Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Introduction
Benzodiazepines are only licensed for maximum of 2 to 4 weeks and should only be used for short
term relief of anxiety that is severe, disabling, or causing the patient unacceptable distress, occurring
alone or in association with insomnia or short term psychosomatic, organic or psychotic illness.
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or causing the
patient extreme distress. The advice is similar for the non-benzodiazepine hypnotics: Zopiclone;
Zolpidem and Zalepon; which act as the benzodiazepine receptor.
The key concerns are that many people develop tolerance to the effects of hypnotics and gain little
benefit from chronic use.
Purpose
This guideline has been developed to promote best practice in prescribing hypnotics. It can be used
to support long term users in the safe withdrawal of these potentially addictive drugs. Safe, slow
withdrawal is important as withdrawal syndrome can occur causing side effects such as anxiety and
depression.
The British National Formulary and Committee on Safety of Medicines provide clear guidance on the
indications for these drugs. Changes in the controlled drug (CD) regulations recommend that
prescriptions for CDs should be limited to a quantity necessary for up to 30 days clinical need.
Negative Effects of Benzodiazepines
Adverse effects (which may also arise from short term use) include:







Drowsiness and falls (avoid hypnotics in older people as risk of fracture increases)
Impairment in judgement
Increased risks of experiencing a road traffic accident due to impaired judgement and
increased reaction time
Forgetfulness, confusion, irritability, aggression and excitability
Hangover effect the next morning after taking night time dose
Depression, reduced coping skills
Tolerance and dependence
- Tolerance to the hypnotic effects of benzodiazepines may be rapid and occur within
a few days or weeks of regular use
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Special Consideration should be given when prescribing in older patients because of
 Increased risk of bone fractures due to drowsiness and falls
 Declining renal function and changes to hepatic metabolism leads to increased sensitivity
and more pronounced adverse effects
 Consider the insomnia could be linked to arthritic pain or underlying depression
 Non drug therapies can help: Exercise programmes are likely to improve insomnia
Alternative Strategies for consideration before Initiating a Hypnotic




Avoid caffeine based drinks before going to bed
Psychological treatments including relaxation and counselling and cognitive behavioural
therapy as appropriate
Reassurance that sleep duration reduces as we get older and 5-6 hours is normal for older
people, especially if an individual ‘cat naps’ during the day
Treatment of underlying condition which may be causing/contributing to insomnia such as
pain; itching; dyspnoea; depression
New Prescriptions







Prescribe as an acute prescription only
Restrict prescriptions to a maximum 2 week course. Patients should be warned of side
effects and tolerance and advised to use every other night or, if necessary, a maximum of 5
nights continued use followed by a break.
Exercise caution when prescribing for older people
NICE have concluded that given the lack of compelling evidence to distinguish between the
z-hypnotics and the shorter acting benzodiazepine hypnotics, the drug with the lowest
purchase cost should be used in preference to more expensive alternatives. Choices:
Zopiclone or Temazepam (NB Temazepam available as liquid, Zopiclone is not and cannot be
crushed)
Patients who have not responded to one of these hypnotic drugs should not be prescribed
any of the others
Z-drugs must not be prescribed in pregnancy
For patients with mental health problems formulate a clear management plan
Existing Repeat Prescriptions


It is good practice to limit a quantity necessary for up to 30 days clinical need to improve
patient safety
Consider moving repeats to acute to monitor use
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Management of Hypnotic and Benzodiazepine Withdrawal
Risk Factors for poor withdrawal are:








History of previous severe withdrawal reaction, including withdrawal seizures
Patients on high dose e.g. more than 30mg diazepam equivalent daily for over 1 year
Duration of use
Older age or infirm condition
Lack of social support
History of drug or alcohol abuse
Concomitant severe medical or psychiatric illness including personality disorder
Patients with epilepsy who may have a greater risk of suffering from withdrawal seizures
Exemption Criteria
 Patients under the mental health services
 Pregnant patients
 Patients with more complex problems who have benzodiazepine dependence should be
considered for referral to the local special substance misuse team
General Principles



Ensure the patient is engaged and committed

Go slow! Physical withdrawal symptoms occur in about 40% of patients such as insomnia,
anxiety, loss of appetite, perspiration, tinnitus, perceptual disturbances (numbness, pins and
needles), vivid dreams, gastro-intestinal disturbance


Abrupt withdrawal can cause confusion, toxic psychosis

Warn patients that sleep may be disturbed before the normal rhythm is re-established and
that broken sleep and vivid dreams may persist

