Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Sedative quality of methadone
- Jonathan C Haynes, Sam Forshall, Consultant in Addiction Psychiatry (9 December 2005)
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Buprenorphine in opiate addiction
- Graham Brack (9 December 2005)
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Methadone deaths. What about Heroin, Alcohol, Benzodiazepines etc?
- Roger L Weeks (12 December 2005)
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Medical change has always needed overwhelming evidence
- Andrew J Ashworth (14 December 2005)
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There is not a case to replace methadone by buprenorphine
- Chris H Ford (15 December 2005)
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Toxicity versus Acceptability
- Adam Bakker, Vanessa Sibanda (15 December 2005)
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Safer alternatives to methadone overdue
- Clive L Morrison (15 December 2005)
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Re: Methadone deaths. What about Heroin, Alcohol, Benzodiazepines etc?
- David O Yates (15 December 2005)
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Methadone still needed in addiction treatments.
- Andrew Byrne, Richard Hallinan (15 December 2005)
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partial agonist effect of buprenorphine
- ivor p hodgson (15 December 2005)
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lack of evidence
- Jim L Barnard (16 December 2005)
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response to editorial
- george ryan (16 December 2005)
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Choice versus Hobson's Choice
- Gordon R. Morse (16 December 2005)
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Get the facts right please
- Adam Bakker (18 December 2005)
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shooting ourselves in the foot?
- stephen brinksman (19 December 2005)
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Buprenorphine is no wonder drug remember temegesic.
- Jeff Fernandez (19 December 2005)
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Better drug treatment infrastructure needed
- Michael P Scully, Eamon Keenan, Consultant Psychiatrist and Clinical Director (19 December 2005)
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Patient choice cannot be ignored/crushing buprenorphine prevents diversion
- Susi R Harris (20 December 2005)
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Re: Get the facts right please
- Clive L Morrison (21 December 2005)
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Deaths involving methadone and buprenorphine were underreported while the risk of methadone poisoning was overestimated
- Oliver WC Morgan, Clare Griffiths and Matthew Hickman (22 December 2005)
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Response to the editorial "Is methadone too dangerous for opiate addiction?"
- Marina Davoli, Laura Amato, Simona Vecchi, Pier Paolo Pani, Carlo A Perucci (30 December 2005)
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Buprenorphine: no evidence of benefit at three times the cost
- John Robson (1 January 2006)
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Buprenorphine is safer than methadone for antenatal opioid addiction.
- Swapna Patankar, A.J.S. Watson, D.Cardell, G.Martin, I.Telfer (4 January 2006)
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The relative safety and efficacy of methadone and buprenorphine
- Billy Boland, Fabrizio Schifano - Senior Lecturer in Addictive Behaviour, Colin Drummond - Professor in Addiction Psychiatry. (13 January 2006)
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Flaws in the argument 'Is methadone too dangerous for opiate addiction?'
- Linda D Harris, Chris Ford, Mark B Gabbay, Jenny Keen (17 January 2006)
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Re: Methadone deaths. What about Heroin, Alcohol, Benzodiazepines etc?
