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

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Certain individuals respond very well to yoga and meditation techniques. One particular patient who was confined to a wheelchair with a spastic paralysis and who was also blind, was able to come off all his benzodiazepines with the help of a meditation technique. His spasticity actually improved. However, not everyone is able to devote the mental and physical concentration required for these techniques. Physical exercise, within your own limitations, is good for everyone. Most of the people attending the clinic had been taking benzodiazepines prescribed by their doctors for many years, sometimes over 20 years. They wished to stop because they did not feel well. They realised that the drugs, though effective when first prescribed, might now be actually making them feel ill. They had many symptoms, both physical and mental. Some were depressed and/or anxious; some had "irritable bowel", cardiac or neurological complaints. Many had undergone hospital investigations with full gastrointestinal, cardiological and neurological screens (nearly always with negative results). A number had been told (wrongly) that they had multiple sclerosis. Several had lost their jobs through recurrent illnesses. 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.

Drug withdrawal reactions in general tend to consist of a mirror image of the drugs’ initial effects. In the case of benzodiazepines, sudden cessation after chronic use may result in dreamless sleep being replaced by insomnia and nightmares; muscle relaxation by increased tension and muscle spasms; tranquillity by anxiety and panic; anticonvulsant effects by epileptic seizures. These reactions are caused by the abrupt exposure of adaptations that have occurred in the nervous system in response to the chronic presence of the drug. Rapid removal of the drug opens the floodgates, resulting in rebound overactivity of all the systems which have been damped down by the benzodiazepine and are now no longer opposed. Nearly all the excitatory mechanisms in the nervous system go into overdrive and, until new adaptations to the drug-free state develop, the brain and peripheral nervous system are in a hyperexcitable state, and extremely vulnerable to stress. Acute withdrawal symptoms I hardly dare to mention smoking in view of present day attitudes to this unfortunate addiction, but for those who are smokers it is probably asking too much to attempt to stop smoking and withdraw benzodiazepines at the same time. Many people have found that giving up smoking is easier when they are off benzodiazepines, when the desire for nicotine may even wane somewhat. In general, excessive worrying over your undesirable habits (or your diet) can add to the stress of withdrawal. It is better to relax a bit and be gentle with yourself. COURSE OF WITHDRAWAL Memory impairment. Benzodiazepines have long been known to cause amnesia, an effect which is utilised when the drugs are used as premedication before major surgery or for minor surgical procedures. Loss of memory for unpleasant events is a welcome effect in these circumstances. For this purpose, fairly large single doses are employed and a short-acting benzodiazepine (e.g. midazolam) may be given intravenously. On the whole, different approaches suit different individuals and need to be personalised. If you believe in a certain approach, it will probably do you good. Sensory hypersensitivity Biochemical alterations caused by benzodiazepines (serotonin, norepinephrine [noradrenaline], stress hormones)

Discontinuing after short-term use

Considerable loss of weight (8-10lb or more) sometimes occurs in withdrawal. This may be due to a rebound effect on appetite, since benzodiazepines have been shown to increase appetite in animals. On the other hand, some people gain weight in withdrawal. In any case, weight changes are not severe enough to worry about and normal weight is soon regained after withdrawal. A few people have difficulty in swallowing food – the throat seems to tighten up especially if eating in company. This is usually a sign of anxiety and is well-known in anxiety states. Practising relaxation, eating alone, taking small well chewed mouthfuls with sips of liquid and not hurrying make things easier and the symptom settles as anxiety levels decline. Guided imaging (focus on pleasant, relaxing situations; relaxation tapes with music and calm words can also be used at home) Coping skills therapy/anxiety management (learning techniques) to avoid anxiety-provoking situations and to deal with anxiety (if it occurs) In the UK clobazam (Frisium) and clonazepam (Rivotril) are licensed for use as anti-epileptics only.

Sensory symptoms: tinnitus, tingling, numbness, deep or burning pain in limbs, feeling of inner trembling or vibration, strange skin sensations In my clinic, nerve conduction studies in patients with such symptoms revealed nothing abnormal – for example, there was no evidence of peripheral neuritis. However, the symptoms were sometimes enough to puzzle neurologists. Three patients with a combination of numbness, muscle spasms and double vision were diagnosed as having multiple sclerosis. This diagnosis, and all the symptoms, disappeared soon after the patients stopped their benzodiazepines. Symptoms of a chronic hyperactive nervous system persisting after withdrawal are listed in the Manual Chapter 3, Table 3. Ashton, H. Toxicity and adverse consequences of benzodiazepine use. Psychiatric Annals (1995) 25,158-165.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. Take much slower and deeper breaths, making sure that you get air deep down into the lungs instead of just at the top of the chest.” People with such worries can be reassured. All the evidence shows that a steady decline in symptoms almost invariably continues after withdrawal, though it can take a long time – even several years in some cases. Most people experience a definite improvement over time so that symptoms gradually decrease to levels nowhere near as intense as in the early days of withdrawal, and eventually almost entirely disappear. All the studies show steady, if slow, improvement in cognitive ability and physical symptoms. Although most studies have not extended beyond a year after withdrawal, the results suggest that improvement continues beyond this time. There is absolutely no evidence that benzodiaze

