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Guidance on Benzodiazepines:
Prescribing and Management of Dependence in
Substance Misuse Treatment Services
Approved
Version
Date of First Issue
Review Date
Date of Issue
EQIA
Author / Contact
09/05/2013
8
01/03/2011
09/05/2014
09/05/2013
Yes / No
Dr Fiona Morrison
Group / Committee
– Final Approval
FV Area Drug & Therapeutics Committee
04/03/2011
This document can, on request, be made available in alternative formats
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NHS Forth Valley
Consultation and Change Record
Contributing Authors:
Dr Fiona Morrison, Dr Claire McIntosh, Graham Nisbet,
Valerie Kippen, Denise Neary, Calum Blair
Consultation Process:
Substance Misuse Integrated Governance Group: Prescribing
Subgroup
Primary Care Drug & Therapeutics Committee
Area Drug & Therapeutics Committee
Distribution:
NHS Forth Valley Substance Misuse Prescribing Services
Quality Improvement website
Change Record
Date
Author
Change
Version
July 2010
FM
Change to new guideline format and update of
appendix details & minor amendments
V7
March 2012
FM
Update of references, minor amendments and
addition of monitoring sheet
V8
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Contents
Page
Introduction
4
What do benzodiazepines do in the body?
5
The evidence base for management of benzodiazepine addiction
7
Acute Withdrawal symptoms
8
Protracted Withdrawal Symptoms
9
Approximate dose equivalent to 5mg diazepam
10
Managing patients with persistent benzodiazepine misuse
12
Indications for benzodiazepine prescription
13
Procedure for benzodiazepine reduction package
14
Appendix 1 – Pre-prescription Drug Diary
15
Appendix 2 – CIWA-B Form
16
Appendix 3 – Benzodiazepine Prescribing Agreement
19
Appendix 4 – Prescription monitoring record
20
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Introduction
It has become apparent to both medical and keyworking staff that there are an
increasing number of patients who continue to misuse benzodiazepines despite
refraining from illicit opiate usage when maintained on an adequate dose of opiate
substitution treatment (Phase 2 of MAT/BAT).
There are limited methods of monitoring compliance with treatment for
benzodiazepine dependence, meaning that some patients could continue to abuse
street sources of benzodiazepines in addition to their prescribed ‘reducing’ course of
benzodiazepine medication.
Clinical experience of team members and a
subsequent audit indicate that the majority of patients do not achieve abstinence
from benzodiazepines following this treatment regime.
The purpose of this guide is to aid keyworkers to identify and manage those patients
who persistently use benzodiazepines in addition to their opiate substitution
treatment. It is also intended to assist in determining which patients could benefit
from a reduction prescription package, and how this should be delivered.
Benzodiazepine dependence has been recognised for many years, with two distinct
clinical populations – therapeutic and non-therapeutic.


Therapeutic type is dependence on prescribed medication. The dose is
usually within the normal therapeutic range.
Non-therapeutic dependence is seen more commonly in polydrug abuse, with
often high doses as part of the addiction subculture.
Scope
This guidance applies to staff working within Specialist Substance Misuse Services
including: Community Alcohol & Drug Service (CADS), FV Criminal Justice Drug
Treatment Service (FVCJDTS) and Addiction Recovery Services (ARS).
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What do benzodiazepines do in the body?
Benzodiazepines were introduced in the 1960s as a preferred alternative to
barbiturates for anxiety and insomnia but over the following three decades addiction
problems were recognised. Recent studies have shown that up to 90% of people
attending addiction treatment centres had utilised benzodiazepines illicitly within a
twelve-month period of which approximately half had used them intravenously.
Benzodiazepines display five major therapeutic effects irrespective of their marketed
indication. These actions are virtually the same for all benzodiazepines regardless of
their potency, speed of elimination or duration of effects.
