CHAPTER TWO (PART 1) CONTENTS

Background

Why should you come off benzodiazepines?

Before starting benzodiazepine withdrawal

• Consult your doctor and pharmacist
• Make sure you have adequate psychological support
• Get into the right frame of mind

• Be confident
• Be patient
• Choose your own way

The withdrawal

• Dosage tapering
• Switching to a long-acting benzodiazepine
• Designing and following the withdrawal schedule
• Withdrawal in older people
• Withdrawal of antidepressants

Further reading

BACKGROUND

At the start of my Benzodiazepine Withdrawal Clinic in 1982, no-one had much experience in benzodiazepine withdrawal. Yet, as explained in Chapter I, there was strong pressure from the patients themselves for help and advice on how to withdraw. So, together, we felt our way. At first the withdrawal was a process of mutual trial (and sometimes error), but through this experience some general principles of withdrawal - what works best for most people - emerged. These general principles, derived from the 300 who attended the clinic up till 1994, have been confirmed over succeeding years by hundreds more benzodiazepine users with whom I have been involved through tranquilliser support groups in the UK and abroad and by personal contacts with individuals in many countries.

It soon became clear that each person's experience of withdrawal is unique. Although there are many features in common, every individual has his/her own personal pattern of withdrawal symptoms. These differ in type, quality, severity, time-course, duration, and many other features. Such variety is not surprising since the course of withdrawal depends on many factors: the dose, type, potency, duration of action and length of use of a particular benzodiazepine, the reason it was prescribed, the personality and individual vulnerability of the patient, his or her lifestyle, personal stresses and past experiences, the rate of withdrawal, and the degree of support available during and after withdrawal, to name but a few. For this reason the advice about withdrawal which follows is only a general guide; each individual must seek out the details of his own pathway. But the guide is gleaned from the successful withdrawal experiences of a large number of men and women aged 18-80 with different home backgrounds, occupations, drug histories and rates of withdrawal. The success rate has been high (over 90%), and those who have withdrawn, even after taking benzodiazepines for over 20 years, have felt better both physically and mentally.

So, for those starting out, many previous users will testify that almost anyone who really wants to can withdraw from benzodiazepines. But don't be surprised if your symptoms (or lack of them) are different from those of anyone else embarking on the same venture.

WHY SHOULD YOU COME OFF BENZODIAZEPINES?

As described in Chapter I, long-term use of benzodiazepines can give rise to many unwanted effects, including poor memory and cognition, emotional blunting, depression, increasing anxiety, physical symptoms and dependence. All benzodiazepines can produce these effects whether taken as sleeping pills or anti-anxiety drugs. The social and economic consequences of chronic benzodiazepine use are summarised in Table 3 (Chapter I).

Furthermore, the evidence suggests that benzodiazepines are no longer effective after a few weeks or months of regular use. They lose much of their efficacy because of the development of tolerance. When tolerance develops, "withdrawal" symptoms can appear even though the user continues to take the drug. Thus the symptoms suffered by many long-term users are a mixture of adverse effects of the drugs and "withdrawal" effects due to tolerance. The Committee on Safety of Medicines and the Royal College of Psychiatrists in the UK concluded in various statements (1988 and 1992) that benzodiazepines are unsuitable for long-term use and that they should in general be prescribed for periods of 2-4 weeks only.

In addition, clinical experience shows that most long-term benzodiazepine users actually feel better after coming off the drugs. Many users have remarked that it was not until they came off their drugs that they realised they had been operating below par for all the years they had been taking them. It was as though a net curtain or veil had been lifted from their eyes: slowly, sometimes suddenly, colours became brighter, grass greener, mind clearer, fears vanished, mood lifted, and physical vigour returned.

Thus there are good reasons for long-term users to stop their benzodiazepines if they feel unhappy about the medication. Many people are frightened of withdrawal, but reports of having to "go through hell" can be greatly exaggerated. With a sufficiently gradual and individualised tapering schedule, as outlined below, withdrawal can be quite tolerable, even easy, especially when the user understands the cause and nature of any symptoms that do arise and is therefore not afraid. Many "withdrawal symptoms" are simply due to fear of withdrawal (or even fear of that fear). People who have had bad experiences have usually been withdrawn too quickly (often by doctors!) and without any explanation of the symptoms. At the other extreme, some people can stop their benzodiazepines with no symptoms at all: according to some authorities, this figure may be as high as 50% even after a year of chronic usage. Even if this figure is correct (which is arguable) it is unwise to stop benzodiazepines suddenly.