- Kristan E Hilchey (19 January 2006)
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Jonathan C Haynes, Specialist Registrar, Addiction Psychiatry North Somerset Specialist Drug & Alcohol Service, Sam Forshall, Consultant in Addiction Psychiatry
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The authors present many of the issues to be taken into consideration when deciding whether to commence an opiate dependent patient on buprenorphine or methadone. However, they have failed to mention the different sedative qualities of the two medications. It is our experience that very many opiate dependent patients suffer considerable emotional distress and use heroin as a form of self- medication. The use of buprenorphine in this patient group is successful in the relief of withdrawal symptoms, but its relative lack of sedative properties unmasks emotional distress and is a barrier to stabilisation and discontinuation of on-top heroin use. It is therefore our practise to commence patients on methadone, with supervised consumption, and to encourage participation in appropriate counselling. Once stable, methadone is reduced, and frequently patients are converted to buprenorphine to complete the detoxification process, at a stage when issues predisposing to emotional distress and drug use have begun to be addressed. Competing interests: None declared |
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Graham Brack, Community pharmacist Truro TR1 3DN
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The editorial by Dr Luty and colleagues (10 December, pp 1352-3) contains much of interest. As a community pharmacist, I have been supervising methadone consumption for nine years, and over half of our patients continue to consume on the premises. Part of the reluctance of pharmacists to supervise consumption is, of course, linked to the lack of any national funding. The fee we received in 1996-7 is still the fee we receive today. One might expect that the added time required for supervision of consumption would be paid for. This is, however, even more true of supervision of buprenorphine. Whereas we can supervise a methadone client within a couple of minutes once they know our routine, this is not possible with buprenorphine. The clients must sit for a few minutes until the tablet is throughly softened - experience has shown that even half-sucked tablets have a market value. While they are sitting, the pharmacist must watch them, which precludes his doing anything else, and denies the client the anonymity that a quick drink from an opaque cup offers. This is not to say that these difficulties are insuperable, but they need to be considered by those designing and commissioning services, and a higher supervision fee for buprenorphine - reflecting the longer time needed - is to be expected. Competing interests: None declared |
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Roger L Weeks, GP Deanhill Surgery SW14 7DF
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I might well agree with Luty et al that buprenorphine is a better drug than Methadone for heroin replacement in addiction but it is misleading of them to cite the three bugbears of Methadone deaths, failure to ensure supervised consumption and diversion of Methadone to the black market to back their case. 1. Firstly annual Methadone deaths have been falling since a peak in 1997, the actual numbers as quoted by Luty are in fact very small (a) given the number of prescriptions issued and (b) given that these prescriptions are given to addicts many of whom suffer co-morbid mental illness including depression. The fact that a few addicts chose Methadone (usually with other drugs) to kill themselves and others misuse Methadone and die is not evidence for changing from Methadone to Buprenorhine. The numbers of Buprenorphine deaths are much much lower but then so are prescriptions. 2. Secondly supervised consumption is only appropriate, in my view, in the titration of Methadone dose and is not useful, indeed, counter-productive long term. How do we expect out of control drug addicts to control their drug consumption if we cannot trust them to take their medication alone? Apart from further depressing the addict's rock-bottom self esteem this practice has no effect on addict behaviour. 3. Thirdly diversion of Methadone or any drugs to the black market is a problem but is it a serious problem and does it really matter? Why should we always be thinking of ways to reduce diversion when struggling with much more devilishly difficult issues with our addicts? Should our prescribing and administration of medications actually be governed by considerations of diversion. If so does this actually help our patients? In the present climate of blame if I prescribe Methadone to my patient and it ends up with someone else and they take it and die in some people's eyes I am at fault. Can I beg for mercy for all the addict life years I have saved by prescribing Methadone? Our inadequate drug addiction services are plagued by rules which have nothing to do with treating drug addiction and everything to do with the predjudices and moralistic views of our society about drug addicts. Drug addicts feel they are the dregs of society and our services confim that this view is shared by society. Services to drug addicts should be designed to take patients out of drug use, out of crime, provide appropriate, titrated relacement where needed, deal with their many medical and social needs and retain them in treatment for as long as necessary. In addition therapy should be directed to raising the addict's self esteem by trusting them to control their actual drug consumption and thus grapple with their addictive behaviour. Competing interests: Roger Weeks is a GP in a PMS + practice providing poly-drug addiction services to more than 90 addicts in London. |