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. 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. The same principles apply to food. Humans are singularly well adapted through evolution to obtain the nutrients they need from a wide variety of diets and to eliminate unwanted products. A normal healthy diet which includes generous amounts of fruit and vegetables and a source of protein and fats (from meat or vegetables), and not too much pure sugar or “junk foods”, provides all the nutrients a person needs. There is no general need for dietary supplements or extra vitamins or minerals or for “detoxifying” measures. All these can be harmful in excess. Advice to cut out white flour, white sugar etc. may help certain individuals but I have also observed that overly restrictive diets can have adverse effects. Some people say they have felt much better after going on a particular diet – this makes one wonder what sort of diet they were eating before! T he benzodiazepine withdrawal symptom that raises most fear of going mad is hallucination. Terrifying hallucinations have occurred in people undergoing rapid or abrupt withdrawal from high doses, but the reader can be reassured that they are exceedingly rare with slow dosage tapering as outlined in Chapter II. If hallucinations occur, they are usually visual – patients have described hallucinations of a large bat sitting on the shoulder, or the appearance of horns sprouting from a human head – but auditory, olfactory and tactile hallucinations can also occur. Somewhat less frightening are hallucinations of small creatures, usually insects, which may be associated with the sensations of insects crawling on the skin (similar hallucinations occur in cocaine and amphetamine withdrawal). Sometimes hallucinations merge with illusions and misperceptions. For example, a coat hanging on the door may give the illusion of being a person. Floors apparently tilting and walls that seem to slope inwards are perceptual distortions.Impairment of memory caused by benzodiazepines prevents normal resolution of distressing life events which are exposed on withdrawal None of these symptoms is harmful, and they need not be a cause of worry once they are understood. The muscle pain and stiffness is actually little different from what is regarded as normal after an unaccustomed bout of exercise, and would be positively expected, even by a well-trained athlete, after running a marathon.

Readers may well ask: Why do we have specific benzodiazepine receptors in our brain? They have clearly not evolved over thousands and millions of years just to sit there and wait until Valium arrived! Most drugs that affect the brain act on receptors that are already there, and all of these drugs have subsequently been found to take the place of natural substances synthesised within the body. For example, the receptors for morphine react with natural endogenous endorphins and enkephalins, the physiological pain-killers; the receptors for cannabis are normally stimulated by natural substances called anandamides (named after the Sanskrit word ananda, which means "bliss"); nicotine in tobacco reacts with nicotine receptors for the natural neurotransmitter acetylcholine; all the psychotropic drugs like antidepressants and antipsychotics affect the receptor for natural neurotransmitters such as serotonin, noradrenaline and dopamine. The conclusion from such discoveries is that there must exist a natural benzodiazepine which normally modulates the activity of GABA at GABA/benzodiazepine receptors, like diazepam, and acts as an inborn, calming, sleep-inducing and anticonvulsant agent. 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.Apart from their therapeutic effects in depression and anxiety, some antidepressants have a sedative effect which patients who are particularly plagued with insomnia have found helpful. Low doses (10-50mg) of amitriptyline (Elavil) or doxepin (Sinequan) are remarkably effective in promoting sleep if taken at bed-time. These can be taken for short periods of a few weeks and stopped by reducing the dosage stepwise or taking the drug every other night. Withdrawal is not a problem when small doses are taken for short periods or intermittently. TABLE 2. ANTIDEPRESSANT WITHDRAWAL SYMPTOMS Chapter I described what benzodiazepines do when they are in the body and how tolerance and dependence develop. Chapter II discussed the need for slow withdrawal and gave practical examples of dosage tapering. This chapter is concerned with what happens as benzodiazepines leave the body in the course of withdrawal and afterwards. The focus is on withdrawal symptoms, and how to cope with them if they occur. These days when multi-ethnic populations, including many people of Asian extraction, exist world-wide, doctors and psychiatrists may need to be reminded that in Asian patients, benzodiazepine (and antidepressant or antipsychotic) prescriptions, if considered necessary, should be started at half the standard dose in case they are poor or slow metabolisers. Depression, emotional blunting. Long-term benzodiazepine users, like alcoholics and barbiturate-dependent patients, are often depressed, and the depression may first appear during prolonged benzodiazepine use. Benzodiazepines may both cause and aggravate depression, possibly by reducing the brain's output of neurotransmitters such as serotonin and norepinephrine (noradrenaline). However, anxiety and depression often co-exist and benzodiazepines are frequently prescribed for mixed anxiety and depression. Sometimes the drugs seem to precipitate suicidal tendencies in such patients. Of the first 50 of the patients attending my withdrawal clinic ( reported in 1987), ten had taken drug overdoses requiring hospital admission while on chronic benzodiazepine medication; only two of these had a history of depressive illness before they were prescribed benzodiazepines. The depression lifted in these patients after benzodiazepine withdrawal and none took further overdoses during the 10 months to 3.5 years follow-up period after withdrawal. In 1988 the Committee on Safety of Medicines in the UK recommended that "benzodiazepines should not be used alone to treat depression or anxiety associated with depression. Suicide may be precipitated in such patients".

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