Plurk paste

1. WHAT IS A BENZODIAZEPINE?

什麼是苯二氮平？

Benzodiazepines are a large class of commonly prescribed tranquillisers,

BZD是一種常見的處方用鎮定劑
otherwise referred to as central nervous system (CNS) depressants, anxiolytics and sedative-hypnotics.

就是常講的抗焦慮藥(CNS)，鎮靜安眠藥

They include
包括了
alprazolam (Xanax),
贊安諾
bromazepam (Lexotan, Lexomil),
chlordiazepoxide (Librium, Nova-Pam),
clonazepam (Klonopin, Rivotril),
氯硝西泮 (利福全 / 克癲平)
clorazepate (Tranxene),
diazepam (Valium, D-Pam, Pro-Pam),
丹騎平、煩寧
estazolam (ProSom),
flunitrazepam (Rohypnol),
flurazepam (Dalmane),
當眠多、大饅頭
halazepam (Paxipam),
ketazolam (Anxon),
loprazolam (Dormonoct),
lorazepam (Ativan),
羅拉泮、羅拉西泮、勞拉西泮(安定、安定文)
lormetazepam (Noctamid),
medazepam (Nobrium),
midazolam, (Versed, Hypnovel, Dormicum),
nitrazepam (Mogadon, Insoma, Nitrados),
oxazepam (Serax, Serapax, Serenid, Benzotran),

心益
prazepam (Centrax),
quazepam (Doral),
temazepam (Restoril, Euhypnos, Normison, Sompam),

(悠樂丁)
triazolam (Halcion, Hypam, Tricam).
三倫(酣樂欣)

See: Benzodiazepine Drug Index for links to monograph and drug information sites.

Some lesser known benzodiazepines:
brotizolam, camazepam, clotiazepam, cloxazolam,
delorazepam, etizolam, fludiazepam, haloxazolam,
oxazolam, nimetazepam, nordazepam, pinazepam, tetrazepam, tofisopam.

較罕見的BZD
See: Benzodiazepine Drug Index.

All benzodiazepines have five primary effects. They are:

所有BZD都有五種主要的效果
1. Hypnotic (tending to make you sleepy);

催眠

2. Anxiolytic (tending to reduce anxiety/produce relaxation);

抗焦慮
3. Anti-seizure (tending to reduce the probability of having seizures and convulsions);

抗痙攣
4. Muscle relaxant (tending to reduce muscle tension and associated pain);

肌肉鬆弛
5. Amnesic (amnestic) (tending to disrupt both long and short term memory).

失憶
There may be secondary effects as well. Different benzodiazepines exhibit these primary effects to varying degrees.

不同的BZD，功能略有不同

For example, diazepam (Valium) is a relatively powerful hypnotic (sleep inducer),

像丹祈屏，對於睡眠特別有效
whereas the more modern benzodiazepines such as
alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin)
are less powerful hypnotics, but are very powerful anxiolytics.
Do not assume that because one benzodiazepine makes you sleepier than another that
this benzodiazepine is more potent than those which do not produce sleepiness
to the same degree. Often, the reverse is true.

而更新型的BZD像贊安諾、(安定文 / 安定)、氯硝西泮(利福全)
對於失眠則效果略差，但對於抗焦慮效果較強

別以為某種BZD，會更好入眠或搞到失眠
效果相近而已。反之亦然

Benzodiazepines have been referred to as being part of a larger class
of drugs known as "minor tranquillisers".

BZD原為諸多鎮靜劑的一種(以前常用巴比妥)，現在一提到鎮靜藥物，多指BZD

As applied to benzodiazepines, this is almost certainly a misnomer, and the label has fallen into relative disuse in the past ten years. However, you may encounter this term from time to time.

最近10年已逐漸停用
但是...你也可以算算看，10年已經可以用掉多少了

Benzodiazepines are most commonly prescribed for anxiety conditions, especially panic disorder (PD) and generalised anxiety disorder (GAD). They are also sometimes prescribed for seizure disorders. Klonopin, for example, is often prescribed for epilepsy.