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Andrew J Ashworth, GP Principal Davidson's Mains Medical Centre, Edinburgh, EH4 5BP
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Though Buprenorphine is safer than Methadone as well as being at least as effective, the ignorance of its characteristics by our profession are simply a symptom of our resistance to alter established practice until the evidence becomes so overwhelming that we must change. Since Lister was pilloried for suggesting that obstetricians wash their hands, medical traditionalists have held greater sway than medical innovators.We feel more comfortable with a more dangerous drug we know well than an unfamiliar, albeit safer, alternative. As well as having lower mortality, Buprenorphine is more flexible because of its opiate kappa blocking properties (which lead to some of its less sedating qualities through improved dopamine release in the Nucleus Accumbens) and is potentially more effective as a treatment agent (blocking the effects of dynorphin, the endogenous kappa agonist that may lead to the drive for addicts and others to seek extraneous opiate mu stimulation). Furthermore Buprenorphine has been used by this author concurrently with Naltrexone to permit direct detoxification to an opiate blocker from injecting heroin use. Buprenorphine is safe, more flexible and potentially much more effective than Methadone: the current preference of prescribers (not patients) reflects the insecurities of our profession rather than the strenghts of our clinical tools. Competing interests: None declared |
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Chris H Ford, GP Lonsdale Medical Centre, 24 Lonsdale Road NW6 6RR
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I must disagree with Jason Lunty et al editorial saying methadone needs to be replaced by buprenorphine and question much of their case in favour of this. Methadone maintenance is one of the most successful, evidence treatments that we have in medicine today and if used correctly is both effective and safe. It has been available for many, many years and has saved many thousands of lives worldwide. Buprenorphine in contrast has only been licensed for use in treatment of dependence in UK since 1999, although longer in some other countries and is the only drug licensed for drug dependence in the UK for the last 25 years (compare this with diabetes). It is not unusual that here in the UK, where on the whole we use methadone sub-optimally, buprenorphine is seen as the solution to our problems – ‘the new kid on the block’. The evidence for it being as effective for maintenance is not there, even the 2 references that Lunty uses to support buprenorphine maintenance (his references 7 and 9) state that methadone is more effective. Buprenorphine ALONE may be a little safer in overdose but most drug users in the UK are now poly-drug users and there is no evidence that buprenorphine in combination with alcohol, cocaine and benzodiazepines is any safer than methadone in this combination. Plus don’t forget the highest death rate in people who use drugs is post detoxification. Many people, including RCGP, NTA and DH have worked hard over the past 15 years to improve treatment for people, please don’t let this one opinion based editorial damage that improvement. Competing interests: None declared |
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Adam Bakker, GP Lisson Grove Health Centre, London NW8 8EG, Vanessa Sibanda
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We very much welcomed the introduction of buprenorphine substitution treatment as an option in opiate addiction. It is reasonably popular with patients and has some advantages in specific clinical settings. However, we disagree with Luty's suggestion that burpenorphine should replace methadone(1). Doctors and patients need different treatment options in different phases of treatment and buprenorphine does not suit everyone. This is perhaps more obvious in clinical practice than in clinical trials where patients have agreed to cooperate with the research and are thus more likely to stick with their treatment.
Since January 2004 54% of the patients who started maintenance treatment with us chose buprenorphine initially. However 64% of them asked to switch to methadone within two months because buprenorphine didn't suit them. Despite the best intentions of prescribers and pharmacists, it is difficult to ensure truly supervised consumption for slowly-dissolving sublingual tablets. Evading supervised consumption is understandable since many patients continue using heroin, at least initially, and want to avoid antagonist-precipitated withdrawal. We do not discount the risks of recreational illicit methadone use but illicit buprenorpine is not hazard-free. The risk of respiratory depression might be less but the likelyhood of injecting is greater and there is still a risk of pulmonary oedema(2). Of the 167 methadone-related deaths in 2003, 75% were poly-drug deaths. Overall, opiate overdose deaths fell by 21% to 1040 compared to the previous year(3). The proportion of poly-drug deaths could have been even higher because contributory drugs are often under-reported(4). Post-mortem methadone blood levels are hard to interpret because it is lipophilic