The advantages of discontinuing benzodiazepines do not necessarily mean that every long-term user should withdraw. Nobody should be forced or persuaded to withdraw against his or her will. In fact, people who are unwillingly pushed into withdrawal often do badly. On the other hand, the chances of success are very high for those sufficiently motivated. As mentioned before, almost anyone who really wants to come off can come off benzodiazepines. The option is up to you.

(1) Consult your doctor and pharmacist

Your doctor may have views on whether it is appropriate for you to stop your benzodiazepines. In a small number of cases withdrawal may be inadvisable. Some doctors, particularly in the US, believe that long-term benzodiazepines are indicated for some anxiety, panic and phobic disorders and some psychiatric conditions. However, medical opinions differ and, even if complete withdrawal is not advised, it may be beneficial to reduce the dosage or to take intermittent courses with benzodiazepine-free intervals.

Your doctor's agreement and co-operation is necessary since he/she will be prescribing the medication. Many doctors are uncertain how to manage benzodiazepine withdrawal and hesitate to undertake it. But you can reassure your doctor that you intend to be in charge of your own program and will proceed at whatever pace you find comfortable, although you may value his advice from time to time. It is important for you to be in control of your own schedule. Do not let your doctor impose a deadline. Leave yourself free to "proceed as the way openeth", as the Quakers say.

It is a good idea to make out a dosage reduction schedule for the initial stages (see below) and to give your doctor a copy. You may need to mention the importance of flexibility, so that the rate of dosage tapering can be amended at any time. There may even be circumstances when you need to stop for a while at a certain stage. A continuation schedule can follow later depending upon how you get on, and the doctor can continue prescribing in accordance with the new schedule. (All this is explained later in this chapter).

Finally, your doctor may appreciate receiving some literature on benzodiazepine withdrawal, for example the articles mentioned under Further Reading at the end of Chapters I & III and of this chapter.

(2) Make sure you have adequate psychological support

Support could come from your spouse, partner, family or close friend. An understanding doctor may also be the one to offer support as well as advice. Ideally, your mentor should be someone who understands about benzodiazepine withdrawal or is prepared to read about it and learn. It need not be someone who has gone through withdrawal - sometimes ex-users who have had a bad experience can frighten others by dwelling on their own symptoms. Often the help of a clinical psychologist, trained counsellor, or other therapist is valuable, especially for teaching relaxation techniques, deep breathing, how to deal with a panic attack etc. Some people find alternative techniques such as aromatherapy, acupuncture or yoga helpful, but these probably act only as an aid to relaxation. In my experience, hypnotherapy has not been helpful in long-term benzodiazepine users. Relaxation techniques are described in Chapter III.

Rather than (or in addition to) expensive therapists, you need someone reliable, who will support you frequently and regularly, long-term, both during withdrawal and for some months afterwards. Voluntary tranquilliser support groups (self-help groups) can be extremely helpful. They are usually run by people who have been through withdrawal and therefore understand the time and patience required, and can provide information about benzodiazepines. It can be encouraging to find that you are not alone, that there are plenty of others with similar problems to yours. However, do not be misled into fearing that you will get all the symptoms described by the others. Everyone is different and some people, with the right schedule and the right support, get no untoward symptoms at all. Many people in fact have managed to come off on their own without any outside help.

(3) Get into the right frame of mind

• Be confident - you can do it. If in doubt, try a very small reduction in dosage for a few days (for example, try reducing your daily dosage by about one tenth or one eighth; you may be able to achieve this by halving or quartering one of your tablets). You will probably find that you notice no difference. If still in doubt, aim at first for dosage reduction rather than complete withdrawal. You will probably wish to continue once you have started.

• Be patient. There is no need to hurry withdrawal. Your body (and brain) may need time to readjust after years of being on benzodiazepines. Many people have taken a year or more to complete the withdrawal. So don't rush, and, above all, do not try to stop suddenly.

