Download WHY ARE WE STILL STUCK AROUND BENZODIAZEPINES? Introduction SMMGP Manchester, October 2013

Introduction
WHY ARE WE STILL STUCK
AROUND BENZODIAZEPINES?
• Benzodiazepines have always been a problem
• “Most loved addiction”
• Not much help available
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I am personally in recovery from benzodiazepine workshop
dependence…
• Second most commonly prescribed drug
SMMGP Manchester, October 2013
• Unsure what to do
• Wide divergence between published guidelines and clinical practice
Dr Martyn Hull
Lead GPSI, Birmingham
Medical Director, Swanswell
Clinical Lead, RCGP Certificate in Drug Misuse
• Wide variety in clinical practice
• BZ sometimes given as “quick fix” in general practice
• Sometimes BZ given rather than opioid
• Guidance not realistic?
Background
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BZs are widely prescribed
• Short-term for a variety of conditions
• Efficacy well established (anxiolytic, hypnotic)
Combination of effectiveness and risks of long-term use
• Often a wide divergence between guidelines and clinical
practice
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• Guidelines suggest maximum prescribing of 2-4 weeks
• In practice this is often not the case
• This also does not help patients who are already on long-term
prescriptions, or their prescribers
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History of benzodiazepines
• Introduced 1960s – advantages over available hypnotics: barbiturates
• 1959 – chlordiazepoxide was first BZ to be marketed for insomnia and
anxiety
• In 10 years, had >90% share of market previously dominated by
barbiturates
• Compared to barbiturates, initially appeared to have improved safety
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profile, safe in OD, greater anxiety reduction & no physical
dependence potential
This last claim was soon found to be untrue
Though safer than barbiturates, soon emerged that tolerance,
dependence and withdrawal symptoms were common in those taking
BZs long-term
During 1970s and 1980s prescribing increased dramatically
Over last decade, prescribing has remained stable but that of BZs
used for anxiety has steadily risen
This is the reason why BZs cause us such a headache
Prevalence of use
• 2007 report: 0.5% of population reported tranquilliser use in last year
• Highest in North East (0.8%) and Wales (1%)
• Lowest in East Midlands (0.2%), North West (0.3%) & East of England (0.3%)
• In 1988, CSM recommended limiting length of
• Non-white population much less likely to have used
• This was reiterated by CMO in 2004, based on DH
• Number of people taking prescribed BZs worldwide is enormous
• In USA 2% of adults (4 million) have been prescribed for 5–10 years or more
• Number of people dependent on BZs in UK is unknown (never been
calculated) but may be between 0.5 and 1.0 million people
• In 2004, study undertaken in 7 GP practices found long-term (6
months or longer) BZ users = approx. 185 pts / practice
treatment to 2-4 weeks
data which showed
• 30% of prescriptions written by GPs were for 56 or more
tablets
• 56% were for people over 65 years of age
• Over the last decade the level of combined BZ and Z-
• Females out numbering men by a ratio of 2:1
drug prescribing has remained stable but:
• Most prescribed by doctors for ‘therapeutic’ use
• Men are more likely than women to have used illicit tranquillisers
BZ and Z-Drug hypnotics in the community
(e-PACT data)
• Increase in BZ (particularly diazepam) for anxiety
• Increase in Z-drugs (replacing BZ) for sleep disturbances
Current prescribing - we are still doing
it!