Action
Anxiolytic (relief of anxiety)
Hypnotic (promotes sleep)
Myorelaxant (relaxes muscles)
Anticonvulsant (stop fits)
Amnesia (short-term memory)
Clinical Use
Anxiety/Panic disorder, phobia
Insomnia
Spastic disorders, muscle spasm
Epilepsy, seizures
Pre-med, sedation for minor ops
As demonstrated above benzodiazepines can be valuable, indeed in some
circumstances life saving, across a varied spectrum of clinical conditions. Nearly all
of the adverse effects are as a consequence of long-term use and in 1988 the UK
Committee on Safety of Medicines recommended that benzodiazepines should be
reserved for short-term use (2-4 weeks) only.
At a chemical level, benzodiazepines work by enhancing a natural brain chemical,
GABA (gamma-aminobutyric acid). GABA is a neurotransmitter (transmits messages
from one neuron to another) that is inhibitory in action – it tells neurons that it
contacts to slow down or “stop firing”. Considering that 40% of the brain’s neurons
respond to GABA, this means that GABA has a generalised quietening influence on
the brain. This natural effect is augmented by benzodiazepines causing an extra
(often excessive) slowing down of neurons.
These chemical influences can lead to the adverse effects of benzodiazepines as
listed below:
1. Over-sedation. A dose-related extension of the sedative effects of
benzodiazepines. May include drowsiness, poor concentration, confusion,
weakness and dizziness. Can be seen as a “hangover” effect in those taking
benzodiazepines at night. Tolerance to the sedative effects of benzodiazepines
usually develops over a couple of weeks and rarely do patients complain of
sleepiness although fine judgement and some memory functions may still be
impaired.
2. Drug Interactions. Benzodiazepines interact with a multitude of other drugs with
sedative properties, which importantly includes alcohol. If sedative drugs are
taken in overdose, benzodiazepines may add to the risk of fatality.
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3. Memory Impairment. Continued use of benzodiazepines on a prolonged basis
can lead to an inhibition of learning (formation of new memories) in addition to
the “episodic memory” lapses described earlier (e.g. as when used
preoperatively). The episodic memory lapses are possibly implicated in
behaviours such as shoplifting, etc.
4. Paradoxical Stimulant Effects. Occasionally a stimulant effect with increased
anxiety, excitability, irritability and violent behaviour being seen can occur. More
commonly friends or relatives comment on an increase in argumentative nature.
5. Depression, Emotional Blunting. As with people who have alcohol dependence
problems, long-term benzodiazepine users are often depressed. “Emotional
anaesthesia” is a common complaint where patients feel unable to experience
pleasure or pain.
6. “Floppy baby syndrome”. Benzodiazepines can cross the placenta and can result
in failure to suckle and over sedation in the neonate.
Tolerance to many of the effects of benzodiazepines develops with regular use.



to the hypnotic effects develops rapidly and sleep studies have shown that
sleep patterns return to pre-treatment levels after only a few weeks of regular
benzodiazepine use.
to the anxiolytic effects develops more slowly but after a few months there is
little evidence to suggest that they remain effective for this purpose.
to anticonvulsant effects similarly develops over a few months making them
unsuitable for long-term control of epilepsy.
Dependence (psychological or physical) can develop over a few weeks or months
and is demonstrated by individuals showing several of the following characteristics:
a) They have taken benzodiazepines for months or years
b) They gradually start to “need” benzodiazepines to perform normal daily
activities
c) They have difficulty stopping or reducing the drug because of withdrawal
symptoms
d) Benzodiazepine use has continued although the original indication for
prescription has disappeared
e) They contact their doctor regularly to try to obtain repeat prescriptions
f) The total daily dose taken has increased since first taking the drug
g) They often have increased physical and psychological complaints (anxiety,
insomnia) despite continuing to take benzodiazepines
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The evidence base for managing benzodiazepine abuse and dependence
Review of the literature on management of benzodiazepine abuse and/or
dependence yields very little objective evidence as to how this issue should be dealt
with. Consistent with this point, Professor C. Heather Ashton of the Division of
Psychiatry, University of Newcastle, probably one of Britain’s foremost authorities on
benzodiazepine dependence, has concluded:
‘’Longer term outpatient management of benzodiazepine abusers is
problematic…….However the overwhelming advice is that it is generally
inadvisable to prescribe benzodiazepines as maintenance treatment for drug
misusers or alcoholics…. Nevertheless it is clear that many benzodiazepine
abusers, like prescribed users, suffer from anxiety, insomnia and depression.