BZD是最常見的焦慮藥方
尤其是驚恐、和各式焦慮
有時也會給癲癇患者吃利福全
就像說，開給癲癇的人吃

Benzodiazepines are also prescribed for insomnia and other sleep problems, such as restless leg syndrome (RLS).

BZD也常用於失眠、或其他睡眠問題，像情緒不穩症

Benzodiazepines are also frequently prescribed as muscle relaxants.

BZD也常用在肌肉放鬆

By far the most common benzodiazepines prescribed today are Valium, Xanax, Ativan and Klonopin. Valium (diazepam) is particularly common in the UK. Valium has become less common in the United States over the past 15 years, while Xanax and Klonopin have experienced increased popularity in the United States over this time. In certain Latin American countries, it appears that the drug Lexotan (bromazepam) is very popular.

至今，最常用到的BZD，是煩寧(丹祈屏)、贊安諾、安定文、利福全
丹祈屏在英國廣泛使用
在美國，已經快15年，少用丹祈屏
反而是贊安諾和利福全，越來越受歡迎
也常出現立舒

All benzodiazepines can cause physical dependency, otherwise commonly known as addiction.

所有的BZD都會出現生理依存症
簡單說就是成癮

2. HOW DO BENZODIAZEPINES AFFECT YOUR BODY?

BZD生理原理？

Benzodiazepines are general central nervous system (CNS)
depressants. They are all very similar chemically.
All benzodiazepines act by enhancing the actions of a natural brain chemical,
GABA (gamma-aminobutyric acid). GABA is a neurotransmitter,
an agent which transmits messages from one brain cell (neuron) to another.
The message that GABA transmits is an inhibitory one:
it tells the neurons that it contacts to slow down or stop firing.
Since about 40% of the millions of neurons all over the brain respond to GABA,
this means that GABA has a general quietening influence on the brain:
it is in some ways the body's natural hypnotic and tranquilliser.
This natural action of GABA is augmented by benzodiazepines which
thus exert an extra (often excessive) inhibitory influence on neurons.

The way in which GABA sends its inhibitory message is by a clever electronic device. Its reaction with special sites (GABA-receptors) on the outside of the receiving neuron opens a channel, allowing negatively charged particles (chloride ions) to pass to the inside of the neuron. These negative ions "supercharge" the neuron making it less responsive to other neurotransmitters which would normally excite it. Benzodiazepines also react at their own special sites (benzodiazepine receptors), situated actually on the GABA-receptor. Combination of a benzodiazepine at this site acts as a booster to the actions of GABA, allowing more chloride ions to enter the neuron, making it even more resistant to excitation. Various subtypes of benzodiazepine receptors have slightly different actions. One subtype (alpha 1) is responsible for sedative effects, another (alpha 2) for anti-anxiety effects, and both alpha 1 and alpha 2, as well as alpha 5, for anticonvulsant effects. All benzodiazepines combine, to a greater or lesser extent, with all these subtypes and all enhance GABA activity in the brain.

As a consequence of the enhancement of GABA's inhibitory activity caused by benzodiazepines, the brain's output of excitatory neurotransmitters, including norepinephrine (noradrenaline), serotonin, acetyl choline and dopamine, is reduced. Such excitatory neurotransmitters are necessary for normal alertness, memory, muscle tone and co-ordination, emotional responses, endocrine gland secretions, heart rate and blood pressure control and a host of other functions, all of which may be impaired by benzodiazepines. Other benzodiazepine receptors, not linked to GABA, are present in the kidney, colon, blood cells and adrenal cortex and these may also be affected by some benzodiazepines. These direct and indirect actions are responsible for the well-known adverse effects of dosage with benzodiazepines.

Contrary to a popular misconception, benzodiazepines do not actually increase the organic synthesis of GABA. As stated, they enhance the action of existing GABA. Actually, benzodiazepines can, over time, decrease the synthesis of GABA in certain areas of the brain. This is one of numerous theories attempting to explain the occurrence of "paradoxical" symptoms (see below).