12
All BZ & Zdrug
hypnotics
Millions of Prescriptions
10
8
BZ hypnotics
6
4
Z-drug
hypnotics
2
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Properties and clinical actions
• BZs have six main clinically relevant actions:
• Anxiolytic
• Hypnotic
• Anticonvulsant
• Muscle relaxant
• Anterograde and retrograde amnesia
• Alcohol withdrawal
• Pharmacokinetics vary widely (what body does to drug e.g. how long the
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effects last)
Pharmacodynamics similar (what drug does to body)
Potency varies greatly
Can be classified according to main use, speed of onset, duration of
action and drug half-life
This gives an indication of when withdrawal symptoms are likely to begin
Speed of onset and peak effects
• BZs rapidly and fully absorbed orally; peak effects within half-
hour to two hours of ingestion
• More fat-soluble drugs (e.g. diazepam) absorbed faster & enter
CNS more rapidly than less fat-soluble drugs (e.g. oxazepam)
• Hence more fat-soluble agents have increased abuse potential
• BZ with long half-lives - diazepam and nitrazepam - more likely
to produce residual effects such as sedation and falls next day
• Rapid-onset drugs associated with ‘good’ subjective effects
(cause greater intoxication), result in psychological
reinforcement every time taken
• Over time, this strengthens psychological component of any
dependence process – this is key factor for risk of abuse
• Second most important factor related to risk of abuse is dose,
as higher dose leads to a better ‘buzz’
Duration of action and metabolism
• Duration of clinical action considerably shorter than their elimination
half-life because once absorbed, rapidly redistributed into fatty tissue
Rapid Onset
Intermediate
onset
Slow onset
Flunitrazepam
Temazapem
(caps or solution)
Lormetazepam
Lorazepam
Temazepam
(tablets)
Oxazepam
Loprazolam
Diazepam
Nitrazepam
Flurazepam
Alprazolam
Chlordiazepoxide
Clonazepam
Clobazam
• With repeated daily dosing, accumulation occurs; high concentrations
can build up in body
• With repeated dosing, steady state reached in about 5 half-lives
• After prolonged use, urine tests may remain positive for 6 weeks after
cessation, as drug slowly leaches out of fatty tissues
Ultra short half life Midazolam
Zopiclone
(< 8 hours)
Zolpidem
Zaleplon
• Although noticeable clinical effects usually wear off within a few
Short half life
(8 - 24 hours)
Long half life
(over 24 hours)
hours, most BZs continue to exert subtle effects within body, which
may become apparent during continued use
• Diazepam, for example, typically given 2-4 times daily for anxiety,
despite its elimination half-life being two days and its active
metabolite having an elimination half-life of four days
• BZs differ in the speed at which they are metabolised
Anxiolytic
Mechanism of action
Hypnotic
Anxiolytic/hypnotic
Anticonvulsant
Benzodiazepine effect at GABA receptors
Actions of BZs mediated by enhancing the activity of GABA, an inhibitory
neurotransmitter that transmits messages from one neuron to another
• BZs bind to receptors on GABA-A receptor complex: can directly or indirectly
affect almost every part of brain function unselectively
• This “inhibitory” effect is responsible for characteristic effects of sedation,
amnesia and motor incoordination
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• Affect mesolimbic dopamine system, which damps down emotions inc. fear, anxiety,
pleasure (from reward systems) leads to ‘emotional anaesthesia’, apathy & depression
• In cerebral cortex they cause cognitive impairment and drowsiness
• In hippocampus they cause memory impairment
• In cerebellum, they have have anticonvulsant actions
• In motor areas, interfere with balance, motor control, muscle tone and coordination
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These effects become more marked in with increasing age & in long-term use
Tolerance
Who uses benzodiazepines?
Tolerance (neuroadaptation) is a physiological reaction:
original dose of drug has progressively less effect and
higher dose is required to obtain original effect
• In case of BZs, compensatory changes occur in the GABA
and BZ receptors, which become less responsive, so that
inhibitory actions are decreased
• Rate of development of tolerance may be rapid, but varies
for different drug effects; relief of anxiety, sedation and
pleasure (depending on no. / complexity of receptors)
• Can also develop at different speeds, which vary between
individuals and can change in individuals over time
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Many different people
• All ages
• Both genders
• But about half of population don’t find
BZ effects positive or reinforcing
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Spectrum of people ranging from therapeutic users to
pleasure-seekers
• But there is commonality
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Most frequently prescribed for insomnia and anxiety
• These are areas we will initially concentrate on
Treatment of insomnia and anxiety
Pharmacological treatment
Insomnia is an important, common - usually long-term health problem that requires accurate diagnosis and
effective treatment
• Anxiety symptoms may range from mild and transient
without daytime functional impairment, to severe and
persistent causing significant distress
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For both, start with addressing underlying problems
