as far as possible) reaction which tends to restore the
status quo. This mechanism underlies the development of drug
tolerance and dependence and also of withdrawal reactions if the
drug is stopped. It applies not only to benzodiazepines but also
to non-psychotropic drugs like B blockers. For example, B
blockers such as propranolol are used to slow the heart and
lower the blood pressure. If these are suddenly stopped there is
a rebound of increased heart rate and raised blood pressure. We
accept that tolerance and withdrawal reactions occur with
benzodiazepines, barbiturates and all the hypnotic and sedative
drugs that have gone before. We even understand much about the
molecular mechanisms involved — which I won't go into here.
There seems no reason to believe that these reactions will not
apply to Z-drugs.
I suspect that the Z-drugs will undergo the fate of many newly
introduced drugs — a fate that is becoming all too familiar. :(
Historical Evolution of New Drugs
Slide 14
Management of benzodiazepine withdrawal
So how should we withdraw benzodiazepines in people who have
become dependent through long-term use? I have already described
this is some detail elsewhere. I make no claims that this is the
last word in benzodiazepine withdrawal, but the methods are
based on experience in my withdrawal clinic and on many other
patients I have been in contact with since then.
Benzodiazepine Withdrawal
Slide 15
The basic principles for people withdrawing from therapeutic
doses of benzodiazepines are simple: gradual dosage reduction
and anxiety management if needed. It is generally agreed that
dosage should be tapered gradually. Abrupt withdrawal,
especially from high doses, can precipitate convulsions, acute
psychotic or confusional states and panic reactions. The rate of
tapering should be tailored to the patient's individual needs,
taking into account lifestyle, personality, environmental
stresses, reasons for taking benzodiazepines, amount of support
available and other personal factors. Various authors suggest
optimal times of 6-8 weeks to a few months for the duration of
withdrawal, but some patients may take a year or more. The best
results are achieved if the patient himself (not the doctor) is
in control of the rate of withdrawal and proceeds at whatever
rate he or she finds tolerable. The doctor and patient together
can devise a mutually agreed withdrawal schedule, but this may
require readjustments from time to time according to progress.
If problems arise, either in the form of increased symptoms or
extra environmental stresses, it may be necessary to stabilise
the dosage for a few weeks or to reduce the rate of withdrawal.
But it is important always to go forwards, avoiding a backward
step of increasing the dosage again.
The size of each dosage reduction depends on the starting dose.
Patients on higher doses can usually tolerate larger dose
decrements than those on lower doses. For patients taking less
than 20mg diazepam or equivalent, reductions of 1mg every 1-2
weeks are generally tolerated. When dosage is down to 4–5mg
diazepam or equivalent, decrements of 0.5mg may be preferred. On
the other hand, initial dosage reductions of 2mg every 1–2 weeks
may be appropriate for patients starting on 40mg diazepam or
equivalent.
Stopping the last few milligrams is often seen by patients as
particularly difficult, because of fears of how they will cope
without any drug at all. However, the final parting is often
surprisingly easy, especially as confidence increases during
withdrawal, and patients are encouraged by their new sense of
drug-free freedom.
For most patients on therapeutic doses of benzodiazepines
withdrawal is best carried out as an outpatient. Rapid
withdrawal in detoxification clinics, even with phenobarbitone
substitution, is inappropriate because the patient has no time
to build up alternative living skills, which may take many
months. Detoxification in drug and alcohol clinics is utterly
inappropriate and traumatic for people involuntarily addicted to
benzodiazepines by doctors' prescriptions.
The general aim of the dosage tapering strategy is to achieve a
smooth, slow, steady fall in blood concentration of
benzodiazepine, allowing time for the body to adjust to the
change. This slow, smooth decline is not possible with rapidly
eliminated benzodiazepines like lorazepam, (Ativan) or
alprazolam (Xanax) with which blood concentrations fluctuate
with peaks and troughs between each dose. It is therefore often
advisable for those taking these drugs to switch to diazepam.
When doing so, it is important to keep in mind the equivalent
potencies that I have mentioned, and also to make the changeover
gradually in a stepwise fashion, replacing each dose, or even
half dose, one at a time over perhaps weekly intervals.
Withdrawal can then proceed as for diazepam with small
decrements of 0.5–1mg at a time, decrements that are not easily
achievable with other benzodiazepines. The same technique can be
used for Klonopin. I know that some patients report that they
find this difficult, but I suspect it is because the changeover
is not carried out carefully enough, with due regard to
potencies and individual differences.
I should add that some benzodiazepines are available in liquid
form and it is possible to withdraw from these directly,
reducing dosage millilitre by millilitre or drop by drop.