and levels can increase up to four-fold by redistribution after death whereas morphine levels show relatively little change(5). Pirnay showed the difficulty in determining methadone's role in poly-drug deaths. In 30% of methadone-related deaths other substances were also present at toxic levels whereas some of the highest methadone levels where found in cases of carbon monoxide poisoning and a firearm homicide(6). Furthermore the highest drug-related death rate in 2003 was in Brighton (3) where methadone provision was considered to be poor(7). Only a minority of addicts currently seek treatment. We feel that rather than reducing the treatment menu, treatments should be made as accessible and attractive as possible. Methadone still has the best outcomes on meta-analysis(8,9). Buprenorphine certainly has a place but so have dihydrocodeine and morphine(10). 1. Luty J, Is methadone too dangerous for opiate addiction? BMJ 2005;331:1352-3 2.Thammakupee G, Sumpatanukule P, Noncardiogenic pulmonary edema induced by sublingual buprenorphine. Chest 1994 Jul;106(1):306-8 3.Ghodse H, Schizfano F,Oyefaso A, Bannister D,Cobain K, Dryden R, et al. Drug-related deaths as reported by participating Procurator Fiscal and Coroners. London: St George's Hospital Medical School, 2004 (International Centre for Drug Policy Reports 11 and 13) 4.Zador D, Kidd B, Hutchinson S, Taylor A, Hickman M, Fahey T, et al. National Investigation into Drug Related Deaths in Scotland, 2003. Edinburgh: Scottish Executive Social Research, Substance Misuse Research Programme. 2005. 5.Drummer OH. Post mortem toxicology of drugs of abuse. Forens Science Int 2004;142:101-113 6.Pirnay S, Borron SW, Giudecelli CP, Tourneau J, Baud FJ, Ricordel I, A critical review of the causes of death among post-mortem toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths. Addiction 2004;8:978-88 7.Bennett J (Consultant in Public Health Medicine), Tackling Drug Deaths in Brighton & Hove 2004, Drug-Related Deaths Conference. 17/11/04 Manchester 8.Amato L, Davoli M, Perucci AC, Ferri M, Faggiano F, Mattick R. An overview od systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. J Subst Abuse Treat 2005 Jun;28(4):321-9 9.Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2003;(2):CD002207 10.Eder H, Jagsch R, Kraigher D, Primorac A, Ebner N, Fischer G. Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy. Addiction 2005 Aug Competing interests: None declared |
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Clive L Morrison, General Practitioner Pendyffryn Medical Group, Ffordd Pendyffryn, Prestatyn, Denbighshire. LL19 9DH
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A safer alternative to methadone is long overdue (1). An Advisory Council on the Misuse Drugs report found there had been 2,576 methadone related deaths in a five-year period (2). The Committee on Safety of Medicines have received 12 reports of fatalities with methadone, through the suspected adverse drug reactions yellow card scheme. Doctors who prescribe methadone have been complicit in under reporting. Global surveillance of deaths associated with medicines that have been recently withdrawn, such as cerivastatin, troglitazone and rofecoxib pale into insignificance when compared to methadone. Co-proxamol is due to be discontinued even though its unauthorised use is associated with far fewer deaths. Government should take similar action with methadone to protect public health. A recent Cochrane Review (3) showed that methadone treatment does not stop illicit heroin use or reduce criminality. The Department of Health guidelines on clinical management “Drug misuse and dependence” (4) admitted it was based on no more than expert committee reports and clinical experience of respected authorities of the psychiatric establishment. This is insufficient for it to be accepted as effective evidence-based health care and the current practice of methadone prescribing is a peccant policy. Doctors do not have the monopoly in the supply of methadone and benzodiazepines. Prescription drugs have street values, which are readily determined and are easily tradable. Methadone substitution therapy is an oxymoron as many drug users already have methadone as their primary drug of addiction when first presenting for treatment. In reality, methadone prescribing is the minority view amongst general practitioners and the evidence exists which suggests the UK methadone policy is an ill-conceived strategy. As buprenorphine is a novel approach its use should also be confined to specialist services. References 1 Luty J, O'Gara C, Sessay M. Is methadone too dangerous for opiate addiction? BMJ 2005;331:1352-1353 (10 December) 2 Advisory Council on the Misuse of Drugs. Reducing Drug Related Deaths - A Report by the ACMD, London: Stationery Office, 2000 3 Mattick RP, Breen C, Kimber J, Davoli M Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence (Cochrane Review) The Cochrane Library, Issue 2, 2005. 4 Department of Health. Drug misuse and dependence: guidelines for clinical management. London: Stationery Office, 1999. Competing interests: None declared |
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David O Yates, GP Cheadle Staffs, ST10 1EY
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I agree with the refreshing remarks made by Roger Weeks, and would add that it matters not a jot that subutex and methadone gets on the black market. Anyone killing themselves with these drugs has such a chaotic life that they are at high risk of doing so with something anyway. There will always be some deaths amongst such members of society. The lucky ones who survive should not be denied help when they are ready, because some of us are worried about a few prescription drugs getting in the wrong hands. Competing interests: None declared |
