Benzodiazepines and Your Patients:
A Management Programme

by
Roche Products (UK) Ltd
ca. 1990

THE PRESCRIBING OF & WITHDRAWAL
FROM BENZODIAZEPINES

[Note: This document was issued by Roche to prescribing physicians in the UK upon request.
Views, equivalencies, tapering and withdrawal advice given in this document are not necessarily
endorsed by the owner of this site and it is reproduced here for information purposes only.]

When should you prescribe benzodiazepines?

There is no doubt that benzodiazepines have been of considerable benefit in the treatment of anxiety, insomnia, muscle spasm and epilepsy. However, there is increasing concern, both among doctors and the lay public regarding the potential for dependence on this group of drugs.

Benzodiazepines are the most commonly used anxiolytics and hypnotics. The prescriber must fully appreciate the differences in these indications since most anxiolytics will induce sleep when given in large doses at night and most hypnotics will sedate when given in divided doses during the day.

INSOMNIA

The cause of the insomnia should be established and where possible the underlying factors should be treated. Insomnia can be divided into different types as outlined in the British National Formulary.

Transient Insomnia

Transient insomnia may be due to a change in working pattern, jet lag, a noisy environment or some other extraneous and transient factor which will disappear in time. In these circumstances it may be desirable to prescribe for a few doses only, although assurance to the patient may be all that is required.

Short Term Insomnia

Short term insomnia is usually related to an emotional problem but sometimes to a serious medical condition.

Chronic Insomnia

Common causes of chronic insomnia will include psychiatric disorders such as anxiety, depression and drug and alcohol abuse. Other causes will include painful conditions such as arthritis and Parkinson's disease, pruritis, dyspnoea and nocturia.

Clearly it is desirable to establish the cause of the insomnia and treat this which, in many cases, will render the prescription of a hypnotic unnecessary. Indeed chronic insomnia can be worsened by the injudicious prescription of hypnotics.

Before resorting to the prescription of hypnotics it is also important to pay attention to the sleeping environment of the patients.

Many factors can affect a night's sleep and attention should be given to this (1):

1. Rise at a regular time in the morning, even after bad nights. This may strengthen the circadian rhythmicity of sleep and wakefulness, and lead to a more regular time of sleep onset.

2. Sleep adequately but not excessively. Excessively long times in bed may lead to fragmented and shallow sleep.

3. Take regular exercise during the day. Regular exercise encourages sound sleep, but occasional bouts of exercise do not.

4. Keep a comfortably cool room. A hot room disturbs sleep, though a cold room does not help to deepen sleep.

5. Do not go to bed hungry. A light bedtime snack, e.g. a warm milk drink, helps many people to sleep soundly.

6. Ensure a quiet bedroom. Occasional loud noises disturb sleep even if the subject has no recollection of waking. Soundproofed windows may be helpful.

7. Avoid caffeine. Coffee and tea lighten sleep, even in people who claim to be unaffected.

8. Avoid too much alcohol. Alcohol helps people fall asleep but the ensuing sleep is fragmented.

9. Do not try too hard. If sleep does not come easily get up and do something for an hour.

10. Use sleeping pills only exceptionally. The occasional use of hypnotics is justified to overcome an acute problem, but continued use should be avoided.

There are many different hygiene factors which may help an individual sleep without the necessity of hypnotics. When a benzodiazepine is necessary the Royal College of Psychiatrists (2) and the C.S.M. have issued advice on their use. The recommendations of the Royal College of Psychiatrists are outlined here:

Insomnia

1. disabling,

2. severe, or

3. subjecting the individual to extreme distress.

 

Benzodiazepines for sleep induction should ideally be given only intermittently either in in-patient or out-patient settings. As much care must be taken in the prescribing of benzodiazepines for insomnia as for anxiety.

There has been in the past an automatic assumption that benzodiazepines should be given for sleep disturbance. It is extremely important that doctors should look at the underlying causes for insomnia before deciding upon the use of drugs for symptomatic relief. If benzodiazepines are prescribed for insomnia, then this should be at a low dosage, not every night, and normally for a maximum period of one month.

