Overload

Benzodiazepines

Category: Medicines

Type

Involuntary

Introduction and description

Benzodiazepines are classified as anxiolytic (anti-anxiety), sedative, hypnotic, anticonvulsant, and muscle relaxant as well as amnesic. 

They were only intended ever to be used pharmaceutically on an infrequent one off basis to treat anxiety, agitation, seizures, muscle spasms and as a premedication for medical or dental procedures. They are also used in the longer term care of the dying. 

There are around about  35 benzodiazepines which are currently used medically.

Benzodiazepines do not have any pain relieving properties of themselves, however, they can be used on a one off basis for their muscle relaxant properties to alleviate pain which is caused by muscle spasms, if used longer term, tolerance develops to the muscle relaxant effects.

They are only used to provide a one off treatment for seizures, and should never be prescribed for long term treatment.  The reason is that on any long term basis, tolerance develops and any abrupt or even managed withdrawal of the drug can cause severe life threatening seizures.  Benzodiazepines should never be used for the long-term management of epilepsy.

One of the strangest facets of benzodiazepine medication, is that they are sometimes prescribed for insomnia.  This is actually misprescribing.  While benzodiazepines induce sleep, they tend to produce a poorer quality sleep than natural sleep. Benzodiazepines suppress REM sleep,  disrupting or interfering with the brain's delta waves. Delta waves signify the brain's slowest waves (~4 Hz) and occur during Stage 4 sleep, which represents humans' deepest sleep state (our muscles are the most relaxed; breathing slows and becomes shallow), and the stage right before R.E.M. sleep and dreaming (Stage 5). Therefore, upon waking, this disruption of Stage 4 delta wave sleep causes a failure for an adequate brain/body rest or "recharge". If we summarise this, they actually are no help at all, in fact very counter-productive.

 

Another mis-use – mis-prescription in other words - is their use to treat alcoholism!  Benzodiazepines, according to the literature, have  been used “for the treatment and prevention of alcohol withdrawal syndrome”.  I found this extraordinary - I must admit I did think – well off one drug and onto another – and onto another class which is hugely addictive - more addictive than ever alcohol is.  They do have the advantage over alcohol in that they don’t destroy your liver “impaired liver function is not a hazard with these drugs  since they  do  not require oxidation, hepatic or otherwise, for their metabolism”.  That must be a great relief to those struggling with their addictive effects – ‘well I may be suffering from depression, life threatening seizures, tremors, headaches and  insomnia but at least my liver is OK!!’

It may be worth adding that urgent action by national governments has been recommended by a large number of patient groups, to improve the prescribing patterns of benzodiazepines.  There is also widespread condemnation of the marketing used for some of the drugs, both in the past and now
See below the page for a classic demonstration of this………….



1987 Ativan advertisement. "In a
world where certainties are few...
no wonder Ativan is prescribed
by so many caring clinicians


Early lorazepam marketing, a 1977
direct-to-patient advertisement
implying its positive effects:
"Now it can be yours - The Ativan
Experience [both from Wikipedia]

Mis-use and abuse

A large-scale, nationwide, U.S. government study of pharmaceutical-related Emergency department visits found that sedative-hypnotics in the United States are the pharmaceuticals most frequently used outside of their prescribed medical purpose, with 35% of drug-related emergency room visits involving sedative-hypnotics. In this category, benzodiazepines are the most commonly used.

Benzodiazepines are more commonly abused than opiate pharmaceuticals, which account for 32% of visits to the emergency department. No other pharmaceutical is more commonly abused than benzodiazepines.

Males and females use benzodiazepines for non medical purposes equally. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drug, with 26% of attempted suicides involving benzodiazepines.

Benzodiazepines account for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines.  In Northern Ireland in cases where drugs were found in tests on impaired drivers, benzodiazepines were found to be present in 87% of cases.  In Norway benzodiazepines are the most commonly detected illicit drug in suspected drugged drivers being detected in 38-57 percent of drivers.