It may be that a flexible, individually tailored approach to benzodiazepine and
other psychotropic drug prescribing as well as psychological methods where
practical, carried out in specialist centres, would bring the best results.
Unfortunately, in the present climate the rate of relapse after short-term
benzodiazepine detoxification may be as high as it is with opiate detoxification
(i.e. over 90% after one year), and further experience is needed to establish
the optimal long-term management. Meanwhile efforts to reduce inappropriate
prescribing of benzodiazepines both in general practice and in hospital may
help decrease the quantity of benzodiazepines at present spilling into the illicit
drug market.’’(www.benzo.org.uk/ashbzab.htm first published in Drugs and
Dependence pp. 197-212, Harwood Academic Publishers (2002)
The only generally agreed point that is supported by most experts in the addictions
field and backed up by scientific research is that patients who use high doses of
benzodiazepines (diazepam 30mg or equivalent) on a regular basis are at risk of
permanent cognitive impairment.
Many authors have used various types of prescribed benzodiazepine reduction
protocols, but no trials have demonstrated the superior efficacy of any particular
regimen over other suggested models.
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Acute Withdrawal Symptoms
Patients may complain of a whole variety of withdrawal symptoms related to
cessation of benzodiazepines many of which are predictable. The majority of acute
symptoms are anxiety related which may present as psychological symptoms or
physical symptoms (e.g. exacerbation of underlying irritable bowel syndrome).
The most effective way to deal with these symptoms is by explaining to patients that
these symptoms are typical of benzodiazepine withdrawal and offering alternative
relaxation methods (Behaviour therapy, CBT) and/or complementary treatments
such as aromatherapy or acupuncture.
Undertaking the CIWA-B assessment, which is explained later in this document, can
perform a more objective assessment.
Although this list is not exhaustive, a selection of acute symptoms the clients may
report is given below:
Palpitations
Shortness of breath
Headaches
“Butterflies” in stomach
Flushing
Shakiness
Difficulty swallowing
Poor sleep
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Racing heart beat
Faintness
Chest pain
Muscle aches
Nausea
“Jelly” legs
Sensation of choking
Tiredness/exhaustion
Numbness
Dizziness
Stomach pain
Sweating
Pins and needles
Bowel/bladder problems
Changes in appetite
Poor concentration
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Protracted Withdrawal Symptoms
A minority of patients (10 - 15%) who have successfully withdrawn from
benzodiazepines seem to suffer from long-term effects that may take months or
even years to resolve. The reasons why these symptoms persist in some individuals
remain unclear.