What about adjuvant drugs? Are there any drugs that help to
cushion the withdrawal process? The short answer is no: any drug
that substitutes for benzodiazepines is benzodiazepine-like
itself. However, several drugs have been tried, though none have
proved generally useful.
Adjuvant Drugs In Benzodiazepine Withdrawal
Slide 16
Antidepressant drugs may be indicated if depression is severe,
and anyone already on an antidepressant should continue it until
after the benzodiazepine has been withdrawn. Antidepressants,
including SSRIs, have been shown to have anxiolytic effects and
may be indicated as longer-term treatment for chronic anxiety
disorders. Small doses of sedative antidepressants can be
helpful for insomnia. But all antidepressants, as I mentioned
yesterday, also produce withdrawal effects when stopped.
B blockers may help tremor and palpitations as a temporary
measure. Carbamazepine and other anticonvulsants prevent fits
during withdrawal from high doses of benzodiazepines. Sedative
antihistamines such as Phenergan may help with sleep but should
not be used long-term.
Bispirone, clonidine, and nifedipine have all been shown to be
unhelpful. Gabapentin has been claimed to be beneficial but
there are no controlled trials. The benzodiazepine receptor
antagonist flumazenil (Romazicon) was effective in some trials
but has to be given intravenously and repeatedly and it can
actually precipitate reactions.
None of these drugs (except possibly antidepressants) should be
necessary for people on therapeutic doses withdrawing slowly
enough.
SLIDE 15 Again
Slide 15
What about psychological support? Many people require little
more than simple and repeated encouragement and proper
information. Self-support groups can be a great help for many.
Some may need more formal psychological therapies including
anxiety management, stress-coping strategies and cognitive
behavioural therapy. Support when needed should be available
both during and after withdrawal. Some patients may remain
vulnerable to stress for some months.
In general practice settings, even minimal information can be
effective. In one general practice study of elderly patients on
long-term hypnotics, a single letter advising them to try
reducing by half a tablet every few weeks resulted in
significant dose reduction or complete withdrawal within six
months, with improvement in mental and physical health and no
withdrawal symptoms or sleep problems. Another general practice
study of withdrawal in elderly hypnotic users using placebo
tablets found that 80% had withdrawn in six months with no sleep
or withdrawal problems and significant improvement in cognitive
performance.
Of course patients have to be motivated to withdraw—it is no use
forcing withdrawal on reluctant patients. But a single medical
consultation explaining the risks of long-term benzodiazepine
use, or even media publicity can help to motivate people.
[move][font=courier]Finally, what can we do to halt
overprescription of benzodiazepines in the future and to prevent
yet more people getting caught in the so-called tranquilliser
trap?
[/font][/move]
Slide 17
Steps Needed to Reduce Benzodiazepine Overprescribing
Some Steps Needed to Reduce Benzodiazepine Overprescribing
Slide 18
Prof. Ashton's speaking notes did not include Slide 18 but the
PowerPoint® presentation did. So we have included the slide
here, as it obviously flows from Slide 17.
Copyright © Prof. C. Heather Ashton, DM, FRCP, Emeritus
Professor of Clinical Psycho-Pharmacology at the University of
Newcastle upon Tyne, England.
www.psychmedaware.org/HistoryBenzodiazepines.html
Updated October 31, 2012
About PMAG
Dr. Ashton
— Conditions of Use | Privacy | Disclaimer | Search &
Navigation | Site Map —
© 2005–2014 Psychiatric Medication Awareness Group. No part of
this site
Agelbert NOTE: links to slides at link: 8)
HTML http://www.psychmedaware.org/HistoryBenzodiazepines.html
#Post#: 3187--------------------------------------------------
Re: DRUGS - HISTORY - USE AND ABUSE - DOCTOR AND PATIENT MISTAKE
S
By: AGelbert Date: May 21, 2015, 7:04 pm
---------------------------------------------------------
[quote]
About Carl Hart
According to neuroscientist and drug abuse specialist Carl Hart,
most of what we have been told about drugs and addiction is
wrong. Growing up in an impoverished and predominantly
African-American neighborhood of Miami, Carl witnessed and
experienced the multitude of factors that lead to addiction. A
“combination of choice and chance” led him to leave his
community and attend college, starting Carl on a path that
culminated in his appointment as the first African-American
tenured professor of the sciences at Columbia University. His
scientific research and personal experiences have informed the
thrust of Carl’s book The High Price — that addiction is less
prevalent and problematic than we have been led to believe, and
that drugs have been scapegoated for problems related to poverty
and race.