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Then use: talking therapies, CBT & self-help
Pharmacological treatment – other
options
• The “Z” drugs - zopiclone, zolpidem and zaleplon - were developed
as hypnotics to overcome side effects associated with BZs, though
their potential to cause tolerance, dependence and withdrawal
symptoms was known from the beginning
• Have been shown to be effective hypnotic treatments for insomnia in adults & are
comparable to BZs in hypnotic efficacy
Though biochemically distinct from BZs, Z-drugs have similar pharmacological action
• May have clinical indication in elderly (shorter half-life therefore less “hangover”
effect) and when perceived risk of abuse
Drug treatment is not first line - can include:
• Benzodiazepines, Z-drugs, SSRIs, melatonin
Drug treatment may be indicated in specific situations
such as acute crisis with a clear endpoint or a predicted
acute crisis
• If considering BZs, should be used in lowest possible
dose and for shortest possible time (max 2-4wks)
• Not indicated for long-term treatment of anxiety or
insomnia or to treat short-term mild anxiety
• BZs primarily relieve and suppress symptoms, rather than
being curative for any disorder
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Practical prescribing
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Three common starting points for discussions with patients:
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• Melatonin is an endogenous hormone produced by the body in
response to darkness that helps regulate circadian rhythms
• Can be used for insomnia in adults aged 55 and over for up to 13
weeks (2mg M/R nocte)
Practical prescribing
• Prescribing for first two indications is least contentious, but even so, one
should explore other options first
• If decide to prescribe BZs, should be a short-term measure only
• Caution must be used when prescribing to anyone, but more so when
current / past history of substance misuse or personality disorder
• Having once started it is harder to stop
• Discuss at outset of treatment the need for short course only
• Explain possible side effects (driving etc.), adverse effects and drug
interactions (e.g. alcohol) plus risks of long-term use
• Plan reduction from outset, and show how to manage rebound effects
• Generally use diazepam for anxiety; avoid potent short-acting BZs such
as lorazepam
• For insomnia, shorter-acting drugs (e.g. Z-drugs & temazepam) should
be used in preference to longer acting drugs (e.g. nitrazepam) as they
cause less ‘hangover’ effects
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Patient has acute self-limiting anxiety or insomnia, other
treatments such as counselling and medication have failed and
immediate relief is requested
Patient has acute self-limiting anxiety or insomnia, has used BZs
or other drug before to good effect and requests them again
Patient has used BZs over a long period, has a dependence on
them, may or may not be dependent on other drugs and / or
alcohol too, and requests help
These are very different discussions that share some common
ground
Each should be addressed appropriately
Established benzodiazepine
dependence
Prescribing for patients with established benzodiazepine
dependence, is more controversial
• But not addressing it and / or abrupt withdrawal of BZs
carries significant risks
• Where non-prescribed BZs are involved, the situation is
more complex still
• Many individuals taking illicit BZs operate in the context of
poly-drug use, including alcohol
Problems with long-term use
BZ & related drugs are usually effective when first
prescribed
• Nearly all disadvantages & problems come from longterm use
• The longer they’re prescribed, the more likely patients are
to get adverse effects
• Long-term use of BZs are associated with considerable
physical, mental and social health problems
Long-term use: increased anxiety
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Long-term use: memory impairment
and cognitive effects
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BZs have long been known to cause amnesia:
• Desirable effect when they are used as pre-medication for surgery
• Undesirable when the drugs are taken on a regular basis
Memory impairment occurs because BZs cause a lack of concentration and
also provoke a specific deficit in new memory formation
May lead to memory lapses or ‘blackouts’, when patients may do something
under the influence of BZs they don’t recall (transient global amnesia)
Chronic effects on memory are likely to result in reduced social functioning
over time, e.g. reduced ability to remember new people or plans
The question of whether long-term BZ use results in brain damage has never
been adequately studied and remains controversial
Long-term use of BZs has been associated with long-term cognitive effects
Moderate to large deficits occur in long-term BZ users and may mimic
dementia in the elderly
Anxiety can be caused by BZs themselves, as well as
associated with reduction / cessation
Anxiety reduced if BZs are stopped in 40–60% of
patients
After several years on BZs, patients may experience a
gradual increase in anxiety, panic attacks and
agoraphobia
The increase in anxiety should not be treated with
additional BZ
Patients may also develop a preoccupation with BZs and
the dose they are taking (‘benzodiazepine neurosis’),
which makes it difficult to implement appropriate changes.