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Andrew Byrne, Addiction physician 75 Redfern St, Redfern, 2016, Australia, Richard Hallinan
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Dear Editor, These authors' enthusiasm for buprenorphine over methadone risks losing baby and bath water. Some patients fare well on one drug yet poorly on the other, so a choice is needed, as in depression, arthritis or hypertension. The authors write: "Without digressing further into this debate, we point out that that buprenorphine is at least as effective as methadone in both maintenance and detoxification." The references cited (as abstracts) do not support the assertion that buprenorphine is at least as effective as methadone in maintenance treatment. Most randomised control trials have showed adequate methadone doses (60-100mg/day) to be associated with modestly higher retention rates and/or lower illicit opiate use than buprenorphine, with low dose methadone (eg 20-30mg daily) clearly giving poorer results than adequate doses (ref 1). There are limits to what randomised trials can tell us about dose- response relationship in methadone maintenance, and ethical limits to the use of randomised trials of non-equivalent medications. Further, "....a finding of 'no significant difference' is often loosely interpreted to mean clinical equivalency, which it is not" (ref 2). There is other clinical evidence of a dose-response relationship in MMT extending to doses above 100mg/day (ref 3). We suggest that more research into appropriate treatment matching is needed. The authors are right to point out the risks of unsupervised dispensing of methadone. However, they assume that reducing availability of methadone will reduce overdoses, despite strong contrary evidence that increased methadone availability actually reduces overdose rates (ref 4- 11). This is not an either/or situation. Better outcomes in addiction treatments are likely to be achieved by increasing the range of treatments available. To this end there should be trials of supervised LAAM, oral morphine and/or intravenous methadone/heroin, all of which show some promise for difficult cases. The answer is not for methadone to be replaced by a more expensive and sometimes less effective alternative, but for appropriate supervision of dispensing of opioid replacement treatment, with take-home doses for people with demonstrated stability in treatment. Yours faithfully, Andrew Byrne, Richard Hallinan References: 1. Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2004;(3):CD002207. 2. Ling W, Wesson DR. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug and Alcohol Dependence 70 (2003) S49_/S57 3. Hallinan R, Ray J, Byrne A, Agho K, Attia J. Therapeutic thresholds in methadone maintenance treatment: A receiver operating characteristic analysis. Drug Alcohol Depend. 2005 Jul 15; [Epub ahead of print] 4. Grönbladh L, Öhlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand (1990) 82:223-227 5. Williamson PA, Foreman KJ, White JM, Anderson G. Methadone related overdose deaths in South Australia 1984-1994. Med J Aust 1997;166:302-305 6. Caplehorn JRM, Dalton MSYN, Haldar F, Petrenas A-M, Nisbet JG. Methadone Maintenance and Addict's Risk of Fatal Heroin Overdose. Substance Use & Misuse 1996: 31(2); 177-96. 7. Appel PW, Joseph H, Richman BL. Causes and Rates of Death Among Methadone Maintenance Patients Before and After the Onset of the HIV/AIDS Epidemic Mount Sinai Journal of Medicine (2000) 67;5/6:444-451 8. van Ameijden EJC, Langendam MW, Coutinho RA. Dose-effect relationship between overdose mortality and prescribed methadone dosage in low- threshold maintenance programs. Addictive Behaviors (1999) 24(4):559-563 9. Bryant WK, Galea S, Tracy M, Markham Piper T, Tardiff KJ, Vlahov D. Overdose deaths attributed to methadone and heroin in New York City, 1990- 1998. Addiction (2004) 99: 846-854 10. Shah N, Lathrop SL, Landen MG. Unintentional methadone-related overdose death in New Mexico (USA) and implications for surveillance, 1998 -2002. Addiction (2005) 100; 2: 176-188 11. Brugal MT, Domingo-Salvany A et al. Evaluating the impact of methadone maintenance programmes on mortality due to overdose and AIDS in a cohort of heroin users in Spain. Addiction (2005) 100:981-989 Competing interests: Dr Byrne charges a fee for dispensing maintenance opioids in his surgery. |
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ivor p hodgson, SpR in Addictions leeds addiction unit ls2 9ng
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patients who are using more than £30-£40 heroin/day find it particularly difficult to stabilise on buprenorphine, as it displaces the circulating opiates and has less potency. this gives rise to a 'partial blocking' effect. this tends to precipitate quite severe withdrawal symptoms in this group of patients when given buprenorphine as a pose to methadone (which is more potent at mu receptors). if this happens you may find your therapeutic relationship with your patient is compromised. given that the government targets include keeping patients in treatment; it is difficult to envisage there being no role for methadone in the treatment of some groups of patients. Competing interests: None declared |
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Jim L Barnard, primary care adviser Wirral CH47