HTML http://tedmed.com/talks/show?id=309156
About This Talk
Carl Hart
HTML http://www.pic4ever.com/images/19.gif,
Associate
Professor of Psychiatry and Psychology at Columbia University,
offers a provocative, evidence-based view of addiction and
discusses how it should impact drug policy.[/quote]
HTML https://www.youtube.com/watch?v=C9HMifCoSko&feature=player_embedded
[move]Eighty to ninety PERCENT of the people who use illegal
drugs are NOT ADDICTS and DON'T HAVE A DRUG PROBLEM! [/move]
#Post#: 12682--------------------------------------------------
China forcefully harvests organs from detainees, tribunal conclu
des
By: Surly1 Date: June 22, 2019, 7:19 am
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China forcefully harvests organs from detainees, tribunal
concludes
HTML https://www.nbcnews.com/news/world/china-forcefully-harvests-organs-detainees-tribunal-concludes-n1018646?fbclid=IwAR2tfKOYJR-ji-1cbAfe5ijItVhR4_2NU91F-c0pkQ1dP1s5xg9TIpRJX84
Organ transplant trade is worth $1 billion a year.
[img
width=800]
HTML https://media3.s-nbcnews.com/j/newscms/2019_25/2900231/190618-china-transplant-mc-1416_de3792c5a533ccf72f3a7174d452b6df.fit-2000w.JPG[/img]
Chinese doctors perform a kidney transplant operation at the
Second Xiangya Hospital of the Central South University in
Changsha city, Hunan province.Fu zhiyong / Fu zhiyong -
Imaginechina
[html]<section class="mb7"> <div class="mb1 founders-mono f2
lh-copy gray-80 ls-tight"><time class="relative z-1"
datetime="Tue Jun 18 2019 13:47:00 GMT+0000 (UTC)"
data-test="timestamp__datePublished" itemprop="datePublished"
content="2019-06-18T13:47:00.000Z">June 18, 2019, 9:47 AM
EDT</time></div> <div class="founders-cond f6 lh-none"
data-test="byline">By Saphora
Smith</div> </section> <div
class="bodyContent___1eruQ"> <p
class="endmarkEnabled">LONDON — The organs of members of
marginalized groups detained in Chinese prison camps are being
forcefully harvested — sometimes when patients are still
alive, an <a href="
HTML https://chinatribunal.com/about-etac/"<br
/>target="_blank" rel="noopener">international tribunal</a>
sitting in London has concluded.</p> <p
class="endmarkEnabled">Some of the more than 1.5 million
detainees in Chinese prison camps are being killed for their
organs to serve a booming transplant trade that is worth some $1
billion a year, concluded the China Tribunal, an independent
body tasked with investigating organ harvesting from prisoners
of conscience in the <a
href="
HTML http://www.eiu.com/Handlers/WhitepaperHandler.ashx?fi=Democracy_Index_2018.pdf&mode=wp&campaignid=Democracy2018"<br
/>target="_blank" rel="noopener">authoritarian
</a>state.</p> <div id="taboolaReadMoreBelow"></div> <p
class="endmarkEnabled">“Forced organ harvesting has been
committed for years throughout China on a significant
scale,” the tribunal concluded in its <a
href="
HTML https://chinatribunal.com/wp-content/uploads/2019/06/Short-Form-Conclusion-China-Tribunal.pdf"<br
/>target="_blank" rel="noopener">final judgment Monday.</a> The
practice is “of unmatched wickedness — on a death
for death basis — with the killings by mass crimes
committed in the last century,” it added.</p> <p
class="endmarkEnabled">In 2014, state media reported that <a
href="
HTML http://www.nbcnews.com/id/46849651/ns/world_news-asia_pacific/t/china-phase-out-prisoner-organ-donation/#.XQjdq_lKi9I"<br
/>target="_blank" class=" vilynx_listened" rel="noopener">China
would phase out the practice</a> of taking organs from executed
prisoners and said it would rely instead on a national organ
donation system.</p> <p class="endmarkEnabled">The Chinese
Ministry of Foreign Affairs on Tuesday was not immediately
available to comment on the tribunal's findings.</p> <p
class="endmarkEnabled">In a statement released alongside the
final judgment, the tribunal said many of those affected were
practitioners of Falun Gong, a spiritual discipline that China
banned in the 1990s and has called<a
href="
HTML https://www.economist.com/the-economist-explains/2018/09/05/what-is-falun-gong"<br
/>target="_blank" rel="noopener"> an “evil cult.”</a
>
The tribunal added that it was possible that Uighur Muslims
— an ethnic minority who are currently being detained in
vast numbers in western China — were also being
targeted.</p> <p class="endmarkEnabled">The tribunal is
chaired by Sir Geoffrey Nice, who worked as a prosecutor at the
international tribunal for crimes committed in the former
Yugoslavia.</p> <p class="endmarkEnabled">“Falun Gong
practitioners have been one — and probably the main
— source of organ supply,” the judgment read, while
“the concerted persecution and medical testing of the
Uyghurs is more recent,” using a different spelling of the
minority group's name. It warned, however, that the scale of
medical testing of the Uighur Muslims meant they could end up
being used as an "organ bank."</p> <p