ANXIETY

Anxiety is the final common pathway for different intrapsychic and biochemical processes. It is essential to remember this for benzodiazepines will affect the final common pathway and thus in the immediate short term help many anxious patients, but have no effect on the cause of their anxiety. Indeed benzodiazepines may mask important signs and symptoms and ultimately make treatment more difficult.

In the past there has been a tendency to prescribe benzodiazepines to patients with stress related symptoms, unhappiness and minor physical disease. (3) Their use in many of these circumstances is not justified. Even in more severe cases requiring drug therapy, diagnostic difficulties are encountered in the management of anxiety and these are most likely to occur when: (4)

	the primary complaint is a physical symptom rather than anxious mood e.g. palpitation, change in bowel function.
	the anxiety neurosis gives rise to a secondary condition e.g. depression secondary to anxiety, alcohol dependence secondary to anxiety.
	the anxiety symptoms are the presenting feature of an organic illness e.g. thyrotoxicosis, phaechromocytoma, temporal lobe epilepsy.

When a clear diagnosis has been made, the treatment of anxiety is similar to that of insomnia and involves many non-drug options such as:

1. Listening and talking.

2. Simple psychotherapy

3. Relaxation training.

4. Behaviour and cognitive therapy

When benzodiazepines are to be used in the treatment of anxiety the recommendations of the Royal College of Psychiatrists (2) and the C.S.M. are outlined here:

Benzodiazepines should be primarily prescribed for the short-term relief of anxiety when it is:

Anxiety

1. disabling,

2. severe, or

3. subjecting the individual to extreme distress.

In the above cases, benzodiazepines ideally should be prescribed for no more than one month.

Benzodiazepines may be prescribed where anxiety is complicated by other illnesses, but caution should be used in prescribing them when the disorder is already chronic. The long-term use of any compound to deal with mild anxiety is not in general advised. The consequences of long-term usage are liable to far outweigh the symptomatic relief.

There is not sufficient evidence to support the use of benzodiazepines for obsessional states.

When prescribing for either insomnia or anxiety it is important to be familiar with the appropriate data sheet(s) for the benzodiazepine(s) of your choice. It is also important to stress the risk of therapy as well as the benefits and to stress the short-term nature of this drug treatment.

Recognising a benzodiazepine-dependent patient

When dependence develops during prolonged continuous use of benzodiazepines, it is usually possible for the GP to recognise its existence and distinguish it from inadequately treated chronic anxiety or insomnia. Some important points are:

Patient Characteristics

There are individual patient characteristics which may predispose certain patients to become dependent on benzodiazepines, such as history of inappropriate use of alcohol or other drugs of dependence. Rarely, a drug-seeking behaviour is seen.

Timing of return of symptoms on stopping benzodiazepines

Symptoms of anxiety or panic may occur within about one to three days, depending on the elimination half-life of the benzodiazepine and its accumulative metabolites, and normally peak in intensity at about five to seven days. This time sequence helps distinguish dependence from the return of an inadequately treated chronic anxiety (Figure 1).

 

Figure 1. A Comparison of the pattern of symptoms
with dependence (—) and return of anxiety (---). (5)

 

Should every 'dependent' patient be withdrawn?

There are categories of patients in whom withdrawal is inadvisable. The first group is those in whom withdrawal should not even be attempted, for instance, patients with a chronic physical disorder controlled by the benzodiazepine (epilepsy or spastic muscular disorders). In addition, there are some patients, particularly the elderly, where the problems caused by withdrawal outweigh the risks of continued long-term, low-dose treatment.

The second group consists of patients in whom attempts should be made at withdrawal, but whose quality of life is so improved during the use of benzodiazepines that long-term therapy (preferably intermittent fluctuating dosage) is justified medically.

This group includes people with severe chronic anxiety and insomnia and an inadequate personality who find it difficult to exist in society if not supported by therapy. It also includes the dependent personality who relapses to alcohol or other more dangerous drugs if therapy is withdrawn. In such cases it would be wise to conduct a case review of the patient with a colleague before continuing treatment.