The table below shows the symptoms most likely to be persistent along with the
usual course followed:
Symptoms
Usual Course
Anxiety
Gradually diminishes over 1 year
Depression
May last a few months; Responds to
antidepressant drugs
Insomnia
Gradually
months
Sensory Symptoms (tingling,
numbness, tinnitus, etc)
Gradually recedes but may last at
least a year and occasionally several
years
Motor Symptoms (Pain, weakness,
spasms, jerks, etc)
Gradually recedes but may last at
least a year and occasionally several
years
Poor Memory and Cognition
Gradually recedes but may last at
least a year and occasionally several
years
Gastrointestinal Symptoms
Gradually recedes but may last at
least a year and occasionally several
years
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over
6-12
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Approximate dose equivalent to 5mg diazepam
Benzodiazepine
Trade Name
Dose equivalent to 5mg
diazepam
Alprazolam
Xanax®
0.25mg - 0.5mg
Chlordiazepoxide
Librium®
15mg
Clobazam
Frisium®
10mg
Clonazepam
Rivotril®
0.5mg – 1mg
Diazepam
Valium®
5mg
Flunitrazepam
Rohypnol®
0.5mg
Flurazepam
Dalmane®
7.5mg -15mg
Loprazolam
Dormonoct®
0.5mg – 1mg
Lorazepam
Ativan®
0.5mg – 1mg
Lormetazepam
Nitrazepam
0.5mg – 1mg
Mogadon®
5mg
Oxazepam
15mg
Temazepam
10mg
Triazolam
Halcion®
0.25mg
Zaleplon *
Sonata®
10mg
Zolpidem *
Stilnoct®
10mg
Zopiclone *
Zimovane®
7.5mg
Approximate dosages of common benzodiazepines and Z-drugs equivalent to 5mg
diazepam.
* These drugs are chemically different from benzodiazepines but have the same
effects on the body and act by the same mechanisms.
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Although the majority of patients who misuse benzodiazepines will be accessing
diazepam there are a number of other benzodiazepines which may be used as an
alternative or in addition to diazepam.
When negotiating a structured reduction programme with a patient it is often useful
to calculate the total quantity of benzodiazepines used as an equivalent dose of
diazepam so that an agreed baseline level of use can be determined from which to
commence reduction
From the conversion chart, it should be possible to calculate the total dose of
benzodiazepine used by the patient as an equivalent total dose of diazepam.
From Maudsley: ‘The half-lives of benzodiazepines vary greatly. The degree of
sedation that they induce also varies, making it difficult to determine exact
equivalents.
Extra precautions apply in patients with hepatic dysfunction, as
diazepam and other long-acting drugs may accumulate to toxic levels. Diazepam
substitution may not be appropriate in this group of patients.’
References
1.
2.
3.
4.
British National Formulary No. 64. September 2012
The Maudsley Prescribing Guidelines, 11th edition. 2012
Bazire Psychotropic Drug Directory. 2010
Martindale: The Complete Drug Reference, Pharmaceutical Press. 37th
edition. 2011
5. Department of Health (England) and the devolved administrations. Drug
misuse and dependence: UK Clinical Guidelines on Clinical Management.
London: Department of Health (England), the Scottish Government, Welsh
Assembly Government and Northern Ireland Executive. 2007
www.dh.gov.uk/publications.
6. Ashton, C.H. Benzodiazepines: How they work and how to withdraw (aka The
Ashton Manual) 2002, Chp II, available at
http://www.benzo.org.uk/bzmono.htm (accessed 29.03.2012).
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Managing patients with persistent benzodiazepine misuse
From the preceding information it is clear that it remains undesirable for patients to
continue to misuse benzodiazepines (BZDs) on a prolonged basis, but it is also
patently clear that achieving a successful reduction programme is a difficult
challenge.
The first challenge is to decide at what point in the patient’s progress through
MAT/BAT is likely to be the most successful or effective time to work with the patient
in eliminating benzodiazepine use from their routine. Recent experience suggests
that this is not likely to be when a patient enters an opiate substitution treatment.
Rather we suggest that tackling benzodiazepine use is more realistic when a patient
is refraining from opiate substances on a satisfactory dose of
methadone/buprenorphine (Phase 2 of MAT/BAT). During this phase, some patients
may spontaneously reduce their BZD use once they are stabilised on an optimal
maintenance dose of methadone. However, others will require ongoing keyworker
input in order to try reduce use. Keyworkers should use the Anxiety Management
Keyworker Manual to assist them with this work.
A full assessment of use and symptoms should be made following Section 2 of the
keyworker manual (pages 10-17). Thereafter a formulation of the issues should be
made (Section 3) and discussed with the patient. A plan of intervention can then be
agreed. Section 4 of the manual sets out interventions likely to assist both
keyworker and patient to achieve the set goals.