3. HOW QUICKLY CAN I BECOME ADDICTED TO A BENZODIAZEPINE?

The time it takes to form a physical dependency on a given benzodiazepine varies widely. The following variables may play a role: the size of your dose, the regularity with which you consume your dose, and most importantly, your personal body chemistry. People have been known to form dependencies in as little as 14 days of regular use at therapeutic dose levels. Your probability of forming some degree of dependency is significant, probably at least 50%, by the time you have been using them daily for 6 months. After a year of continuous use, it is highly likely that you have formed a dependency. It is unclear whether certain benzodiazepines are associated with a more rapid onset of dependency than others.

4. WHAT ARE THE DOSE EQUIVALENCIES AMONGST VARIOUS BENZODIAZEPINES?

There are no clearly definitive equivalencies for various benzodiazepines. This author has personally seen at least a dozen different benzodiazepine equivalency charts and no two are alike. The table below has been chosen because it reflects the clinical experience of Professor Ashton in having helped over 300 people to withdraw from benzodiazepines by use of a Valium substitution method (see below).


Alcohol .5-2 hours 4 units (4 glasses of wine)
1. All these drugs are recommended for short-term use only (2-4 weeks maximum).
2. Half-life: time taken for blood concentration to fall to half its peak value after a single dose. Half-life of active metabolite shown in square brackets. This time may vary considerably between individuals.
3. These equivalents do not agree with those used by some authors. They are firmly based on clinical experience during switch-over to diazepam at start of withdrawal programs but may vary between individuals.
4. Market Aim: Although all benzodiazepines have similar actions, they are usually marketed as anxiolytics (a), hypnotics (h) or anticonvulsants (e).
5. In the UK clobazam (Frisium) and clonazepam (Rivotril) are licensed for use as anti-epileptics only.
6. These drugs are chemically different from benzodiazepines but have the same effects on the body and act by the same mechanisms.


Thus, 1mg of alprazolam (Xanax) or clonazepam (Klonopin) is the equivalent of 20mg of Valium; 1mg of lorazepam (Ativan) is the equivalent of 10mg of Valium.

These dose equivalencies are important for a number of reasons, the most significant of which is the issue of switching to a different benzodiazepine such as Valium prior to tapering (see below). These figures are taken from Professor Ashton's Manual (see below) and several other sources. See for example the Benzo Equivalence Table on this site.

You may find a doctor who will want to switch you from Xanax to Valium at a 1mg to 10mg equivalency. This is a recipe for a very diffi. cross-over. Whatever the precise therapeutic dose equivalencies, the above equivalencies should be observed in switching from one benzodiazepine to another for purposes of withdrawal (see below).

5. WHAT IS A "HALF-LIFE", AND HOW IS THE CONCEPT IMPORTANT TO BENZODIAZEPINE DEPENDENCE?

Half-life is a numerical expression of how long it takes for a drug to leave your body. Technically, the "half-life," expressed as a range, is the time it takes for half of the amount consumed to be eliminated from your body, and so on. There is some controversy as to how long benzodiazepines may actually remain in your body after you have discontinued them entirely. Benzodiazepines are fat soluble and can persist in fatty tissues. However, benzodiazepines no longer show up in blood screenings beyond 30 days after discontinuance. This either means they are totally eliminated by that time, or that they persist in amounts too small to have any long term effect.

The importance of half-life is that a longer half-life generally makes for an easier withdrawal because your blood levels remain relatively constant, as opposed to the up and down roller coaster that you experience with short half life benzodiazepines. Furthermore, longer half-life benzodiazepines require less dose micro-management. For example, Valium can be taken once every 12 hours, or in some cases, once every 24 hours. Xanax, however, must be taken once every 4-6 hours to maintain constant blood levels. This is a practical impossibility for some people.

The following is a list of benzodiazepines with their corresponding half-lives, expressed as a range in hours:



There is a misconception that longer half-life benzodiazepines prolong the withdrawal recovery process by remaining in your body tissues for longer. However, there is no evidence that longer half-life benzodiazepines represent any greater risk for Protracted Benzodiazepine Withdrawal Syndrome (see below) than shorter half-life benzodiazepines. This method of using a longer half-life equivalent is well understood in addiction medicine circles, and is employed with other classes of drugs as well. For example, people who are experiencing withdrawal symptoms from an antidepressant such as Paxil (Seroxat, paroxetine) are often given Prozac (fluoxetine) as a substitute for purposes of withdrawal, because Prozac has a longer half-life. Perhaps a more typical example is the use of the drug Methadone in heroin detoxification, which is employed in part because of its relatively long half-life.