Reassurance and relaxation advice should be offered to deal with symptoms such as anxiety
management. Cognitive treatments or group therapy can help


Once reduced never increase dose again during a ‘bad patch’
Set realistic goals
The chances of success are improved if the patients: psychical; psychological and personal
circumstances are stable
Symptoms can occur within a few hours of stopping shorter acting drugs and up to several
weeks after stopping longer acting drugs. Symptoms may only appear after several dose
reductions
Monitor patients for potential abuse of alcohol and illicit drug use
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Suggested Withdrawal Plan for Benzodiazepines (see below for Z-drug withdrawal)
1) Transfer patient to equivalent daily dose of diazepam preferably taken at night if appropriate.
The diazepam dose may be prescribed in divided doses when the initial dose is high. Specialist
advice should be sought if a dose higher than diazepam 30mg/day seems necessary. Avoid
prescribing 10mg Diazepam tablets. (see table below)
2) Reduce diazepam dose in fortnightly steps as below; if withdrawal symptoms occur, maintain
this dose until symptoms remit
Doses greater than 20mg: Reduce daily dose by 2mg every 2 weeks
Doses less than 20mg:
Reduce daily dose by 1mg every 2 weeks until stopped.
3) Reduce dose in smaller fortnightly steps if necessary; it is preferable to reduce too slowly than
too quickly in patients who experience withdrawal difficulties
4) Stop completely; time needed for withdrawal can vary from about 4 weeks to a year or more
5) If patient experiences side effects withdrawing treatment, maintain at this dose until symptoms
improve. Slow withdrawal to every 4 weeks or longer depending on the individual.
Only issue quantity to cover until next review/appointment e.g. Number tablets taken daily x 14 days
Switching to diazepam is recommended for:
 People using the short-acting potent benzodiazepines (i.e. alprazolam and lorazepam)
 People using preparations that do not easily allow for small reductions in dose (i.e.
alprazolam, flurazepam, loprazolam and lormetazepam)
 People taking temazepam or nitrazepam who choose to withdraw from diazepam after
discussing the advantages and disadvantages
 People experiencing difficulty, or who are likely to experience difficulty, withdrawing directly
from temazepam, nitrazepam or Z-drugs, due to a high degree of dependency (associated
with long duration of treatment, high doses, and a history of anxiety problems).
Table 1 Showing dose equivalents for Diazepam and other Hypnotics
Approximate Equivalent Doses to Diazepam 5mg
Chlordiazepoxide
15mg
Nitrazepam
5mg
Loprazolam
0.5 – 1 mg
Oxazepam
15mg
Lorazepam
0.5mg
Temazepam
10mg
Lormetazepam
0.5 – 1 mg
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Z-Drug Withdrawal
There is little information available for withdrawal of these hypnotics if they have been used long
term. As they work similarly to benzodiazepines the same approach can be recommended for
withdrawing Z-drugs.
Withdrawing Zopiclone, Zolpidem or Zaleplon
1. Dosage should be withdrawn gradually on an individual basis
2. Reduce dose at two weekly intervals or slower
3. If patient experiences side effects while withdrawing treatment maintain at current dose until
symptoms improve, then slow withdrawal to every 4 weeks or longer depending on the
individual.
Example of withdrawal regimen
Dose
Number of tablets/day
Number of tablets/week
Starting Dose
Zopiclone 15mg
2x7.5mg
14 x 7.5mg
Stage 1 (2 weeks)
Zopiclone 11.25mg
1x7.5mg & 1x3.75mg
7 x 7.5mg & 7 x 3.75mg
Stage 2 (2 weeks)
Zopiclone 7.5mg
1x7.5mg
7x7.5mg
Stage 3(2 Weeks)
Zopiclone 3.75mg
1x3.75mg
7x3.75mg
Stage 4 (2 weeks)
Zopiclone 3.75mg
alternative nights
1x3.75mg every other
night
4x3.75mg
Stage 5
Stop
During withdrawal process:



Important to provide advice on good sleep hygiene and basic measures to reduce anxiety
If patients experience withdrawal effects encourage them to persevere, slow reduction and
suggest delaying next dose reduction. Do not revert to higher dosage
Reassure patient that if they experience difficulties they can contact the surgery for advice
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Audit - Targeting Patients
Information for GPs, Prescribing Advisors, Practice Based Medicine Co-ordinators