• Choose your own way - don't expect a "quick fix". It may be possible to enter a hospital or special centre for "detoxification". Such an approach usually involves a fairly rapid withdrawal, is medically "safe" and may provide psychological support. Such centres may be suitable for a small minority of people with difficult psychological problems. However, they often remove the control of withdrawal from the patient and setbacks on returning home are common, largely because there has been no time to build up alternative living skills. Slow withdrawal in your own environment allows time for physical and psychological adjustments, permits you to continue with your normal life, to tailor your withdrawal to your own lifestyle, and to build up alternative strategies for living without benzodiazepines.

(1) Dosage tapering

There is absolutely no doubt that anyone withdrawing from long-term benzodiazepines must reduce the dosage slowly. Abrupt or over-rapid withdrawal, especially from high dosage, can give rise to severe symptoms (convulsions, psychotic reactions, acute anxiety states) and may increase the risk of protracted withdrawal symptoms (see Chapter III). Slow withdrawal means tapering dosage gradually, usually over a period of some months. The aim is to obtain a smooth, steady and slow decline in blood and tissue concentrations of benzodiazepines so that the natural systems in the brain can recover their normal state. As explained in Chapter I, long-term benzodiazepines take over many of the functions of the body's natural tranquilliser system, mediated by the neurotransmitter GABA. As a result, GABA receptors in the brain reduce in numbers and GABA function decreases. Sudden withdrawal from benzodiazepines leaves the brain in a state of GABA-underactivity, resulting in hyperexcitability of the nervous system. This hyperexcitability is the root cause of most of the withdrawal symptoms discussed in the next chapter. However, a sufficiently slow, and smooth, departure of benzodiazepines from the body permits the natural systems to regain control of the functions which have been damped down by their presence. There is scientific evidence that reinstatement of brain function takes a long time. Recovery after long-term benzodiazepine use is not unlike the gradual recuperation of the body after a major surgical operation. Healing, of body or mind, is a slow process.

The precise rate of withdrawal is an individual matter. It depends on many factors including the dose and type of benzodiazepine used, duration of use, personality, lifestyle, previous experience, specific vulnerabilities, and the (perhaps genetically determined) speed of your recovery systems. Usually the best judge is you, yourself; you must be in control and must proceed at the pace that is comfortable for you. You may need to resist attempts from outsiders (clinics, doctors) to persuade you into a rapid withdrawal. The classic six weeks withdrawal period adopted by many clinics and doctors is much too fast for many long-term users. Actually, the rate of withdrawal, as long as it is slow enough, is not critical. Whether it takes 6 months, 12 months or 18 months is of little significance if you have taken benzodiazepines for a matter of years.

It is sometimes claimed that very slow withdrawal from benzodiazepines "merely prolongs the agony" and it is better to get it over with as quickly as possible. However, the experience of most patients is that slow withdrawal is greatly preferable, especially when the subject dictates the pace. Indeed, many patients find that there is little or no "agony" involved. Nevertheless there is no magic rate of withdrawal and each person must find the pace that suits him best. People who have been on low doses of benzodiazepine for a relatively short time (less than a year) can usually withdraw fairly rapidly. Those who have been on high doses of potent benzodiazepines such as Xanax and Klonopin are likely to need more time.

Examples of slow withdrawal schedules are given at the end of this chapter. As a very rough guide, a person taking 40mg diazepam a day (or its equivalent) might be able to reduce the daily dosage by 2mg every 1-2 weeks until a dose of 20mg diazepam a day is reached. This would take 10-20 weeks. From 20mg diazepam a day, reductions of 1 mg in daily dosage every week or two might be preferable. This would take a further 20-40 weeks, so the total withdrawal might last 30-60 weeks. Yet some people might prefer to reduce faster and some might go even slower. (See next section for further details).

However, it is important in withdrawal always to go forwards. If you reach a difficult point, you can stop there for a few weeks if necessary, but you should try to avoid going backwards and increasing your dosage again. Some doctors advocate the use of "escape pills" (an extra dose of benzodiazepines) in particularly stressful situations. This is probably not a good idea as it interrupts the smooth decline in benzodiazepine concentrations and also disrupts the process of learning to cope without drugs which is an essential part of the adaptation to withdrawal. If the withdrawal is slow enough, "escape pills" should not be necessary.