Of course the million dollar question is why?  And the million dollar answer is because it can on a very temporary basis create complete release from anxiety,  relaxation of a quite profound sort.  In the section on suppression actions I have described techniques that can be used to promote total relaxation without the use of drugs, but some people seem unable to use these techniques, do not have the time or patience to persevere with them or do not know about them.  Thus, although using benzodiazepines does not  strictly speaking give you a spiritual experience, for many people it is very close to one, because they live their lives in a state of nervous energy, turmoil, racing thoughts, terrible anxiety and tension, tension, tension.  And suddenly they find calm – peace.  And for them it is heaven.

It is also worth noting that these drugs are often used in combination with LSD, or other ‘challenging’ drugs, because ‘it reduces the fear and tension in using them’!! [Give me strength]

Tolerance, dependence and addiction

 

All benzodiazepine drugs cause tolerance, physical dependence and addiction. Dose increases may overcome the effects of tolerance, however, tolerance gradually returns.  The higher the dose and the longer the drug is taken the greater the risk of experiencing hugely unpleasant withdrawal symptoms.

Benzodiazepines are not intended to be used frequently, nor on a long term basis.  In most responsible medical literature, the treatment period is given as a MAXIMUM of 2 weeks [there are some exceptions as I have already explained  related to terminal care]. In many cases, they are prescribed on the basis that they should be used extremely infrequently – as and when a real need emerges and at the prescribed dose only – which is always very low.  The absolute minimum needed to tip the balance the right way.

Tolerance to all the benzodiazepines develops very rapidly.

Withdrawal symptoms can occur from standard dosages and also after very short-term use - a matter of days and not weeks.  Withdrawal symptoms have been seen after less than seven days administration of these drugs. With prolonged use, the elimination half-life may increase up to days.

Generally speaking tolerance [tachyphylaxis] is usually caused by:

  • depletion or marked reduction of the amount of the natural endogenous GABA neurotransmitter responsible for creating the drug's effect.
  • or by the depletion of receptors available for the drug or neurotransmitter to bind to.

This latter depletion is caused by the cell's reducing the number of receptors in response to their saturation.  All benzodiazepines, bind to specific sites on the GABAA gamma-amino-butyric acid receptor. In effect, long term use either damages these receptors or permanently kills them off, meaning that long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and less powerful in their effects. 

If you then withdraw the drug, you are hit by a double whammy.  Not only have you taught the body not to emit the endogenous chemical you need [GABA], but you have also reduced the number of receptors available for what little natural chemical is still left.  A lose lose situation!!

Withdrawal symptoms

One third of individuals regularly treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience withdrawal symptoms upon dose reduction.

Some start to experience withdrawal symptoms on a steady dose maintenance as the body becomes tolerant to the drugs.  High dosage and long term use increases both the severity of dependence and withdrawal symptoms.  

Benzodiazepines are notorious for producing what are called euphemistically “Paradoxical reactions”. What this means is that your original symptoms come back with a vengeance, usually exaggerated.  If you were a little agitated before, after withdrawal you will be hyperactive, if you had muscle spasms, the seizures will be chronic or life threatening.  If you were  a bit anxious before the drug, you will be over whelmed by panic attacks and fear on withdrawal. If you were a bit unhappy before, you will become morbidly depressed.  If you had trouble sleeping before, you will become an insomniac.    If you were a little bit confrontational before you took these drugs, afterwards you will be overwhelmed with aggressive behaviour and anger.   Paradoxical reactions are particularly associated with intravenous administration. 

We can see why these reactions occur.   Not only have you taught the body not to emit the endogenous chemical you need [GABA], but you have also reduced the number of receptors available for what little natural chemical is still left.  You will be severely short of a key neurotransmitter and its effects.