6. WHAT DOES "TOLERANCE" MEAN?

Tolerance is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependency.

7. IF MY DOCTOR HAS PRESCRIBED A BENZODIAZEPINE AND INSTRUCTED ME TO TAKE IT FOR A MEDICAL AND/OR PSYCHOLOGICAL REASON, IS THERE ANY REASON I SHOULD DISREGARD MY DOCTOR'S ADVICE AND DISCONTINUE THE BENZODIAZEPINE?

Yes, there may be. Unfortunately, there are many well-intended physicians who simply do not understand the seriousness of long-term benzodiazepine use.

Regular benzodiazepine use almost always causes some degree of deterioration in cognitive functioning, which progresses with continued use.

Long term benzodiazepine use also causes lethargy and decreased energy levels that result in impairment in work productivity and disinclination towards exercise.

Furthermore, benzodiazepines, and all other classes of sedatives, frequently cause and/or worsen depression. This is why people are often given antidepressants after being given a benzodiazepine for anxiety. Antidepressants have their own complications and potential for dependency (see below).

Benzodiazepines can also cause what is sometimes referred to as a "emotional anaesthesia", or "emotional blunting," in which the user's ability to experience powerful emotions is impaired. This has been described as "the inability to feel pleasure or pain" in the medical literature (e.g. Ashton C H, Toxicity and Adverse Consequences of Benzodiazepine Use, 1995). Long-term benzodiazepine users often describe their experience as "sleepwalking through life".

Benzodiazepine use can also cause what are referred to as "paradoxical" symptoms in a minority of users. Paradoxical symptoms are contrary to the intended therapeutic purpose, including outbursts of rage, increased anxiety, and sleeplessness. Paradoxical symptoms can be caused by the drug's interaction with the psychological makeup of the user, or may be a biological reaction to use of the drug that people sometimes refer to as "toxicity". Paradoxical symptoms are sometimes mistaken for withdrawal, and vice versa. See: Benzodiazepines: Paradoxical Reactions & Long-Term Side-Effects. For further discussion on the long-term effects of benzodiazepines see: Benzodiazepines and their effects by Professor Ian Hindmarch.

The above effects occur to varying degrees, depending on the individual. Some individuals may not experience many of the effects at all. However, one effect is common to virtually all users: a physical dependency will eventually form. Benzodiazepine dependency is particularly serious as the withdrawal syndrome (see below) can be extremely diffi. and protracted. Furthermore, the development of tolerance often makes long term use non-feasible, and withdrawal becomes a necessary eventuality.

Benzodiazepines are often misprescribed for conditions to which they are not appropriate, such as depression. Furthermore, they are often prescribed for anxiety conditions for which the individual could be treated effectively with other therapeutic techniques.

There are, however, legitimate therapeutic benefits for benzodiazepines, particularly if they are used in the short term (no more than 2 weeks of continuous use), or for situational anxiety/panic (for example, one dose of Xanax per month as the need arises.) Furthermore, many users of benzodiazepines, including some who have used them regularly for more than a year, are able to discontinue them with little diffi.y.

Nothing in this FAQ is to be construed as advising any individual to ignore the advice of his or her physician. Decisions regarding the use or discontinuation of any benzodiazepine should be made in consultation with a physician. However, in this area you must also undertake considerable self-education in addition to listening carefully to your doctor's advice. Fortunately, there are many available resources to accomplish that (see below). Where a doctor does not appear to be up to date with current medical literature regarding benzodiazepine dependency and the withdrawal syndrome, seeking a second and third medical opinion can be a desirable option.