(2) Switching to a long-acting benzodiazepine

With relatively short-acting benzodiazepines such as alprazolam (Xanax) and lorazepam (Ativan) (Table 1, Chapter I), it is not possible to achieve a smooth decline in blood and tissue concentrations. These drugs are eliminated fairly rapidly with the result that concentrations fluctuate with peaks and troughs between each dose. It is necessary to take the tablets several times a day and many people experience a "mini-withdrawal", sometimes a craving, between each dose.

For people withdrawing from these potent, short-acting drugs it is advisable to switch to a long-acting, slowly metabolised benzodiazepine such as diazepam. Diazepam (Valium) is one of the most slowly eliminated benzodiazepines. It has a half-life of up to 200 hours, which means that the blood level for each dose falls by only half in about 8.3 days. The only other benzodiazepines with similar half-lives are chlordiazepoxide (Librium), flunitrazepam (Rohypnol) and flurazepam (Dalmane), all of which are converted to a diazepam metabolite in the body. The slow elimination of diazepam allows a smooth, gradual fall in blood level, allowing the body to adjust slowly to a decreasing concentration of the benzodiazepines. The switch-over process needs to be carried out gradually, usually in stepwise fashion, substituting one dose at a time. There are several factors to consider. One is the difference in potency between different benzodiazepines. Many people have suffered because they have been switched suddenly to a different, less potent drug in inadequate dosage because the doctor has not adequately considered this factor. Equivalent potencies of benzodiazepines are shown in Table 1 (Chapter I), but these are only approximate and differ between individuals.

A second factor to bear in mind is that the various benzodiazepines, though broadly similar, have slightly different profiles of action. For example, lorazepam (Ativan) seems to have less hypnotic activity than diazepam (probably because it is shorter acting). Thus if someone on, say, 2mg Ativan three times a day is directly switched to 60mg diazepam (the equivalent dose for anxiety) he is liable to become extremely sleepy, but if he is switched suddenly onto a much smaller dose of diazepam, he will probably get withdrawal symptoms. Making the changeover one dose (or part of dose) at a time avoids this difficulty and also helps to find the equivalent dosage for that individual. It is also helpful to make the first substitution in the night-time dose, and the substitution may not always need to be complete. For example, if the evening dose was 2mg Ativan, this could in some cases be changed to 1 mg Ativan plus 8mg diazepam. A full substitution for the dropped 1 mg of Ativan would have been 10mg diazepam. However, the patient may actually sleep well on this combination and he will have already made a dosage reduction - a first step in withdrawal. (Examples of step-wise substitutions are given in the schedules at the end of this chapter.)

A third important practical factor is the available dosage formulations of the various benzodiazepines. In withdrawal you need a long-acting drug which can be reduced in very small steps. Diazepam (Valium) is the only benzodiazepine that is ideal for this purpose since it comes in 2mg tablets, which are scored down the middle and easily halved into 1 mg doses. By contrast, the smallest available tablet of lorazepam (Ativan) is 0.5mg (equivalent to 5mg diazepam) [in the UK the lowest available dosage form for lorazepam is 1mg]; the smallest tablet of alprazolam (Xanax) is 0.25mg (also equivalent to 5mg diazepam). Even by halving these tablets the smallest reduction one could easily make is the equivalent of 2.5mg diazepam. (Some patients become very adept at shaving small portions off their tablets). Because of limited dose formulations, it may be necessary to switch to diazepam even if you are on a fairly long-acting benzodiazepine of relatively low potency (e.g. flurazepam [Dalmane]). Liquid preparations of some benzodiazepines are available and if desired slow reduction from these can be accomplished by decreasing the volume of each dose, using a graduated syringe.