Since the nature and extent of the disability changes in the second group, further periodic withdrawal attempts are desirable.

Attempts at withdrawal are more likely to succeed if the doctor, the relatives, and particularly the patient want to achieve complete withdrawal. In this context the use of a "verbal contract" may be worthwhile. If a patient is either negative or indifferent in their attitude to withdrawal, then a successful outcome is less likely.

How should withdrawal be achieved?

In-patient facilities are scarce and the majority of uncomplicated benzodiazepine-dependent patients can be withdrawn by their own general practitioner, using simple dose reduction. Referral is, in most cases, unnecessary and the majority of patients will not need the more complicated methods of withdrawal which will be outlined later in this booklet.

However, there are several circumstances in which the general practitioner should be wary about attempting withdrawal and in which specialist advice and help should be sought (Table II).

Difficulty over withdrawal and the intensity of the withdrawal reactions vary from one benzodiazepine to the other. In general, the longer a patient has taken a particular benzodiazepine, and the larger the dose, the greater the withdrawal problem may be.

It should be remembered that abrupt withdrawal should be avoided, and that a successful outcome and maintained abstinence is unlikely without adequate emotional support from the general practitioner, the family, and friends.

Methods for benzodiazepine withdrawal

Any benzodiazepine withdrawal programme should be carefully planned and structured, the aim being to gradually reduce to zero the amount of drug being taken.

There is no single best technique for withdrawal, but simple dose reduction is best for most patients. Equally there are no specific data relating to the rate of withdrawal or the total time involved. Nevertheless, whichever technique is used, the regimen must be discussed with the patient, and the goals must be simple and attainable.

Withdrawal can be achieved by many methods. Each involves regular supervision by the general practitioner. For example, the general practitioner can simply gradually reduce the daily dose of the patient's current benzodiazepine over a period of several weeks; or the general practitioner can switch the patient's short-acting benzodiazepine for a long-acting one before attempting withdrawal; alternatively, the withdrawal programme can be supplemented with concomitant therapy.

Listed below are four methods which follow the general structure discussed above· They should be regarded purely as guidelines; the exact withdrawal programme should be tailored to the individual's response due to the wide variation in subjective response.

Method 1

Gradual reduction in dosage

This is the simplest and most common method for withdrawing a benzodiazepine. For example, it is recommended that temazepam be gradually withdrawn taking 10mg for 2 weeks, 5mg for 2 weeks and then 2.5mg for 2 weeks. Some authorities feel, however, the method is more appropriate for long acting benzodiazepines, and for shorter acting compounds they would recommend method 2.

Method 2

Substitution (7)

1. Substitute the short-acting benzodiazepine with an approximately equivalent dose of a long-acting drug such as diazepam (see the dose equivalent below). Because of diazepam's long elimination half-life, the withdrawal symptoms appear to be less severe with little associated 'craving'. However, there may be a problem with daytime sedation (8) if the short-acting benzodiazepine was for night sedation.

2. Substitution should be gradual and the benzodiazepine replaced in increments of one dose per day. This can usually be accomplished within one week but should be tailored to the individual patient. Some patients require a higher dose than the approximate equivalent.

3. Once substitution is achieved, a gradual reduction of the diazepam dosage should follow. Diazepam is available in 2mg, 5mg and 10mg tablets, all of which can be halved, and in an elixir 2mg in 5ml, which can be diluted.

4. Stepwise reductions in dosage should be made every week or fortnight, or even monthly, depending upon the patient's response.

Suggested reductions are:

	Reduce by 2mg if daily dose 15mg to 20mg
	Reduce by 1mg if daily dose 10mg to 15mg
	Reduce by 0.5mg if daily dose 5mg

Tailor the dose reduction to patient response, ie weekly, fortnightly or monthly. Once patient is at a dosage of 0.5mg daily the dose interval can be increased to every two to three days.

Example

Replace the drug being used by equivalent doses of diazepam at the rate of one dose per day.