Withdrawal effects include permanent cognitive impairment.  The medical literature is a little guarded about the effect here, saying that permanent impairment of memory is not proven, because of course no one can say what their memory was like before they took the drug to prove this one way or another.  Most people upon withdrawal of high or regular doses have difficulty in remembering anything much, so they are unlikely to remember what they were like several weeks or months ago.  But the case histories from those who write up their experiences, to me, prove that permanent damage is done. 

Withdrawal symptoms in general can range from:

  • Severe anxiety [far far worse than that it was intended to treat] along with tension, restlessness, confusion, irritability, extreme agitation, panic attacks.
  • Profound insomnia.
  • Severe depression.
  • Psychosis – hallucinations, visions, schizophrenic like symptoms, mania, dysphoria, derealisation, depersonalisation and so on, even delirium.
  • Suicidal tendencies.
  • Severe muscle spasms – tremors, headaches, dizziness, stomach cramps, unsteadiness, life threatening seizures.
  • Heart problems – such as palpitations, tachycardia, hypotension.
  • Problems with body temperature control – including profuse sweating and hyperthermia.
  • Nervous sensation problems – including numbness/tingling of extremities and  hypersensitivity to light, sound, and smell as well as perceptual distortions.
  • Gastrointestinal problems including - nausea, vomiting, diarrhea, appetite loss.
  • Permanent  disinhibition - sometimes accompanied by rage, excitement , agitation, hyperactivity, restlessness and impulsivity.  This can be accompanied by permanent personality and behavioural changes.
  • Permanent  sexual dysfunction – and loss of libido.

Sudden withdrawal after long-term use can cause severe, even fatal, symptoms.  Sudden withdrawal may for example induce the potentially life threatening condition status epilepticus.

Who should they not be used by?

For all the reasons we can see above, there are very clear guidelines about who should be given benzodiazepines and who should not.

All the medical literature is in agreement that they should not be given to people with ‘addictive personalities’.  Not alcoholics, not those attempting to come off drugs, not those on drugs already, compulsive obsessives, not heavy smokers – all of whom fall within this definition anyway.  Nor should they be given to people who have ‘mental problems’ – various psychoses or a history of this in the family.  Nor should they be given to anyone with “severe personality disorders, such as Borderline Personality Disorder”.

People with various illnesses caused by brain damage – Parkinsons disease, and so on are also best not given the drugs, principally because benzodiapezines react with so many other drugs given for these conditions.  For example, Diazepam blocks the action of levodopa (used in the treatment of Parkinson's Disease). 

On the whole anyone on other strong drugs or pharmaceuticals are probably best to not use benzodiazepines as the interactions can be anything from unpredictable to dangerous.  Benzodiazepines increase the central depressive effects of

  • Alcohol
  • other hypnotics/sedatives (e.g., barbiturates)
  • narcotics
  • other muscle relaxants
  • certain antidepressants
  • sedative antihistamines
  • opiates
  • antipsychotics
  • as well as anticonvulsants such as phenobarbital, phenytoin and carbamazepine.

Drugs such as Cimetidine, omeprazole, oxcarbazepine, ticlopidine, topiramate, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenecid, propranolol, imipramine, ciprofloxacin, fluoxetine and valproic acid prolong the action of diazepam by inhibiting its elimination.  Oral contraceptives  ("the pill") can sometimes significantly decrease the elimination of the metabolites of these drugs.

In the responsible medical literature, the prescribed use of all benzodiazepines is definitively not recommended for children or the young [usually defined as under 18 or under 21] and is not recommended for pregnant or nursing mothers, as it can seriously harm the baby.  The exception to this rule is that they have a place when the person is dying.

 

Again, in the responsible medical literature, the prescribed use of all benzodiazepines is definitively not recommended in the elderly

And again, the exception to this rule is that they have a place when the person is dying.  Despite this very clear medical advice, they are given quite frequently to the elderly, as a sedative on a regular basis in care homes,  a group, who are at particular risk from ‘overdose’.  One very good reason why benzodiazepines should never be given to the elderly is that they impair body balance and standing steadiness; they are directly responsible for many falls and hip fractures in this vulnerable group.  I found a number of examples of the elderly whose [unwanted] hallucinations were not caused by brain damage or dementia, as thought, but by these prescription drugs.

