Benzodiazepines: How They Work and How to Withdraw (aka The Ashton Manual)

Product Information

The advice and explanations given in the Supplement may seem inadequate. They no doubt illustrate how much more we still need to know about benzodiazepines. However, it is important to remember that by far the greatest majority of long-term benzodiazepine users do recover from withdrawal - given time. Even protracted symptoms tend to decrease gradually, sometimes over years. The individual needs to know that the actual drug withdrawal is only the first step towards recovery. It may be followed by a prolonged period of convalescence during which the damage caused to the person's body - and often to his whole life - needs to be repaired as far as possible. But the brain, like the rest of the body, has an enormous capacity for adapting and self-healing. That is how life survives and how ex-benzodiazepine 'addicts' can be optimistic about their future. Potency. A large number of benzodiazepines are available ( Table 1). There are major differences in potency between different benzodiazepines, so that equivalent doses vary as much as 20-fold. For example, 0.5 milligrams (mg) of alprazolam (Xanax) is approximately equivalent to 10mg of diazepam (Valium). Thus a person on 6mg of alprazolam daily, a dose not uncommonly prescribed in the US, is taking the equivalent of about 120mg of diazepam, a very high dose. These differences in strength have not always been fully appreciated by doctors, and some would not agree with the equivalents given here. Nevertheless, people on potent benzodiazepines such as alprazolam, lorazepam (Ativan) or clonazepam (Klonopin) tend to be using relatively large doses. This difference in potency is important when switching from one benzodiazepine to another, for example changing to diazepam during the withdrawal, as described in the next chapter. 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. Fig. 1. Diagram of mechanism of action of the natural neurotransmitter GABA (gamma aminobutyric acid) and benzodiazepine on nerve cells (neurons) in the brain Such experiences probably represent a normal defensive reaction evolved as a protection against intolerable suffering. They may involve a primitive brain mechanism similar to the “freezing” of some animals when presented with an inescapable danger. Like other benzodiazepine withdrawal symptoms, these feelings resolve in time and should not be interpreted as abnormal or crazy. Hallucinations, illusions, perceptual distortions

In the UK clobazam (Frisium) and clonazepam (Rivotril) are licensed for use as anti-epileptics only.Although it is well known that benzodiazepines impair memory and some cognitive functions, particularly the ability to sustain attention, some long-term users complain of continued loss of intellectual abilities persisting after withdrawal. There have been several studies on this question which indicate that improvement may be very slow. The longest studies in therapeutic dose long-term users extend for only 10 months after withdrawal. Cognitive impairment, though slowly improving, persisted for at least this time and was not related to anxiety levels (Tata et al. Psychological Medicine 1994, 24, 203-213). Some Swedish studies have found that intellectual impairment, although improved, was still present 4-6 years after cessation of benzodiazepine use, but it was not clear whether high dosage and/or alcohol use were added factors. Do benzodiazepines cause structural brain damage? Depression may be caused or aggravated by chronic benzodiazepine use, but is also a feature of the withdrawal syndrome. Depressive symptoms may appear for the first time after withdrawal, sometimes after a delay of a few weeks, and it can be severe and protracted for some months. It is not clear whether people who have had depression before, or have a family history of depression, are more prone to this complication, and its causes are not understood. As discussed in Chapters I and II, benzodiazepines disrupt the function of many neurotransmitters and hormones and depression could be the result, for example, of low serotonin activity combined with the stress of withdrawal. If severe enough to require definitive treatment, the depression in withdrawal responds to antidepressant drugs and/or cognitive therapy and usually diminishes gradually over 6-12 months. Insomnia

