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

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For a discussion of half-lives and equivalencies see also the Benzo FAQ document. Benzodiazepines 1 In the UK clobazam (Frisium) and clonazepam (Rivotril) are licensed for use as anti-epileptics only.

It is not unusual to experience recurrence of apparent benzodiazepine withdrawal symptoms years after a successful withdrawal and a return to normal health. The particular pattern of symptoms is unique to the individual, depending on his physical and psychological makeup, and no doubt on the innate density of his/her benzodiazepine receptors and the balance of his endozepines (see above). The experience of benzodiazepine withdrawal is deeply etched into the mind and memory of those who have been through it, and is actually physically present in the strength and connections of their neural synapses, as all memories are. These recurrent symptoms are all signs of GABA underactivity with its accompanying increased output of excitatory neurotransmitters, resulting in a hyperactive, hypersensitive central nervous system. The mechanism is exactly the same as that of benzodiazepine withdrawal, which is why the symptoms are the same. If sleep is really a problem, a small dose of a tricyclic antidepressant with sedative effects (see antidepressants, above) is a possible option. Alternatively, an antihistamine with sedative effects (e.g. diphenylhydramine [Benadryl], promethazine [Phenergan]) may be used temporarily. Neither antidepressants nor antihistamines act by the same mechanisms as benzodiazepines. Why do apparent recurrences of benzodiazepine withdrawal symptoms occur, (often a long time after) successful withdrawal?It cannot be too strongly stressed that withdrawal symptoms can be minimised and largely avoided by slow tapering, tailored to the individual’s needs as outlined in Chapter II. However, some long-term benzodiazepine users begin to experience “withdrawal” symptoms even though they continue taking the drug. This is due to the development of drug tolerance ( Chapter I) which sometimes leads doctors to increase the dosage or add another benzodiazepine. Analysis of the first 50 patients who attended my benzodiazepine withdrawal clinic showed that all of them had symptoms on first presentation while still on benzodiazepines (12 of them were taking two prescribed benzodiazepines at once). Their symptoms included the full range of psychological and physical symptoms usually described as benzodiazepine withdrawal symptoms. The process of slow benzodiazepine tapering in these patients caused only slight exacerbation of these symptoms, which then declined after withdrawal. 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. There are many non-pharmacological techniques for helping people with anxiety. Some of these are listed below, but it is beyond the scope of this booklet to give details of each technique or to mention all of them. None of them are essential for everybody coming off tranquillisers, but can be helpful for those having difficulty. (1) PsychologicalTechniques There has been little clinical progress in the benzodiazepine world since 2002 when the last edition of "Benzodiazepines: How they work and how to withdraw" appeared on www.benzo.org.uk. Benzodiazepines are still over-prescribed globally, often in excessive doses and frequently for too long. Prescriptions for benzodiazepines and the similar 'Z-drugs' are actually increasing in many countries. There is a tendency to prescribe the more potent agents such as clonazepam (Klonopin) and, in the U.S. particularly, alprazolam (Xanax) and zolpidem (Ambien), while lorazepam (Ativan) is still the most commonly prescribed drug for anxiety. The availability of benzodiazepines on the internet has increased their use as 'self-medication' in the general public who are often unaware of their adverse effects and dependence potential. This availability has also added to benzodiazepine use in multidrug abusers. Of the complementary medicine techniques, all can help with relaxation during the procedure but the effects tend to be short-lived. For example, patients in my clinic who underwent a course of 12 acupuncture sessions by an acupuncturist trained in both Chinese and Western acupuncture enjoyed and felt relaxed by the sessions but they did not do any better in the long run than others who did not have acupuncture.

The choice of, and response to, each of these measures depends very much on the individual. The various psychological techniques have been formally tested and give the best long-term results. However, the outcome depends largely on the skill of the therapist, including his/her knowledge of benzodiazepines, and the rapport between therapist and client. It is not clear whether there really is an increased incidence of infections in people undergoing benzodiazepine withdrawal, because there have been no comparisons with otherwise similar populations who have not been exposed to benzodiazepines. However, many factors affect the immune system. One of these is stress, with increased output of the stress hormone, cortisol, which inhibits immune responses. Another factor is depression, also related to stress and associated with increased cortisol secretion. Increased cortisol levels can reduce resistance to infection and also cause flare-ups of incipient infection. Benzodiazepine withdrawal can clearly be stressful but, strangely, in patients that I have tested, blood cortisol concentrations have been low. So this subject remains a mystery and probably merits further research. The message for people undergoing benzodiazepine withdrawal is to try to lead a healthy lifestyle, which includes a balanced diet, plenty of exercise and rest, and avoidance of extra stress where possible. Slow dosage tapering ( Chapter II) is the best way to reduce the stress of withdrawal. Endocrine problems Adverse effects in the elderly. Older people are more sensitive than younger people to the central nervous system depressant effects of benzodiazepines. Benzodiazepines can cause confusion, night wandering, amnesia, ataxia (loss of balance), hangover effects and "pseudodementia" (sometimes wrongly attributed to Alzheimer’s disease) in the elderly and should be avoided wherever possible. Increased sensitivity to benzodiazepines in older people is partly because they metabolise drugs less efficiently than younger people, so that drug effects last longer and drug accumulation readily occurs with regular use. However, even at the same blood concentration, the depressant effects of benzodiazepines are greater in the elderly, possibly because they have fewer brain cells and less reserve brain capacity than younger people. Some readers may decide to go directly to the chapter on benzodiazepine withdrawal ( Chapter II). However, those who wish to understand withdrawal symptoms and techniques (and therefore to cope better with the withdrawal process) are advised to become acquainted first with what benzodiazepines do in the body, how they work, how the body adjusts to chronic use, and why withdrawal symptoms occur. These issues are discussed in this chapter.They become anxious if the next prescription is not readily available; they may carry their tablets around with them and may take an extra dose before an anticipated stressful event or a night in a strange bed. One reassuring finding from many clinical studies is that eventual success in withdrawal is not affected by duration of use, dosage or type of benzodiazepine, rate of withdrawal, severity of symptoms, psychiatric diagnosis, or previous attempts at withdrawal. Thus from almost any starting point, the motivated long-term user can proceed in good heart. PROTRACTED WITHDRAWAL SYMPTOMS