Furthermore, these should not be used by those with low blood pressure, or heart problems or any form of thyroid problems.    They should also not be used by people with eye problems such as glaucoma.

Benzodiazepines  depress central nervous system respiratory drive and are “contraindicated in severe respiratory failure”, for example bronchitis or lung diseases. An example of dangerous mis-use would be to relieve anxiety associated with acute severe asthma.  They can also cause problems with those who suffer sleep apnea  “Patients with severe attacks of apnea during sleep may suffer respiratory depression leading to respiratory arrest and death”.  They can be fatal if used with opiates, which also  cause severe respiratory depression.

Overdose

Benzodiazepine overdose causes excess central nervous system (CNS) depression and may include one or more of the following symptoms: 

  • Somnolence (sleepy state)
  • Hypotension (low blood pressure)
  • Hypoventilation (shallow breathing) respiratory depression
  • Impaired motor functions , dizziness and impaired balance
  • Muscle weakness
  • Impaired or absent reflexes
  • Fainting
  • Coma
  • Death

The antidote for an overdose of a benzodiazepine is flumazenil (Anexate), which is a GABA antagonist. This drug is only used in cases with severe respiratory depression or cardiovascular complications. The reason that flumazenil is infrequently used is that it can trigger seizures in mixed overdoses and in benzodiazepine dependent individuals.  In these cases,  activated charcoal is used for ‘decontamination’ of the stomach following an overdose.

Because flumazenil is a short-acting drug, and the effects of benzodiazepines can last for days, several doses of flumazenil may be necessary. Artificial respiration and stabilization of cardiovascular functions may also be necessary.

Overdoses of benzodiazepines with alcohol, opiates and/or other depressants can be fatal.

There have been fifteen epidemiologic studies which have shown that prolonged hypnotic drug use is associated with increased mortality, and this is partly due to increased cancer deaths. “The  likelihood of cancer causation is sufficiently strong now that physicians and patients should be warned that hypnotics possibly place patients at higher risk for cancer".

Side effects

The immediate effects of taking a benzodiazepine, as oppose to the longer term effects, are similar in all the benzodiazepines and include: 

  • pupil dilation - which  - if you have any eye problems such as  narrow-angle glaucoma – can be serious
  • Nausea and excess flatulence, constipation, urinary retention
  • Drowsiness, dizziness, lightheadedness, fatigue, unsteadiness and impaired coordination, vertigo - One Australian study has found that “people who take sleeping pills or anti-anxiety medications are more dangerous on the roads than drunk drivers
  • Skin rash, hives, vitiligo, psoriasis
  • Dry mouth (infrequent)
  • Ataxia and slurred speech
  • Twitches and tremor
  • Disinhibition – sometimes accompanied by rage, excitement , agitation, hyperactivity, restlessness and impulsivity
  • Euphoria or severe dysphoria
  • Loss of libido
  • Impaired motor function  - impaired coordination ;  impaired balance, and dizziness
  • Serious psychological and psychiatric side-effects including hallucinations but also ‘suicidal ideation’, mania and depression
  • Serious interference with cognitive performance - short-term memory loss; anterograde amnesia (common with higher doses), confusion.  For example “Five participants in a sleep study were prescribed lorazepam 4 mg at night, and the next evening three subjects unexpectedly volunteered memory gaps for parts of that day
  • Thrombocytopenia  - a relative decrease of platelets in blood.
  • Induction of seizures
  • Respiratory depression
  • Hypotension