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This editorial has not acknowledged the fact that comparative research between methadone and buprenorphine at optimal dosage has not been done. Thus the overwhelming evidence for the effectiveness of methadone at optimal doses means it remains the gold standard. Also research in Sheffield showed that the supply of methadone can be doubled without increasing methadone related mortality whilst overall opiate mortality decreased. Even the drug company that manufactures buprenorphine does not advocate it completely replacing methadone. The French experience shows that buprnorphine prescribing alone is not enough and consequently methadone prescribing has rapidly increased over recent years there Competing interests: None declared |
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george ryan, gp low hill medical centre,wolverhampton wv10 9sx
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This editorial demonstrates a disturbing lack of understanding of the principles which determine choosing between Methadone and Buprenorphine in the treatment of problematic opioid drug use. Treatment with Methadone is intended to alleviate withdrawal symptoms by prescribing sufficient or 'optimal' doses of the drug to this end. On the other hand, treatment with Buprenorphine is intended to achieve a blockade effect with regard to problematic opiate drug use, rather than relief of symptoms of withdrawal. This is not to disregard considerations of safety and there is a considerable body of evidence to support Methadone as a safe and effective drug when prescribed and dispensed in an appropriate way. Furthermore, the Primary Care-rooted approach, an approach which underpins all aspects of treating any chronic relapsing condition, is particularly suited to the treatment of problematic opioid drug use. An approach where one treats the individual, not just his or her drug use or illness, in an optimum, holistic way. This demands a broad and deep understanding of each and every patient and their illness or their problematic drug use, along with any issues which might underpin their problematic drug use. There is an understanding, in the Primary Care Harm Reduction approach, that to demand abstinence or perfection from patients, especially those with chronic illnesses, is, at best naive, and, at, worst subversive. It is possible, indeed, on occasions, desirable and necessary, to be pragmatic and to be so without being collusive. The authors' use of statistics is extraordinarily selective and one is tempted not to dignify it with a reply. beyond saying that if more people were prescribed more Methadone there might be fewer 'drug related deaths'- itself a term subject to a number of definitions. This editorial is a worrying example of the worst sort of opinion based medicine and merits a reply only in order to limit the damage of its simplistic, questionable and puzzling conclusions. Ultimately, it is hoist on its own petard by focusing on the drugs-albeit of treatment-rather than the patient. Competing interests: None declared |
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Gordon R. Morse, Trust Specialist West Wiltshire Specialist Drug and Alcohol Service
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Dear Sirs, I am unclear what the purpose of Luty, O’Gara and Sessay’s editorial was (BMJ 331 10 December 2005). The value of buprenorphine in the treatment of opiate dependency is clear, and to my knowledge has never been seriously challenged. By the same token, the mountain of evidence in favour of methadone treatment spanning four decades is incontrovertible. But as any one with anything more than very limited experience of treating opiate addiction will know, buprenorphine is not suited to all, not adequate for all and not appropriate to all. Buprenorphine, for all the reasons that this editorial made clear, is a most welcome addition to an otherwise very limited menu, and that is known to all. If the purpose of this editorial is to say that methadone is no longer needed, that is manifestly wrong. If it is to remind us that buprenorphine is useful, it is unnecessary. What was the point of the piece, and why did the BMJ chose to print it? Competing interests: None declared |
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Adam Bakker, GP Lisson Grove Health Centre, London NW8 8EG
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Dr Morrison has seriously misquoted the report on reducing drug related deaths by the Advisory Council on the Misuse of Drugs. There were 1598 methadone related deaths for the years 1993-97 (not 2576 as he claims) while other substances were also mentioned on 978 of these death certificates. In addition, he cannot be familiar with the 1999 guidelines if he believes that they are only based on opinion. In reality, they make extensive reference to research. They describe methadone maintenance treatment (MMT) as "one of the most researched of the available treatment modalities" and add: "an overall assessment of its effectiveness can be made with more confidence than for other treatments". The guidelines then quote some of this research. Dr Morrison's reference to the Cochrane review is to the abstract only. In the full text the authors explain: "Methadone maintenance remains one of the best-researched treatments for opioid dependence. It is the only treatment for opioid dependence which has been clearly demonstrated to reduce illicit opiate use more than no-treatment, drug-free treatment, placebo medication or detoxification in clinical controlled