Search for patients on benzodiazepines (Nitrazepam, Flurazepam; Loprazolam;
Lormetazepam; Temazepam); Z-drugs Zopiclone (ZIMOVANE); Zolpidem (STILNOCT)
;Zaleplon (SONATA)). The practice may decide to split the searches into individual drugs to
make the work more manageable.
See exclusion criteria (see page 3), GP removes those patients who he/she feels
inappropriate to withdraw treatment from at this time (this should be reviewed 6 monthly)
GP/Prescribing advisor decides which patients are suitable for a telephone triage and those
who are suitable for face to face review
The practice may also decide to leave patients with risk factors for poor withdrawal on
current regimens or refer to other services such as old age psychiatrists if appropriate
Complete the Hypnotic data collection form (Appendix 4) (If this is done by PBMC please
pass completed sheet to Prescribing advisor for clinical review)
Standard letter (Appendix 2) sent to patients deemed appropriate to attempt withdrawal,
encouraging them to consider reducing their hypnotic use and set a target of stopping.
Letter explains that they may receive a phone call or be called into surgery for a medication
review. Document in notes that letter has been sent.
Include patient information leaflet ‘Reducing your sleeping (hypnotic) tablets’ (Appendix 1)
along with the patient letter.
Arrange appointment with patient. Practice staff may be able to facilitate this.
GP/Prescribing advisor follows withdrawal programme, provides patient with self-help
guides if appropriate/available, good sleep guide information re-enforced.
Appendix 5 is an aid to use during the withdrawal programme for the Prescribing advisor to
organise clinics and facilitate the withdrawal of hypnotics in patients
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Appendix 1 - Patient Information Leaflet: Reducing Your Sleeping (Hypnotics) Tablets
Sleeping tablets should only be used for short periods of time, used in the long term there can be
unwanted side effects. If used for longer than 2-4 weeks your body can become used to their effects
and the medication may not work as well as it did at first. They should only be used to get back into
normal sleeping pattern.
You may experience the following negative effects from using hypnotics
In the short term:
 Reduced alertness
 Drowsiness
In the long term:
 Dependence on the drug
 Reduced alertness may lead to accidents or falls
 Poorer memory
 Lack of emotion
 Short term effects may continue
Possible withdrawal symptoms that might arise when reducing or stopping:
 Your muscles may ache and you may feel strange sensations on your skin
 You may feel restless and anxious
 You may feel sick and weight loss may occur
 You may have difficulty sleeping
 You may feel frightened or panicky
 Eventually your anxiety will disappear and you will become more assertive
These arise because sleeping tablets block your emotional responses. When the drug is stopped your
brain becomes over stimulated and this can lead to heightening of feelings and senses.
Once stopped
 You should find that you get a better quality of sleep
 You are more alert especially in the mornings
 Your memory improves
 You feel more confident and assertive
Facts about Sleep
 Sleep duration varies from day to day. As people get older they require less sleep
 It is normal for an older person to wake several times in the night. This isn’t harmful. Being
in bed resting can be as good as sleep
 A good night’s sleep may follow a sleepless night, without the need to resort to a sleeping
tablet
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Appendix 2
Prescriber’s Name
Practice Name
Practice Address
Stockport
Patient Name
Patient Address
Date
Dear Mr/Mrs/Ms,
We are currently reviewing all our patients who take the medication…(Insert drug name)…… This
drug is from a group of drugs known as …..(benzodiazepines/ z-drugs) delete as appropriate…..,
which when taken for a prolonged length of time can have negative adverse effects:
•
Dependence on the drug
•
Reduced alertness may lead to accidents or falls
•
Poorer memory
•
Lack of emotion
•
Tasks take longer to complete
•
Poor sleep quality
Importantly, these tablets may actually cause anxiety and sleeplessness and they can be addictive.
For these reasons we would like you to consider reducing your use of your benzodiazepine. Do not
stop taking suddenly as this may cause unwanted side effects, possibly anxiety, restlessness and
problems sleeping. It is recommended to cut down gradually to reduce the likelihood of side effects.
Try cutting down fortnightly when possible, the best way is to use your medication only when