 There is one side effect rarely mentioned or given much space in medical literature and yet it is in many ways one of the more serious and that is having taken these drugs, you don’t care a toss about anything – your work, other people, what people think about you or that you are totally unfit to drive or do anything.  You are in the least worse case a liability, in the worst case a danger to yourself and others.  The medical text books sometimes call this a  ‘lack of motivation’, but this rather underestimates the seriousness of what can happen.  For example:

Sweeping Calmness - Alprazolam (Xanax) - by Anonymous [edited for brevity]
I've recently begun to have problems with anxiety attacks in addition to depression.
One morning before I left for work I noticed the usual symptoms of an oncoming attack…. I decided to look through our medicine cabinet to see if we had something, anything to get me through it.
I came upon a nearly full bottle of Xanax, and took a .25 mg dose at 7:45 a.m. … At 30 minutes I was extremely calm and the symptoms of the attack were gone. Once I arrived at work I found it was somewhat difficult to concentrate…... I also noticed that I was speaking more slowly than usual, but I was too relaxed to try to sound normal.
Around 10 a.m. I was getting pretty lethargic, but I was completely enjoying it. I wanted nothing more than to just sit at my desk and stare out the window. This relaxed state lasted throughout the day, and I went home and slept the best night's sleep I had had in 3 months.
It is definitely a good drug to help with anxiety/stress/sleeping trouble, but I wouldn't recommend taking it before driving.

Oh dear!!  I hope I don’t have her dealing with my problems when I ring up the gas leak or the car accident I have just witnessed, or the sneaky looking man with a bomb strapped to his back entering the White House.

Deaths

Using the figures from eHealthme compiled from doctor submitted Adverse Drug reports to the FDA and SEDA, we have provided a section covering deaths [the ultimate spiritual experience]  - see Benzodiazepines deaths

As of August 2015, the total came to 8,462

This figure only applies to the US and thus excludes all deaths caused by these drugs in the rest of the world.  Furthermore, because of the repeated rebranding and renaming of drugs, the figure will exclude many drugs which have not been captured by eHealthme because of the numerous names in operation.

How it works

Benzodiazepines can give you hallucinations, visions, near death experiences, the occasional out of body experience and the ultimate experience - death! 

Physically and theoretically, all Benzodiazepines enhance the effect of the neurotransmitter GABAA receptor.  They are GABA-A receptor ‘enhanced’ agonists, that is they cause an enhanced binding of GABA (gamma-aminobutyric acid) to GABAA receptors. GABA is a major inhibitory neurotransmitter in the brain, involved in inducing sleepiness, muscular relaxation and control of anxiety and seizures.

So much for the theory.

Functionally however, benzodiazepines are regarded by the system as a threat

They mimic an endogenous chemical that is used by the body to regulate our activity and the Will sees the chemical as a threat to its regulatory system.  It knows it is not the chemical GABA, it knows that it is mimicking GABA as such it is a special sort of virus and one which will require all its resources to combat.

So it starts to shut down functions in order to combat the effects.

And gradually this is exactly what it does.    Learning, and  reasoning, and  memory,  all get suppressed first and indeed once suppressed the composer can come through. 

But by then we may never remember the experience because memory has gone.

This is the only time that spiritual experience is likely unless, later on you get a near death experience.

Emotion often stays unsuppressed for some time, which is why people on benzodiazepines can become uncontrollably angry, or lustful, or sad depending on the emotion that was prevalent at the time the drug was taken.

If things have become serious then emotion shuts down, then the nervous system gets slowed down, then the 5 senses start to go and eventually we go into a coma.

The diagram below shows the end result.  Total suppression, the composer can get through, but it will have no effect because we are no longer at home.  If you do not believe me then please read the following Observations

002197 – Two shots in the head
002198 – Addiction and misery
002203 – Temazepam amnesia
002204 – 17 lost years

Which are graphic accounts of the effects of benzodiazepines in which there was no spiritual experience, but all the above took place.

Observations

There are a lot of drugs that are in this section – a lot. 