This typically resolves only once the drug is stopped
Long-term use: depression, emotional
blunting and reduced coping
• Emotional blunting is a common complaint of BZ users
• Inhibition of arousal results in an inability to feel normal emotional
highs or lows, pleasure or sadness, and grief
• Long-term BZ users sometimes develop depression (which typically
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resolves within 6 months or a year of stopping BZ)
BZs may also aggravate existing depression - possibly by reducing
brain's output of neurotransmitters
Sometimes BZs precipitate suicidal tendencies in depressed patients
Long-term use of BZs also typically results in weakening of coping skills
• Patients use them in their repertoire of coping mechanisms
An increased intensity of emotions may occur on reduction and continues
even after rebound and withdrawal symptoms have resolved
Traumatic issues, such as abuse and other difficulties, may be
reactivated, and result in the emergence of PTSD
• These issues usually settle within 6–12 months of stopping BZs
Long-term use: disinhibition /
paradoxical stimulation
Dependence and withdrawal symptoms
• BZs occasionally cause paradoxical excitement with increased
• The dependence syndrome occurs when the user of a substance
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anxiety, insomnia, nightmares, hallucinations, irritability, hyperactivity
or aggressive behaviour, and exacerbation of seizures in epileptics
Such reactions are similar to those sometimes provoked by alcohol
They most frequently occur in anxious and aggressive individuals,
children and the elderly, and following high doses of BZs
Probably due to release of inhibited behavioural tendencies that are
normally suppressed by self-control and social restraints
Suicidality and self-harm may also occur
Cases of non-accidental injuries in children and the elderly, as well as
incidents of domestic violence, have also been attributed to BZs
• High-dose BZ-users may also feel euphoric and disinhibited & engage
in disinhibited or uncharacteristic behaviour - “Rambo syndrome”
becomes less able to control its’ intake
• Dependence to BZs comprises:
• Compulsion/cravings to take BZs
• Difficulties in controlling BZ use
• Progressive neglect of alternative pleasures / interests due to BZ use
• Persistent BZ use despite harmful consequences
• Characteristic BZ withdrawal state
• Evidence of tolerance to BZs
• Characteristic withdrawal syndrome
• Long-term use causes withdrawal symptoms in many
• Withdrawal symptoms fall into 3 groups:
• anxiety symptoms
• distorted perceptions
• major incidents
Symptoms of BZ Withdrawal Syndrome
Anxiety symptoms:
Symptoms of BZ Withdrawal Syndrome
Distorted perceptions
•Can mimic symptoms BZ was first taken for and also appear on rebound
• May be useful as new symptoms to help distinguish withdrawal
as BZ stopped
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Anxiety
Dysphoria
Muscle pains
Tremor/shaking
Fatigue
Visual & sleep disturbance
Headache
Sweating
Nausea/anorexia
Weight loss
Symptoms of BZ Withdrawal Syndrome
Major incidents
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from recurrence of anxiety:
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Hypersensitivity to stimuli (sound, light, touch, taste, smell)
Abnormal body sensations (distortion of body image, formication, muscle
twitching or fasciculations, tinnitus, burning sensations)
Abnormal sensation of movement (floor undulating, walls tilting)
Depersonalisation
Derealisation
Paraesthesia
Extreme dysphoria
Likelihood of more severe withdrawal
syndrome
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Pharmacological:
• Longer term use (> 4 months)
• Higher than therapeutic dose use
• Higher potency, short half-life BZ (e.g. lorazepam, alprazolam)
Occur especially if high doses are stopped abruptly:
• Epileptiform seizures (1-2% of high doses stopped abruptly)
• Visual hallucinations (rare)
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• Delirium (rare)
Related to chronic problems:
• Chronic psychiatric & personality problems
• Chronic physical health problems: esp. elderly, or in those with
• Psychosis (very rare)
chronic sleep problems
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Increased physiological risk of dependence:
• Current / past alcohol or other sedative-hypnotic dependence (or
possibly even a FH of this)
Protracted withdrawal syndrome
Success of reduction
Occurs in up to 15% of patients
Most have taken BZs for many years – over 20 years
• Most symptoms go within 1 year
• Reduction and cessation of BZs in long-term
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users is possible in most patients who are
dependent if done slowly and with psychological
support
• But need to address problems related to prolonged use
• Long-term cognitive effects disappear in most people 6-12 months
after stopping
• Relapse after successful detoxification is lower
with BZs than other drugs
Detoxification for BZ dependence
The detoxification
• Consideration of when and how to detoxify
• Are they emotionally ready?