trials. These trials have been conducted by different research groups, in markedly differing cultural settings, yet have converged to provide similar results. [They quote 12 references]... Methadone treatment should be supported as a maintenance treatment for heroin dependence...It does not seem feasible at this stage to conduct further randomised trials of methadone treatment." (The 6 trials discussed in the review are over 16 years old.) MMT reduces mortality by 70%- 90% (1,2) in meta-analyses in a population with a mortality some 20 times higher than their peers (3). There is room for debate about how best to deliver the clear benefits of MMT, balancing stricter pickup rules against the higher dropout that such rules cause; and current average MMT doses are still disgracefully low. However, to question the benefits of adequate MMT really is to play Pope to Galileo. References: 1. Caplehorn JR, Dalton MS, Haldar F, Petrenas AM, Nisbet JG. Methadone maintenance and addicts' risk of fatal heroin overdose. Subst Use Misuse 1996 Jan;31(2):177-9 2. van Ameijden EJ, Langendam MW Coutinho RA. Dose-effect relationship between overdose mortality and prescribed methadone dosage in low-threshold maintenance programmes Addict Behav 1999;24:559-63 3.European Monitoring Centre for Drug and Drug Addiction, Annual Report 2004 http://ar2004.emcdda.eu.int/en/page079-en.html Competing interests: None declared |
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stephen brinksman, GP Ridgacre House Surgery B32 2tj
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It would seem that opinions with references should now be regarded as evidence based. I am sure that there are practitoners working in the substance misuse field who feel that buprenorphine is the only drug we should use and others who feel methadone to be superior, however the majority of us want to be able to offer a choice of treatments. The highest number of opiate related deaths is in the group who are not in treatment, narrowing our options simply excludes more patients from treatment and I fail to see how there is any benefit in this. Some patients do not tolerate buprenorphine, some do not stabilise on it and some abuse it. It is a useful drug and has been successfull in many of the patients I have used it with, however the same applies to methadone. Surely we shouldn't be debating reducing our already small number of evidence based therapies when as is evident from some responses there are still those who don't seem to think we should be prescribing at all. Competing interests: None declared |
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Jeff Fernandez, Alcohol and nursing research lead for islington PCT Islington PCT 336-348 Goswell Road, Islington, London. EC1V 7QL
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The article does indeed cide that for a treatment and a methadone naive patient 50 mls is a potentially lethal dose. However, the 'black' economy is very hard to regulate and there can only be an emphasis on safe prescribing of methadone, not only from doctors and now nurse prescribers in the NHS, but also private practices. This is what the issue is I feel, in preventing overdoses, and switching to buprenorphine will not stop unsafe and sometimes ineffective prescribing in my opinon. Also, if buprenorphine became more widely it used it too would have a street value on the 'black' economy and the same problems, if indeed less, could still occur. It was only a decade or less that the sister version of temegesic was withdrawn since injecting it created acute physical health problems and increased morbidity for injecting drug users. Another piont is the overwhelming evidence to suggest that methadone is indeed an effective treatment for opiate dependence. It has a wide applicability and range from moving towards abstinence to incorporating the model of 'harm minimisation'. It is also cheap and therefore economic for the NHS. Buprenorphine is not as economical and under researched in its outcomes in comparison. methadone prescribing is better but just needs to be taught and better regulated. However, the paper is a welcome one which has opned an effective debate in prescribing in the area of substance misuse. For this alone it is valuable. Jeff Fernandez
Competing interests: None declared |
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Michael P Scully, Consultant Psychiatrist Addictions Service, HSE South West Area, Cherry Orchard Hospital, Ballyfermot, Dublin 10, Eamon Keenan, Consultant Psychiatrist and Clinical Director
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Luty and colleagues have generated some controversy with their recent editorial. They appear to acknowledge the preeminent role of methadone in opioid substitution therapy over the last forty or so years. They bemoan how badly methadone therapies are resourced and delivered in England and Wales and suggest that this is a valid reason to move to the use of a potentially safer and more expensive agent Buprenorphine (BPN) in the continuing absence of an adequate treatment infrastructure. An alternative viewpoint is that it is high time that commissioners of opioid treatment services in England and Wales adequately resource effective systems of delivery of opioid substitution therapy. The recent experience in the Irish Republic illustrates that developing a treatment infrastructure is possible. Although methadone was licensed for the treatment of opioid dependence in the late 1960s the expansion of Addiction Services only took place in the early 1990s with