Rather than initiate a prescription for a diazepam reduction, patients should be
advised by their keyworker to reduce and/or cease their own BZD use.
The reason we do not advocate the provision of a prescription of diazepam at this
point in time for most patients is twofold:
1) Unless dispensed doses of diazepam can be supervised or other safety
arrangements put in place, it is unlikely that a prescription for reducing doses
of diazepam is going to effectively replace the usually much higher doses of
BZD abused by the patient. At worst, the prescribed course of diazepam does
little more than supplement the patient’s usual supply of BZD.
2) As well, it has been our observation that many patients accept a reducing
prescription for diazepam not because they are ready or motivated to cease
BZDs but because if they cannot get a maintenance prescription from the
service, a reducing prescription is ‘better than nothing’.
However, in some cases, a BZD prescription may be indicated.
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Indications for a benzodiazepine prescription
The decision to prescribe benzodiazepines should never be undertaken lightly and
should only be part of a detoxification process.
Indications for a reduction prescription include:




Patients on a long term prescription at entry into a Substance Misuse
Treatment service.
Patients with alcohol dependence who require medical detoxification
Patients with drug dependence and severe psychiatric disorders
Patients stabilised on opiate substitution therapy with a history of moderate or
severe benzodiazepine dependence syndrome (where attempts to cease use
without prescription have failed)
It is important to create the right culture of expectation.
It is at this point we need to estimate the total daily dose of benzodiazepines used by
the patient, which can then be converted to an equivalent dose of diazepam to give
a starting point for reduction. This can be achieved by a patient undertaking a
recording diary of benzodiazepine use for a period of a couple of weeks.
There is no evidence-based schedule for dose reduction of benzodiazepines. There
will need to be negotiation between the keyworker and the patient to find a mutually
agreeable and realistic regime that will aim to achieve elimination of
benzodiazepines from the individual’s routine within an acceptable time scale. The
keyworker should bear in mind from the limited evidence above that it is desirable to
try to reduce down to a dose of diazepam 30mg daily (or equivalent) as soon as
possible due to possible cognitive impairment at doses higher than this. A reduction
prescription will not normally exceed diazepam 30mg
On agreeing a reduction regime it is useful to monitor this objectively by the patient
completing a benzodiazepine withdrawal diary. The keyworker should complete the
planned doses as agreed with the patient prior to the end of the consultation, and
over the following four weeks the patient should complete what doses were actually
taken along with any other substances and subjective discomfort. (Appendix 1)
On reviewing the patient after four weeks the keyworker should carry out a CIWA-B
(Clinical Institute Withdrawal Assessment for Benzodiazepines) score to measure
withdrawals. (Appendix 2). Following this assessment the keyworker and patient can
again negotiate an agreed plan for reduction over the following four weeks and
repeat the process as above.
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Procedure for benzodiazepine reduction package
Assessment and
diary work
Formulation of
Issues in care plan
Discussion at
Team Meeting (agree
starting dose)
patient agreement
and care plan
completed
Review of Progress
(CIWA-B, Diary and
Care Plan)
Step-wise
reductions in dose
with review of
progress (as above)
until zero
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DRUG DIARY
DAY/DATE
TIME
Patient’s Name:
What did you use and
how did you use it?
CHI No.
How much did
you use?
Where did you use?
Monday
Tuesday
Wednesday
Thursday
Friday
Saturday
Sunday
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Appendix 1
Who did you use with?
Why did you use?
WEEK BEGINNING……………………………………………………….