• Do they understand the advantages of stopping?
• Extra help and services needed
• Remember to ask about alcohol
• It is easy to substitute alcohol for BZ
• Before starting a reduction:
• Tackle any underlying problems causing anxiety or insomnia
• Ensure any physical or psychiatric health problems are treated
• Tailor and taper the dose reduction to the individual
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• Continuing symptoms are strongest predictor of failure
Give information about the problems of long-term BZ use
Explain the process of withdrawal and possible effects
Sleep hygiene
Ensure stress or grief are being addressed
Work on coping strategies
• Reduce dose sequentially & maintain dose with each reduction
until withdrawal symptoms improve
• Split dose to three times a day
• Monitor frequently
• Assess the need for additional psychosocial support
• Enquire about progress / withdrawal & rebound symptoms
• If experience difficulties with a dose reduction, encourage to
persevere
• Suggest delaying the next step down
• But try not to revert to a higher dosage
• Consider substituting short / medium acting BZ with long-acting
BZ (e.g. diazepam)
Dealing with BZ detoxification
problems
1. Rebound anxiety / insomnia:
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be used if depression present or emerges during withdrawal – if so,
sedating antidepressant may be best – e.g. mirtazipine – BUT care
needed as may initially worsen anxiety, and less effective if
concurrent alcohol or stimulant use
• Beta-blockers – short term management of physical sx of anxiety
(palpitations, panic, tremor)
• Antiepileptics / Mood stabilizers – e.g. carbamezepine – may
reduce withdrawals, particularly risk of seizures (may be used
instead of BZ for withdrawals from high-dose BZ, usually in-patient)
• Melatonin – may facilitate BZ detoxification
• Flumazenil – BZ antagonist – need more evidence
Use slow onset, e.g. oxazepam
Using different amounts each day or binging
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• Antidepressants – no indication to help BZ withdrawals, but may
Use longer half-life e.g. diazepam
Reduce rate of reduction or hold dose until sx subside
Increase psychosocial support
Liking BZ too much to reduce it:
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No substitute drugs for BZ, so generally best avoided
Rarely, indications for:
Reassure / sleep hygiene / melatonin (short) (??zopiclone)
Difficulty coping with BZ withdrawal symptoms
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Increase psychosocial support
Difficulty sleeping:
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Treat psychiatric problems more effectively
Difficulty coping with stress:
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Other pharmacological treatments
Reassure (and prepare at start of treatment)
Continuing anxiety / depression:
2.
Increase frequency of pickup, DPU (diazepam) - ?supervision by
relative / pharmacist
Longer term prescribing?
RCPsych: ‘the decision to allow dependence to develop is sometimes
defensible but… once dependence established, often extremely difficult to
treat and may become a long-term or even permanent state’
• Decision to prescribe longer-term should be rare and made with care; may be
considered when:
1. In treatment of resistant, persistent and severe psychiatric illness
2. In BZ users, where there are withdrawal symptoms that are persistent,
debilitating or intolerable, or in long-term users who are unable to stop
3. As part of a harm reduction treatment, in those who have an inability to stay
off alcohol or illicit BZs but in whom the harm reduces significantly when on a
BZ prescription
• In this case continuing to prescribe (e.g. diazepam) may cause less harm
than stopping the prescription, especially if the patient is HCV positive
• The BZ script should, however, be stopped immediately if the patient
relapses to alcohol or illicit BZs
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Longer term prescribing?
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Such prescribing must meet the following criteria:
Treatment must be for a recognised illness or disorder,
with which alternative treatments with non-addictive drugs
have failed, i.e. treatment resistance exists
• The benefits of treatment must outweigh the risks
• The decision is taken in conjunction with patient, who
must accept increased risks, such as memory problems,
emotional suppression and dependency syndrome etc.