Most digestive symptoms get better after withdrawal but in a few people they persist and become a protracted symptom, raising fears of food allergy or candida infection. These questions are discussed further in the section on protracted symptoms. Immune system Similarly with alcohol: a glass or two of wine is perfectly permissible (and even said by some to be advisable for health). Although it is important not to substitute increasing doses of alcohol for decreasing doses of benzodiazepines, there is no need to deny oneself small pleasures. Moderation is the key: there is no call to be puritanical. Feelings of depersonalisation and of unreality are associated with benzodiazepine withdrawal, although they also occur in anxiety states. They occur most often during over-rapid withdrawal from potent benzodiazepines and are, anecdotally, particularly marked on withdrawal from clonazepam (Klonopin). In these states, the person seems detached from his body and seems almost to be observing it from the outside. Similar experiences are described in near-death states when the individual feels that he is hovering above his body, detached from the events occurring below. They are also described by people involved in extreme emergencies and in individuals subjected to torture. They are clearly not specific to benzodiazepines. Ashton, H. Benzodiazepine withdrawal: outcome in 50 patients. British Journal of Addiction (1987) 82,665-671. There is still much to discover about endozepines. Some inhibit diazepam binding and may therefore be anxiogenic while others appear to act like diazepam and enhance GABA activity (as explained in the Manual, Chapter 1). It seems likely that the balance between different endozepines acting at the GABA-A receptor may determine an individual's susceptibility to anxiety and response to benzodiazepine drugs by acting as 'fine-tuners' of GABA-A function.

The most prominent effect of benzodiazepines is an anti-anxiety effect – that is why they were developed as tranquillisers. As a consequence, nearly all the acute symptoms of withdrawal are those of anxiety. They have been described in anxiety states in people who have never touched a benzodiazepine and were recognised as psychological and physical symptoms of anxiety long before benzodiazepines were discovered. However, certain symptom clusters are particularly characteristic of benzodiazepine withdrawal. These include hypersensitivity to sensory stimuli (sound, light, touch, taste and smell) and perceptual distortions (for example sensation of the floor undulating, feeling of motion, impressions of walls or floors tilting, sensation of walking on cotton wool). There also appears to be a higher incidence than usually seen in anxiety states of depersonalisation, feelings of unreality, and tingling and numbness. Visual hallucinations, distortion of the body image (“my head feels like a football/balloon”), feelings of insects crawling on the skin, muscle twitching and weight loss are not uncommon in benzodiazepine withdrawal but unusual in anxiety states. A normal diet includes a normal amount of fluid consumption. Requirements for water and salt vary with body size, environmental temperature, amount of exercise, etc. so cannot be stated categorically. However, there is no need to drink extra amounts of fluid during withdrawal with the idea of “flushing out impurities/toxins”. The body is very good at doing this, even at minimal fluid consumption, and surplus water is simply excreted.

They have continued to take benzodiazepines although the original indication for prescription has disappeared. Recreational use of diazepam, alprazolam, lorazepam, temazepam, triazolam, flunitrazepam and others has been reported in various countries. Usually the drugs are taken orally, often in doses much greater than those used therapeutically (e.g.100mg diazepam or equivalent daily) but some users inject benzodiazepines intravenously. These high dose users develop a high degree of tolerance to benzodiazepines and, although they may use the drugs intermittently, some become dependent. Detoxification of these patients may present difficulties since withdrawal reactions can be severe and include convulsions.

Some people have no problems at all with their digestive systems during or after withdrawal, and may even notice that they are enjoying their food more. Others, perhaps more prone constitutionally, may complain of a range of symptoms associated with “irritable bowel syndrome” (IBS). These can include nausea, vomiting, diarrhoea, constipation, abdominal pain, flatulence, gaseous distension and heartburn. Quite a few have found these symptoms so uncomfortable that they have undergone hospital gastrointestinal investigations, but usually no abnormality is found. The symptoms may be partly due to overactivity in the autonomic nervous system, which controls the motility and secretions of the gut and is very reactive to stress, including the stress of benzodiazepine withdrawal. In addition, there are benzodiazepine receptors in the gut. It is not clear what the functions of these receptors are or how they are affected by benzodiazepines or benzodiazepine withdrawal, but alterations in these receptors may play some part in increasing gut irritability. Coping skills therapy/anxiety management (learning techniques) to avoid anxiety-provoking situations and to deal with anxiety (if it occurs) GABA reacts with receptors on neuron 2; the reaction allows chloride ions (Cl -) to enter the neuron Do not move on until you feel the tension flowing out of your hands. With each deep breath you should feel your tension flowing away and, as it does, your symptoms will lessen or disappear.”