absolutely necessary. Your surgery will be able to advise you on how to reduce. Once you have been
able to cut down, you might start to think about stopping altogether. If you do experience unwanted
side effects reduce at a slower rate such as monthly.
A ‘Good sleep guide’ has been included with this letter. Your local library will also have a selection of
self-help books on improving sleep or combating anxiety and stress. A useful website is:
http://www.rcpsych.ac.uk/mentalhealthinfoforall/problems/sleepproblems/sleepingwell.aspx
If you have any queries regarding this change, please contact the surgery and arrange to speak to
…………………………………. (a named person should be given)
Yours sincerely
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Appendix 3
NHS Stockport ‘Good Sleep Guide’
During
the
Eveningg
At
Bedtime
If you
have a
problem
getting to
sleep
The following tips should help you get into a good sleep pattern
1. Put the day to rest. Tie up loose ends in your mind. A notebook may help.
2. Take some light exercise in the early evening e.g. go for a walk.
3. Wind down in the course of the evening. Try and avoid anything mentally demanding
within 90 minutes of bedtime.
4. Don’t sleep or doze on the sofa.
5. Avoid drinks such as coffee/tea/cola after 6pm. These contain caffeine and can keep
you awake.
6. Make your bedroom comfortable. Not too cold or hot.
1.
2.
3.
4.
5.
6.
Go to bed when you are “sleepy tired”.
Do not watch TV in bed.
Set the alarm for the same time every day until your sleep pattern settles.
Put the lights out when you get in to bed.
Try a relaxing drink such as camomile, horlicks or ovaltine before bed.
Enjoy relaxing even if at first you don’t fall asleep.
1.
2.
3.
4.
5.
6.
7.
Sleep problems are common and not as damaging as you might think.
If you are awake for more than 20 minutes then get up and go into another room.
Do something relaxing and don’t worry about tomorrow.
People usually cope quite well after a restless night. Try reading a magazine or book.
Go back to bed when you are “sleepy tired”.
Remember the tips from the above section.
A good sleep pattern may take a number of weeks to establish. If you have had
problems for years then it will take longer. Be confident that you will get there in the
end!
Appendix 4
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Search Process: Search for the following drugs : Nitrazepam, Flurazepam; Loprazolam; Lormetazepam; Temazepam; Zopiclone (ZIMOVANE); Zolpidem
(STILNOCT) ;Zaleplon (SONATA); Chloral hydrate (WELLDORM); Clomethiazole (HEMINEVRIN)
1. For patients with a PRN dose give an indication of prescription frequency
Patient
Age
Hypnotic Name
PRN
Quantity
Repeat
Name
Dose
Yes
on script
(R) /
And number
Strength
/No
Regular/
Acute (A)
Irregular
Date
started
Initiated
by
e.g. GP,
Hospital
Diagnosis
e.g.
insomnia,
anxiety
Is there
documented
evidence of
withdrawal/
dose
reduction
GP Action:
Leave
Letter
Appointment
PBMC
Action:
Letter sent,
Appointment
date
Appendix 5
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
Patient Name
DOB
ID
Drug
Current dose
Actual Dose taking
Plan
1)Reduce
2) Convert to Diazepam
3) Need clinic apt- Phone/Face to Face
4) Stop
5) Home visit
Appt Date
+ Type
Guidance for Prescribing and Withdrawal of Benzodiazepines and Hypnotics
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
A Protocol for Prescribing and Withdrawing Benzodiazepines. St Helens Primary Care Trust.
Ashton HC. The Ashton Manual. Institute of Neuroscience, Newcastle University. 2002.
British National Formulary (64) London. The Pharmaceutical Press. September 2001.
Benzodiazepines and Newer Hypnotics. MeReC Bulletin 2005; vol 15, No 5:17-20.
http://www.cks.nhs.uk/benzodiazepine_and_z_drug_withdrawal. (Accessed 3.09.12)
Clinical Knowledge Summaries. Benzodiazepine and Z-drug withdrawal. 2012.
Committee on Safety of Medicines. Benzodiazepines, dependence and withdrawal
symptoms. Current Problems 1988;21:1-2.
Gustavsen I, et al. Road traffic accident risk related to prescriptions of the hypnotics
zopiclone, zolpidem, flunitrazepam and nitrazepam. Sleep Med 2008;9:818–22
Kripke D, Langer R, Kline L. Hypnotics' association with mortality or cancer: a matched cohort
study. BMJ Open 2012. Vol 2. Issue 1.
Material to support appropriate prescribing of hypnotics and anxiolytics across Wales. Welsh
Medicines Partnership. April 2005.
Wagner AK, et al. Benzodiazepine use and hip fractures in the elderly. Arch Intern Med
2004;164:1567–72
Zopiclone or zolpidem increase the risk of road traffic accidents. MeReC Monthly No 11. Feb
2009.