• The treatment is individualised and reviewed periodically
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1. Therapeutic-dose BZ users
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Female > Male; age >40 yrs
Never or rarely use other drugs
Seek relief from unpleasant (negative) symptoms, e.g. insomnia, anxiety
Low doses are sufficient, over an extended period of time
Continuing efficacy reported, so happy on current dose
May seek hypnotic effects to which tolerance may develop; or anxiolytic
effects, with less development of tolerance – dose escalation uncommon
If escalation occurs, it is to treat the problem more effectively (rather than for
pleasure), so illicit use is rare
Stable daily dose which is constant or decreasing over time
On a legal script or self-medicators who do not typically abuse BZ
For anxiety typically take BZ 3–4 times a day for maximal effect
For insomnia, typically taken once daily at night time for night sedation
Easier to treat, especially in primary care
Low control / monitoring over treatment required
Engage well in treatment
Relapse risk low following cessation
3. BZs in mental illness
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BZs used much less in mental illness than used to be but
still prescribed extensively, partic. after acute admission
Proven efficacy, e.g. treatment of GAD & social phobia
Because of risks of sedation and dependency, are now
3rd line treatments after SSRIs & psychological treatment
Remain useful in small number of patients
Dose escalation does not usually occur and concerns
about potential problems in long-term use should not
prevent their use in patients with persistent, severe,
distressing and impairing anxiety symptoms
Different groups who are BZ
dependent
1. Therapeutic dose users
• Sometimes called ‘involuntary addicts’
• Started for a specific reason and continued
2. High dose users
• May have started prescribed then escalated dose, often
with illicit BZs
• May use other illicit drugs, OTC / POM + / - alcohol
3. Those with a psychiatric problem
• Overlap between all these groups
• Important to distinguish as approach will differ
2. High-dose BZ users
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Male > Female; Age <30 yrs
Often use other illicit drugs (⅔ use opiates) regularly or in binges
Seek positive effects that give fun or pleasure / high
Seek mind numbing effects, sedation, euphoria or memory suppression
Lower doses not sufficient as tolerance soon develops to these effects
Often binge, use with other drugs to potentiate the effects
Prefer rapid onset / potent BZ
Use techniques to increase the speed of onset of effects
Often obtain BZ illicitly from other users or via internet
May supplement prescribed dose or “doctor shop”
Typically take BZ as single dose in day to maximize euphoria, often
with other sedative drugs (e.g. opiates) to enhance the ‘buzz’
More difficult to treat; may need specialist
High control / monitoring needed
Typically difficult to engage in treatment
Relapse risk high following cessation
BZs in people who use alcohol
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BZs (chlordiazepoxide, diazepam) have proven value in alcohol detoxification
Role of BZ outside of this is less clear
Appears to be widespread use of BZs in primary care for patients wishing to
reduce alcohol, and for those who have stopped drinking – effectively
substituting BZ dependence for alcohol dependence
• No evidence to support this approach
• Combination of BZs and alcohol enhances ‘buzz’ experienced, but also
increases the risk of CNS and respiratory depression
• Chronic (though not acute) consumption of alcohol results in enhanced BZ
metabolism, reducing length of action of its effects
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Prescribing BZs to people dependent on alcohol before referring for a
community detoxification is unhelpful and should be avoided, as should
prescribing ‘a small dose of diazepam’ to help alcohol-dependent patients
who claim to ‘have stopped’ or ‘cut down’
• BZs can increase relapse rate and alcohol consumption and increase
cravings in people who have been previously dependent
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BZs in people who use illicit drugs / are
in drug dependence treatment
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BZ misuse a serious problem in people who use drugs,
especially for polydrug users
As well as taken orally, they can be snorted & / or injected
Up to 90% of drug users report using BZs
They tend to increase activity in the brain reward centres
They are also used to alleviate withdrawal symptoms from
other drugs, especially heroin
They are more likely to be taken in binges
May also use be used in this group as self-medication to
improve their mood or their coping skills
Potential indications for prescribing BZs
in patients who use drugs:
Short-term:
•Detoxification from alcohol or other hypnotic withdrawal (but not for
relapse prevention)
•Intractable BZ withdrawal symptoms on reduction programme when all
else has been tried
•Adjunct to detoxification from high use cannabis if marked irritability
•Detoxification from solvents and other alcohol-like substances, GHB,
GBL etc.
•Opioid withdrawal, particularly final stages
•Ketamine withdrawal to reduce anxiety or distress
•Treatment of choice in cocaine-induced delirium, where neuroleptics
may react with cocaine to produce dyskinesia or hyperthermia.