All of them have caused hallucinations and the number of hallucinations caused is extremely impressive – thousands upon thousands.  Remember that the number in brackets after the drug is an indicator of the number of unwanted hallucinations that have been recorded by the eHealthme web site and compiled from SEDA and FDA figures.  Some, perhaps many, of these may have been near death experiences – we will never know.  The links take you to the eHealthme web site where an up-to-date page for the side-effects can be found.

Many of the drugs are used ‘recreationally’ and because of this I have been able to include links to EROWID.  But reading the observations I cannot understand why.  If you follow them they make very sobering reading.  

Observation identifiers

Observation name

No of observations

002166

Vietnam perfect recall

1

002167

Trip to outer space

1

002168

Ativan in the elderly

1

002194

Alprazolam and Xanax

903

002195

Alprazolam zombie

0

002196

Clonazepam and Klonopin

1290

002197

Two shots to the head

0

002198

Addiction and misery

0

002199

Diazepam and Valium

547

002200

Diazepam shakes and brain damage

1

002201

Temazepam and Restoril, Normison

124

002202

Lorazepam and Ativan

1421

002203

Temazepam amnesia

0

002204

17 lost years

0

002205

Versed and Midazolam

31

002206

Hospital patients

5

002207

Oxazepam

34

002208

Halcion and Triazolam

71

002209

Librium and Chlordiazepoxide/ Libritabs

17

002210

Tranxene and Clorazepate

38

002211

Dalmane and Flurazepam

7

 

Estazolam, brand names ProSom, Eurodin

9

002212

Prazepam   various trade names: Centrac, Centrax, Demetrin, Lysanxia, Mono Demetrin, Pozapam, Prasepine, Prazene, Reapam and Trepidan etc etc

2

-

 Quazepam (marketed under brand names Doral, Dormalin)

-

 

TOTAL

4503

 

Miscellaneous drugs

 The following drugs either have no figures on the eHealthme web site, but a record on EROWID. 

  • Nitrazepam is  marketed in English-speaking countries under the brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos, and Somnite.  Nitrazepam is very rarely prescribed, but is still taken in overdose by drug abusers or suicidal individuals, sometimes leading to death. Nitrazepam is “a popular drug of abuse in countries where it is available”. For example, Nitrazepam was the most commonly detected benzodiazepine in urine samples in the UK in 1997 suggesting a high liking and preference amongst drug abusers.  In India up to 50-60% of heroin addicts abuse benzodiazepines and 20% of injecting substance misusers also inject benzodiazepines.  The System of Objectified Judgement Analysis for assessing whether drugs should be included in drug formularies based on clinical efficacy found that “nitrazepam is unsuitable to be included in drug prescribing formularies”. 
  • Bromazepam  - marketed under several brand names, including Lectopam, Lexotan, Lexilium, Lexaurin, Brazepam, Bromaze, and Lexotanil  is a benzodiazepine derivative drug, developed in the 1970s. This gives the EROWID link 
  • Flunitrazepam  other names Rohypnol; Hypnodorm; Narcozep; Ruffies; Roofies; -  is marketed as a potent benzodiazepine derivative.  Not many experiences .  This gives the EROWID link 
  • Nimetazepam  - marketed under brand name Erimin is a benzodiazepine derivative. No experiences.  This gives the EROWID link
  • Tetrazepam, (is marketed under the following brand names, Clinoxan, Epsipam, Myolastan, Musaril, Relaxam and Spasmorelax) is a benzodiazepine derivative with anticonvulsant, anxiolytic, hypnotic and muscle relaxant properties. It is used mainly in to treat muscle spasm, anxiety disorders such as panic attacks, or more rarely to treat depression, premenstrual syndrome or agoraphobia. Tetrazepam has relatively little sedative effect at low doses while still producing useful muscle relaxation and anxiety relief.  It is rarely abused because it has ‘no mind numbing effects!’

Related observations