class="endmarkEnabled">The tribunal that delivered its judgment
in London was initiated by the International Coalition to End
Transplant Abuse in China — a not-for-profit coalition
including lawyers, academics, human rights advocates and medical
professionals.</p> <p class="endmarkEnabled">Allegations of
forced organ harvesting first came to light in 2001, after a
boom in transplant activity was registered in China, with wait
times becoming unusually short, the statement said. Chinese
websites advertised hearts, lungs and kidneys for sale and
available to book in advance, suggesting that the victims were
killed on demand, it added.</p> <p class="endmarkEnabled">On
Monday, the tribunal concluded that there was “numerical
evidence” of the “impossibility of there being
anything like sufficient ‘eligible donors’ under the
recently formed PRC [People’s Republic of China]
voluntary donor scheme for that number of transplant
operations.”</p> <p class="endmarkEnabled">The
tribunal added that witnesses, experts and investigators had
told of how Falun Gong practitioners continued to be killed in
order for their organs to be extracted. It added that forced
organ harvesting was also being performed while victims are
still alive, killing the person in the process.</p> <p
class="endmarkEnabled">The statement recalled how one witness,
Dr. Enver Tohti, told of how as a surgeon in China he had been
required to perform organ extractions. Referring to one instance
in which he extracted an organ from a living patient, he said:
“What I recall is with my scalpel, I tried to cut into his
skin, there was blood to be seen. That indicates that the heart
was still beating … At the same time, he was trying to
resist my insertion, but he was too weak.”</p> <p
class="endmarkEnabled">Several survivors of prison camps told
the tribunal of how they were subjected to physical examinations
including blood tests, X-rays and ultrasounds, the statement
said. “Experts report that the only reasonable explanation
for these examinations was to ensure that victims’ organs
were healthy and fit for transplantation,” it added. A
healthy liver, for example, can reportedly be sold for some
$160,000, according to the statement.</p> <p
class="endmarkEnabled">The tribunal concluded that it was
"beyond reasonable doubt" that crimes against humanity had been
committed against the Falun Gong and Uighur Muslims but that it
could not prove that the killing of the Falun Gong amounted to
genocide — because of the tribunal's inability to prove
‘intent’ to commit
‘genocide.’</p> <p class="endmarkEnabled">In a
statement accompanying the final judgment, the International
Coalition to End Transplant Abuse in China called on the
international community to help bring an end to forced organ
extraction.</p> <p class="endmarkEnabled">“It is no
longer a question of whether organ harvesting in China is
happening, that dialogue is well and truly over. We need an
urgent response to save these people’s lives,” Susie
Hughes, executive director and co-founder of the coalition,
said.</p> <p class="endmarkEnabled"><em>Saphora Smith
reported from London. Dawn Liu and Ed Flanagan reported from
Beijing. </em></p> </div>[/html]
#Post#: 12684--------------------------------------------------
China forcefully harvests organs from detainees, tribunal conclu
des
By: AGelbert Date: June 22, 2019, 1:03 pm
---------------------------------------------------------
[center]It is no longer a question of whether organ harvesting
in China is happening
HTML http://renewablerevolution.createaforum.com/advances-in-health-care/drugs-history-use-and-abuse-doctor-and-patient-mistakes/msg12682/#msg12682[/center]
:o That's pretty ugly stuff going on over there. :(
I have read over the years that this heinous organ harvesting
practice began in Israel (using Palestinian prisoners), then
spread to other places like India (there they at least pay poor
people to sell organs to get money for bridal dowries),
Singapore, China and so on.
There are those that claim it is quite common in the USA too. I
would not doubt it, considering how corporations here have taken
over the Prison Industrial Complex. If the only criteria in
Fascist Merika for deciding whether to do something or not is
whether you can make money from it, then it becomes the
"fiduciary duty" of Prison corporations to harvest organs from a
young prisoner that "accidentally died in a fight with another
prisoner". Hey, somebody has to pay for that funeral, right?
I could call this another example of a "moral hazard" in
Capitalist business practices, but I shouldn't do that because
that would imply that corporate decision makers view gross
immorality for profit as a hazard rather than a virtue. Now you
know why our police mostly lock up healthy young poor people.
[center][img
width=340]
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