Longer-term
•To terminate illicit BZ use or contact with illicit drug markets
•Chronic hepatitis C and is able to use BZ to stop drinking
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Potential harms associated with BZ use
among drug users
• Use of BZs amongst heroin users and those on OST appears
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Prescribing BZs for BZ dependency
If considering prescribing BZs to illicit users, important to undertake
assessment:
• Amount and pattern of use
• Other drug use
• Withdrawal symptoms including fits
• Physical and psychiatric history
• Also need to assess for BZ dependence:
• At least 2 consecutive recent urine screens are positive for BZs
• No negative urine screens for BZs in the last 4 months
• Evidence from history and symptoms that the patient is physically
dependent on BZs
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In addition, ensure that the benefits of potential treatment will outweigh risks
(diversion, overdose, etc.)
Some evidence that BZ prescribing has little impact on illicit BZ use – may
lead to increased overall use
Reinforces need for reluctance to prescribe, and to do so only in carefully
selected situations
Only anecdotal evidence for this & BZs need to stop if drinking continues
Prescribing BZs for BZ dependency
• All BZs should be converted to diazepam:
• Diazepam has long half-life: allows a smooth and gradual withdrawal
• Different strengths allow flexibility when planning dose reductions
• Diazepam can be issued on an FP10MDA interval prescription
• Only if there are definite problems caused by the rapid onset of
diazepam (e.g. BZ-seeking behaviour, difficulty reducing) should an
alternative slow-onset BZ such as oxazepam be used
Prescribing for those who use opiates & BZs
Treat the opioid dependence first – with OST
Discuss with patients how they will control and reduce
BZs - many are able to reduce their illicit use
• Reassess patients’ BZ use once stable on OST
• If use of BZs is continuing, reassess the reasons
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• For sedation, ‘buzz’, anxiety, comedown from crack / other drugs?
• Does it enhance the opioid ‘buzz’?
• Rarely need >30 mg daily - lower starting dose may be adequate
• 30 mg sufficient to protect against fits, even in patients taking more
• Encourage patients with poor sleep to split dose and keep 1/3 for night
• Aim for structured detoxification – clear explanations / care plan, role
for boundary-setting (stick to these!), frequent review – ensure that this
does not lead to de facto maintenance prescribing
to lead to higher rates of risk-taking behaviour and social
dysfunction, and can contribute to fatal overdose
HIV and other infections are more common in people using
opioids plus non-prescribed BZs: little evidence that these risks
reduce if the drugs are prescribed
Use of opioids in combination with BZs is associated with
increased opioid toxicity
Dependence and tolerance are significant problems with these
drugs and probably worse in dependent populations.
Withdrawal symptoms are worse with longer use
There is a risk of diversion on to the illicit market
• Do not prescribe BZs if use is for pleasure or in binges
If BZ dependence present, consider structured reduction
as with other BZ-dependent patients
• Stop the BZ prescription if persistent illicit BZ use or
alcohol dependence
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Key messages
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BZ not 1st line treatment for insomnia & anxiety
BZ suppress symptoms only, and risk dependence
If use, short-term only; better still not to start in first place
Multiple long-term adverse effects
If been on BZs long-term: explain, support and aim for
detoxification; use individualised plan, don’t hurry
Success of detoxification good, and low risk of relapse
Longer-term use only if risks are understood & stopping
would be worse than continuing
Guidelines
• Guidance for the use and reduction of misuse of benzodiazepines
prescribing and other hypnotics and anxiolytics in general practice
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• Chris Ford & Fergus Law, SMMGP (Draft 2013)
BAP (British Association for Psychopharmacology, www.bap.org.uk) which have
provided guidance on:
• a) Anxiety (2005), Evidence-based guidelines for the pharmacological treatment of anxiety
disorders: recommendations from the British Association for Psychopharmacology
• b) Insomnia (2010), British Association for Psychopharmacology consensus statement on
evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders
• c) Substance misuse (2012) Evidence-based guidelines for the pharmacological management of
substance abuse, harmful use, addiction and comorbidity
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NICE on Insomnia (2004), anxiety (2005, 2011)
CKS NICE on Benzodiazepine and z-drug withdrawal (2009)
DH Orange Guidelines (2007)
Royal College of Psychiatrists (1997)
Educational pack to support the appropriate prescribing of hypnotics and
anxiolytics across Wales (2011)
Questions?
[email protected]
[email protected]