Some doctors in the US switch patients onto clonazepam (Klonopin, [Rivotril in Canada]), believing that it will be easier to withdraw from than say alprazolam (Xanax) or lorazepam (Ativan) because it is more slowly eliminated. However, Klonopin is far from ideal for this purpose. It is an extremely potent drug, is eliminated much faster than diazepam (See Table 1, Chapter I), and the smallest available tablet in the US is 0.5mg (equivalent to 10mg diazepam) and 0.25mg in Canada (equivalent to 5mg Valium). It is difficult with this drug to achieve a smooth, slow fall in blood concentration, and there is some evidence that withdrawal is particularly difficult from high potency benzodiazepines, including Klonopin. Some people, however, appear to have particular difficulty in switching from Klonopin to diazepam. In such cases it is possible to have special capsules made up containing small doses, e.g. an eighth or a sixteenth of a milligram or less, which can be used to make gradual dosage reductions straight from Klonopin. These capsules require a doctor's prescription and can be made up by hospital pharmacists and some chemists in the UK, and by compounding pharmacists in North America. A similar technique can be used for those on other benzodiazepines who find it hard to substitute diazepam. To locate a compounding pharmacist in the USA or Canada this web site may be useful: www.iacprx.org. Care must be taken to ensure that the compounding pharmacist can guarantee the same formula on each prescription renewal. It should be noted, however, that this approach to benzodiazepine withdrawal can be troublesome and is not recommended for general use.

(3) Designing and following the withdrawal schedule

Some examples of withdrawal schedules are given on later pages. Most of them are actual schedules which have been used and found to work by real people who withdrew successfully. But each schedule must be tailored to individual needs; no two schedules are necessarily the same. Below is a summary of points to consider when drawing up your own schedule.

1. Design the schedule around your own symptoms. For example, if insomnia is a major problem, take most of your dosage at bedtime; if getting out of the house in the morning is a difficulty, take some of the dose first thing (but not a large enough dose to make you sleepy or incompetent at driving!).

2. When switching over to diazepam, substitute one dose at a time, usually starting with the evening or night-time dose, then replace the other doses, one by one, at intervals of a few days or a week. Unless you are starting from very large doses, there is no need to aim for a reduction at this stage; simply aim for an approximately equivalent dosage. When you have done this, you can start reducing the diazepam slowly. If, however, you are on a high dose, such as 6mg alprazolam (equivalent to 120mg diazepam), you may need to undertake some reduction while switching over, and may need to switch only part of the dosage at a time (see Schedule 1). The aim is to find a dose of diazepam which largely prevents withdrawal symptoms but is not so excessive as to make you sleepy.

3. Diazepam is very slowly eliminated and needs only, at most, twice daily administration to achieve smooth blood concentrations. If you are taking benzodiazepines three or four times a day it is advisable to space out your dosage to twice daily once you are on diazepam. The less often you take tablets the less your day will revolve around your medication.

4. The larger the dose you are taking initially, the greater the size of each dose reduction can be. You could aim at reducing dosage by up to one tenth at each decrement. For example, if you are taking 40mg diazepam equivalent you could reduce at first by 2-4mg every week or two. When you are down to 20mg, reductions could be 1-2mg weekly or fortnightly. When you are down to 10mg, 1mg reductions are probably indicated. From 5mg diazepam some people prefer to reduce by 0.5mg every week or two.

5. There is no need to draw up your withdrawal schedule right up to the end. It is usually sensible to plan the first few weeks and then review and if necessary amend your schedule according to your progress. Prepare your doctor to be flexible and to be ready for your schedule to be adjusted to a slower (or faster) pace at any time.

6. As far as possible, never go backwards. You can stand still at a certain stage in your schedule and have a vacation from further withdrawal for a few weeks if circumstances change (if for instance there is a family crisis), but try to avoid ever increasing the dosage again. You don't want to back over ground you have already covered.

7. Avoid taking extra tablets in times of stress. Learn to gain control over your symptoms. This will give you extra confidence that you can cope without benzodiazepines (see Chapter III, Withdrawal Symptoms).

8. Avoid compensating for benzodiazepines by increasing your intake of alcohol, cannabis or non-prescription drugs. Occasionally your doctor may suggest other drugs for particular symptoms (see Chapter III, Withdrawal Symptoms), but do not take the sleeping tablets zolpidem (Ambien), zopiclone (Zimovane, Imovane) or zaleplon (Sonata) as they have the same actions as benzodiazepines.