8. WHAT IS THE BENZODIAZEPINE WITHDRAWAL SYNDROME?

The Benzodiazepine Withdrawal Syndrome is believed to be caused by a dampening of the action of GABA as neuroadaptivity causes GABA to become dependent on stimulation from the benzodiazepine to initiate its primary action. In other words, when you have become dependent upon a benzodiazepine, your GABA is unable to perform its natural action without the presence of the benzodiazepine. This results in a wide variety of over-activity in different areas of your brain, causing a vast and diffuse array of symptoms. These symptoms are believed to be various manifestations of neurological over-excitation as the cells in your brain become especially sensitive to the action of excitatory neurotransmitters. The most extreme manifestation of this over-excitation is a seizure event.

The Benzodiazepine Withdrawal Syndrome is noted both for its relative severity and, in some cases, its lengthy duration, as compared to withdrawal from other classes of drugs.

Withdrawal either occurs through the development of tolerance without an attendant increase in dose, or through a decrease in dosage below your "tolerance point". Your tolerance point is the dose point below which the functioning of your receptors becomes impaired due to a deficiency in stimulation from the drug. Your tolerance point may be lower than your actual dosage, such that you can sometimes cut your dose by some amount without experiencing withdrawal symptoms.

Generally, a drug's withdrawal syndrome is the mirror of its primary effects. Thus, for benzodiazepines, you can expect sleeplessness (the mirror of its hypnotic effect), anxiety (the mirror of its anxiolytic effect), muscle tension/pain (the mirror of its muscle relaxant effect), and seizures in rare cases (the mirror of its anti-seizure effect). The only exception is that the Benzodiazepine Withdrawal Syndrome does not "mirror" the amnesic effect. On the contrary the Withdrawal Syndrome often results in increased impairment of memory and cognitive functioning. However, in all cases, after the withdrawal is complete and in total remission, cognitive functioning will gradually return to the level that it was at before you began using the drug.

For a more complete list of symptoms, see below.

9. WHAT ARE THE SYMPTOMS OF BENZODIAZEPINE WITHDRAWAL?

The following is a list of symptoms. As they have been reported by enough individuals they are statistically likely to be legitimate withdrawal symptoms. Keep in mind that there are a wide variety of other symptoms that have been reported that may be legitimate withdrawal symptoms as well, but have not been reported by enough individuals to be statistically significant. The determination of statistical significance is not based on hard data, but on the observations of this author in reading through thousands of posts from people in withdrawal, as well as several books and articles on the subject.

This list is broken down into psychological and physical symptoms. The double asterisk (**) indicates symptoms that occur to some degree or another, at one time or another, in virtually every person experiencing benzodiazepine withdrawal. Single asterisk (*) are symptoms that are common, and occur in most people. Others are symptoms that are common enough to be verifiable withdrawal symptoms, but probably occur in a minority of cases.

Psychological symptoms: anxiety** (including panic attacks), depression**, insomnia*, derealisation/depersonalisation* (feelings of unreality/detachment from self), obsessive negative thoughts*, (particularly of a violent and/or sexual nature) rapid mood changes* (especially including outbursts of anger or rage), phobias* (especially agoraphobia and fear of insanity), dysphoria* (loss of capacity to enjoy life; possibility a combination of depression, anxiety, and derealisation/depersonalisation), impairment of cognitive functioning*, suicidal thoughts*, nightmares, hallucinations, psychosis, pill cravings. Note that it is far more common to fear psychosis than it is to actually experience it.

Physical Symptoms: abnormal sensitivity to sensory stimuli* (such as loud noise or bright light), muscle tension/pain**, joint pain*, tinnitus*, headaches*, shaking/tremors*, blurred vision* (and other complications related to the eyes), itchy skin* (including formication, ie sensations of insects crawling on skin), gastrointestinal discomfort*, electric shock sensations*, paraesthesiae* (numbness and pins and needles, especially in extremities), fatigue*, weakness in the extremities* (particularly the legs), feelings of inner vibrations* (especially in the torso), sweating, fluctuations in body temperature, diffi.y in swallowing, loss of appetite, "flu like" symptoms, fasciculations (muscle twitching), metallic taste in mouth, nausea, extreme thirst (including dry mouth and increased frequency of urination), sexual dysfunction (or occasional increase in libido), heart palpitations, dizziness, vertigo, breathlessness.

Here, I have cited only the most commonly reported withdrawal symptoms. For more comprehensive lists of withdrawal symptoms see the Symptoms Index on this site.