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Appendix 2
CIWA-B
NAME
Dob
Address
For each of the following items, please circle the number which best describes the severity of each
symptom or sign
1
Observe behaviour for restlessness and agitation
0
1
2
3
4
2
Restless
Paces Back and forth, unable to sit still
Ask patient to extend arms with fingers apart, observe tremor
0
1
2
3
4
3
Home, normal activity
No tremor
Not visible, can be felt in fingers
Visible but mild
Moderate with areas extended
Severe, with arms not extended
Observe for sweating, feel palms
0
1
2
3
4
No sweating visible
Barely perceptible sweating, palms moist
Palms and forehead moist, reports armpit sweating
Beads of sweat on forehead
Severe drenching sweats
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For each of the following items, ask the patient to circle the number which best describes how
he/she feels
4
Do you feel irritible?
Not at all
0
1
2
3
Very much so
4
5
Do you feel fatigued?
Not at all
0
1
2
3
Severely
4
6
Do you feel tense?
Not at all
0
1
2
3
Very much so
4
7
Do you have difficulties
concentrating?
8
Do you have any loss of
appetite?
9
Have you any
numbness or burning
sensation on you face,
hand or feet?
10
Do you feel your heart
racing?
11
Does your head feel full
or achy?
12
Do you feel muscle
aches or stiffness?
13
Do you feel anxious,
nervous or jittery?
14
Do you feel upset?
No difficulty
0
Can't concentrate
1
2
3
No loss
0
No appetite
1
2
3
No
0
1
2
3
1
2
3
1
2
3
4
Severe
1
2
3
Not at all
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4
Severe
Not at all
0
4
Constantly
No
0
4
Severe
No
0
4
4
Very much so
0
1
2
3
4
Not at all
0
1
2
3
Very much so
4
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Very restful
15
How restful was your
sleep last night?
16
Do you feel weak?
17
Do you think you didn't
have enough sleep last
night?
18
Do you have any visual
disturbances?
(sensetivity to light,
blurred vision)
19
Are you fearful?
20
Have you been worrying
about possible
misfortunes lately?
Very much so
0
1
2
3
4
Not at all
0
1
2
3
Very much so
4
No
0
Not nearly enough
1
2
3
Not at all
0
Not at all
0
Yes extreme
1
1
2
2
3
4
3
Very much so
4
Not at all
0
4
Very much so
1
2
3
4
Total Score
(Total of Items 1 to 20)
Use these scores to monitor trends in the
patient's condition
Rater's Initials
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Appendix 3
Benzodiazepine Prescribing Agreement
Name ...................................................................................................................................
Date of birth .................................................................
As part of my treatment plan which includes prescribing diazepam I agree to the
following conditions:1.
I am currently taking _____mg of diazepam (or equivalent) daily
2.
I agree to participate in the full care package as outlined in my
medical record.
3.
If I do not adhere to the agreed care package, I accept that my
prescribed benzodiazepines may be reduced or stopped.
4.
I acknowledge that
benzodiazepines.
5.
If I present intoxicated as assessed by clinical staff, I accept that
my prescribed benzodiazepines may be reduced or stopped.
6.
I agree not to sell or otherwise dispose of medication prescribed to
me
7.
I agree to the tablets being dispensed daily initially.
8.
I understand that the maximum starting dose will usually be 30mg.
9.
I accept that this benzodiazepine prescription is part of a reduction
schedule as outlined in the service Guidance on Benzodiazepines.
10.
I understand that lost tablets cannot be replaced.
11.
The service will adhere to the NHS Forth Valley Guidance on
Benzodiazepines in Substance Misuse Treatment Services.
I
should
not
take
any
additional
Signed..................................................................................................................................
Witnessed ............................................................................................................................
Date .............................................................................
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Appendix 4
Prescription Monitoring Record
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Publications in Alternative Formats
NHS Forth Valley is happy to consider requests for publications in other
language or formats such as large print.
To request another language for a patient, please contact 01786 434784.
For other formats contact 01324 590886,
text 07990 690605,
fax 01324 590867 or
e-mail - fv-uhb.nhsfv-alternativeformats@nhs.net
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