9. Getting off the last tablet: Stopping the last few milligrams is often viewed as particularly difficult. This is mainly due to fear of how you will cope without any drug at all. In fact, the final parting is surprisingly easy. People are usually delighted by the new sense of freedom gained. In any case the 1mg or 0.5mg diazepam per day which you are taking at the end of your schedule is having little effect apart from keeping the dependence going. Do not be tempted to spin out the withdrawal to a ridiculously slow rate towards the end (such as 0.25mg each month). Take the plunge when you reach 0.5mg daily; full recovery cannot begin until you have got off your tablets completely. Some people after completing withdrawal like to carry around a few tablets with them for security "just in case", but find that they rarely if ever use them.

10. Do not become obsessed with your withdrawal schedule. Let it just become a normal way of life for the next few months. Okay, you are withdrawing from your benzodiazepines; so are many others. It's no big deal.

11. If for any reason you do not (or did not) succeed at your first attempt at benzodiazepine withdrawal, you can always try again. They say that most smokers make 7 or 8 attempts before they finally give up cigarettes. The good news is that most long-term benzodiazepine users are successful after the first attempt. Those who need a second try have usually been withdrawn too quickly the first time. A slow and steady benzodiazepine withdrawal, with you in control, is nearly always successful.

(4) Withdrawal in older people

Older people can withdraw from benzodiazepines as successfully as younger people, even if they have taken the drugs for years. A recent trial with an elderly population of 273 general practice patients on long-term (mean 15 years) benzodiazepines showed that voluntary dosage reduction and total withdrawal of benzodiazepines was accompanied by better sleep, improvement in psychological and physical health and fewer visits to doctors. These findings have been repeated in several other studies of elderly patients taking benzodiazepines long-term.

There are particularly compelling reasons why older people should withdraw from benzodiazepines since, as age advances, they become more prone to falls and fractures, confusion, memory loss and psychiatric problems (see Chapter 1).

Methods of benzodiazepine withdrawal in older people are similar to those recommended above for younger adults. A slow tapering regimen, in my experience, is easily tolerated, even by people in their 80s who have taken benzodiazepines for 20 or more years. The schedule may include the use of liquid preparations if available and judicious stepwise substitution with diazepam (Valium) if necessary. There is, of course, a great deal of variation in the age at which individuals become "older" - perhaps 65-70 years would fit the definition in most cases.

(5) Antidepressants

Many people taking benzodiazepines long-term have also been prescribed antidepressant drugs because of developing depression, either during chronic use or during withdrawal. Antidepressant drugs should also be tapered slowly since they too can cause a withdrawal reaction (euphemistically labelled "antidepressant discontinuation reaction" by psychiatrists). If you are taking an antidepressant drug as well as a benzodiazepine it is best to complete the benzodiazepine withdrawal before starting to taper the antidepressant. A list of antidepressant drugs and brief advice on how to taper them is given in Schedule 13 of this chapter. Some antidepressant withdrawal ("discontinuation") symptoms are shown in Chapter III (Table 2).

The above summary applies to people who are planning to manage their own withdrawal - probably the majority of readers. Those who have the help of a knowledgeable and understanding doctor or counsellor may wish to share the burden somewhat. In my withdrawal clinic I used usually to draw up a draft schedule which I discussed with each patient. Most patients took a close interest in the schedule and suggested amendments from time to time. However, there were some who preferred not to think about the details too much but simply to follow the schedule rigidly to the end. This group was equally successful. A very few (probably about 20 patients out of 300) wished to know nothing about the schedule, but just to follow instructions; some of these also entered a clinical trial of withdrawal. For this group (with their consent or by their own request), dummy tablets were gradually substituted for the benzodiazepines. This method was also successful and at the end of the process the patients were amazed and delighted when they found they had been off benzodiazepines and taking only dummy tablets for the last 4 weeks. There are more ways than one of killing a cat, as they say!

FURTHER READING

• Ashton, H. (1994) The treatment of benzodiazepine dependence. Addiction 89;1535-1541.

• Trickett, S. (1998) Coming off Tranquillisers, Sleeping Pills and Antidepressants. Thorsons, London.