These actions, exerted by different benzodiazepines in slightly varying degrees, confer on the drugs some useful medicinal properties. Few drugs can compete with them in efficacy, rapid onset of action and low acute toxicity. In short-term use, benzodiazepines can be valuable, sometimes even life-saving, across a wide range of clinical conditions as shown in Table 2. Nearly all the disadvantages of benzodiazepines result from long-term use (regular use for more than a few weeks). The UK Committee on Safety of Medicines in 1988 recommended that benzodiazepines should in general be reserved for short-term use (2-4 weeks only). A fascinating symptom in patients undergoing benzodiazepine withdrawal is that they often mention the occurrence of what seem to be intrusive memories. Their minds will suddenly conjure up a vivid memory of someone they have not thought about or seen for years. Sometimes the other person’s face will appear when looking in the mirror. The memory seems uncalled for and may recur, intruding on other thoughts. The interesting thing about these memories is that they often start to occur at the same time that vivid dreams appear; these may be delayed until one or more weeks after the dosage tapering has started. Since recent sleep research indicates that certain stages of sleep (REMS and SWS) are important for memory functions, it is likely that the dreams and the memories are connected. In both cases the phenomena may herald the beginning of a return in normal memory functions and, although sometimes disturbing, can be welcomed as a sign of a step towards recovery. Regular moderate exercise is recommended during withdrawal as it maintains general fitness, builds up stamina, increases the circulation to brain, muscle and skin and improves mood, but there is no point in slavishly doing exercises that you hate. The aim is to lead a healthy lifestyle which by definition includes some exercise in a form that is enjoyable for you. Smoking

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 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. They may have anxiety symptoms, panics, agoraphobia, insomnia, depression and increasing physical symptoms despite continuing to take benzodiazepines. A dilemma faced by some people in the process of benzodiazepine withdrawal, or after withdrawal, is what to do if they have intolerable symptoms which do not lessen after many weeks. If they are still taking benzodiazepines, should they increase the dose? If they have already withdrawn, should they reinstate benzodiazepines and start the withdrawal process again? This is a difficult situation which, like all benzodiazepine problems, depends to some degree on the circumstances and the individual, and there are no hard and fast rules. The advice given to prescribed benzodiazepine users (and their doctors) in the 'Ashton Manual' remains relevant today and requires little updating. This supplement adds further information in response to questions that have frequently been asked by benzodiazepine users during and after withdrawal. Such questions are difficult to answer because, like most benzodiazepine problems, they depend on many individual factors. Such factors include personality and genetic make-up, reasons for benzodiazepine prescription, dose, duration and type of benzodiazepine use, present symptoms, environmental stresses and others. Individuals seeking answers from the general information provided in this supplement need to work out which factors apply to them personally.

Discontinuing after short-term use

Pharmacologically, neither reinstating nor updosing is really rational. If withdrawal symptoms are still present, it means that the GABA/benzodiazepine receptors have not fully recovered (see above). Further benzodiazepines cause further down-regulation, strengthen the dependence, prolong withdrawal, delay recovery and may lead to protracted symptoms. In general, the longer the person remains on benzodiazepines the more difficult it is to withdraw. On the whole, anyone who remained benzodiazepine-free, or has remained on the same dose, for a number of weeks or months would be ill-advised to start again or to increase dosage. It would be better to devote the brain to solving individual symptoms and to finding sources of advice and support. Advice about how to deal with individual symptoms is given in the Manual (Chapter 3). 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. 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. Sensory symptoms: tinnitus, tingling, numbness, deep or burning pain in limbs, feeling of inner trembling or vibration, strange skin sensations

Severe depression may result from biochemical changes in the brain induced by benzodiazepines. Benzodiazepines are known to decrease the activity of serotonin and norepinephrine (noradrenaline), neurotransmitters believed to be closely involved in depression. Antidepressant drugs including the selective serotonin reuptake inhibitors (SSRIs such as Prozac) are thought to act by increasing the activity of such neurotransmitters.A number of people are expressing fears that some benzodiazepine withdrawal symptoms last for ever, and that they can never completely recover. Particular concerns have been raised about impairment of cognitive functions (such as memory and reasoning) and other lingering problems such as muscle pains and gastrointestinal disturbances. Fig. 1. Diagram of mechanism of action of the natural neurotransmitter GABA (gamma aminobutyric acid) and benzodiazepine on nerve cells (neurons) in the brain Flumazenil is thought to act by “resetting” GABA/benzodiazepine receptors (See Chapter I) so that they are more receptive to the inhibitory actions of GABA. The results suggest that some protracted symptoms are due to the failure of the receptors to revert to their normal state after they have become unresponsive to GABA, due to the development of tolerance (See Chapter I). The response to flumazenil also shows that benzodiazepines can cause longer-lasting pharmacological effects than previously believed. In the UK clobazam (Frisium) and clonazepam (Rivotril) are licensed for use as anti-epileptics only.