Introduction WHY ARE WE STILL STUCK AROUND BENZODIAZEPINES? • Benzodiazepines have always been a problem • “Most loved addiction” • Not much help available • 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 • 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 • • 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 • 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 • • • • 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 • • • • 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 • • 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 • 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 • • Many different people • All ages • Both genders • But about half of population don’t find BZ effects positive or reinforcing • Spectrum of people ranging from therapeutic users to pleasure-seekers • But there is commonality • 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 • • • For both, start with addressing underlying problems • 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 • Practical prescribing • Three common starting points for discussions with patients: 1. 2. • 3. • 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 • • 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 • • • • • • Long-term use: memory impairment and cognitive effects • • • • • • • 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 • • • • • 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 • • • • • 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 • • • • • • • • • • Anxiety Dysphoria Muscle pains Tremor/shaking Fatigue Visual & sleep disturbance Headache Sweating Nausea/anorexia Weight loss Symptoms of BZ Withdrawal Syndrome Major incidents • from recurrence of anxiety: • • • • • • • 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 • 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) • • 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 • 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 • • 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 • • • • • • 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: • • • • • • • • • 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 7. • 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: 6. No substitute drugs for BZ, so generally best avoided Rarely, indications for: Reassure / sleep hygiene / melatonin (short) (??zopiclone) Difficulty coping with BZ withdrawal symptoms 5. • Increase psychosocial support Difficulty sleeping: 4. • Treat psychiatric problems more effectively Difficulty coping with stress: 3. 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 • • Longer term prescribing? • 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 • 1. Therapeutic-dose BZ users • • • • • • • • • • • • • • • 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 • • • • • 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 • • • • • • • • • • • • • • • 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 • 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 • • 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 • BZs in people who use illicit drugs / are in drug dependence treatment • • • • • • • 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 • Potential harms associated with BZ use among drug users • Use of BZs amongst heroin users and those on OST appears • • • • • 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 • 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 • • • 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 • Key messages • • • • • • • 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 • • 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 • • • • • 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? 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