the adoption of a Harm Reduction approach by the Irish Government. Substitution treatment for opioid dependence is now more widely available with approximately half of estimated 14,000 opioid users in the Republic of Ireland in substitution treatment as of November 2005. The mainstay of treatment is with oral methadone in the sugar free formulation of 1mg/ml. All patients on oral methadone are registered on a Central Treatment List maintained by the Drug Treatment Centre Board (a tertiary outpatient Addiction Treatment facility in central Dublin). All patients have a designated treatment card lodged with their community pharmacy if dispensed in the community. Community GPs and pharmacists are paid for their participation in the Methadone Protocol and are subject to an ongoing quality review process. This arrangement allows for dispensing and supervised ingestion of methadone in community settings. Methadone treatment is free for the individual patient. An innovative and resourced programme of shared Care exists between specialized Psychiatric Addiction Services, General Practice and Community Pharmacies. In general practice settings only specially trained and registered General Practitioners are allowed prescribe methadone for the treatment of opioid dependence. Level 1 trained GPs are allowed prescribe for a limited number of patients while more experienced level 2 GPs may both initiate treatment and continue to prescribe for a larger number of patients within their practices on an extended basis. Each Health Service Executive area (similar to an NHS Trust) provides services to a defined geographic catchment area. The GPs and Community Pharmacists involved in the provision of methadone in the community are supported by senior specialists from their own disciplines who work closely with the Consultant Addiction Psychiatrists and Senior Management in the Addiction Services. A Lead GP specialist coordinates GP involvement and a Lead Liaison Pharmacist coordinates with Community Pharmacies, GPs, sector Addiction Consultants and the Central Treatment List. The facility exists to transfer patients who destabilize in the community from their prescribing GP back to the specialized Addiction Treatment Services. Assuming that there is agreement that proper systems are necessary to deliver opioid substitution in the community, and that the recent Irish experience demonstrates that these systems can be developed, what advantage does BPN offer as an alternative opioid substitution agent? Luty et al state that BPN is equivalent to methadone in detoxification and maintenance treatment of opioid dependence. This is true of mild to moderate degrees of opioid dependence (i.e. conditions where up to 60mg of methadone is adequate to stabilize a patient’s opioid use but it is certainly not the case for persons with more severe degrees of dependence who may require doses from 80mg upwards).It may be that BPN may be a more appropriate agent for younger persons or those with milder degrees of dependence and in whom detoxification may be a realistic medium term goal. It seems generally accepted that BPN is a safer agent to use in the induction process than methadone in view of it‘s properties as a partial agonist. Safer induction on to methadone can be achieved if consumption is supervised on a daily basis in the clinic or community pharmacy and there is regular review by the prescribing doctor of the patient’s clinical condition. If these safeguards obtain then any risk associated with methadone induction is diminished significantly. Luty and colleagues do not make any reference to BPN’s potential side effect profile There have been recent concerns expressed about its potential effect on liver functioning in HCV positive opioid dependent patients. While the numbers involved appear small and the potential effect may be limited it does serve as a reminder that no pharmacological agent is without its potential side effects. There is also the issue of diversion of prescribed BPN to the black market. Significant levels of diversion and reported injecting use have been reported in the professional literature in those European countries where it is commonly used. Diversion and injecting use has significant implications for the health of those involved. It may be that the combined BPN naloxone preparation will offer significant advantages in terms of minimising the potential for injecting use of diverted BPN. The question of costs is mentioned by Luty and Colleagues. In an Irish context a recent pharmacoeconomic evaluation indicated that at 12 and 24 months BPN maintenance was twice as expensive as methadone maintenance. A move to a more widespread use of BPN as a substitution agent at this point in time would necessarily incur significant costs for services. In conclusion we do not believe that Luty and colleagues have made the case for the adoption of BPN in preference to methadone as the substitute of choice in opioid replacement therapy for opioid dependence. We consider that the focus of professional agitation should be to obtain sufficient funding and political agreement to improve opioid delivery systems in England and Wales. Methadone is safe and effective if employed in adequately resourced treatment systems. The proposed adoption of BPN as suggested by Luty et al as the mainstay of opioid substitution treatment will not and cannot compensate for the lack of investment in delivering safe opioid delivery systems for persons on opioid substitution treatment. References Barry, J. (2002) Policy response to opioid misuse in Dublin. Journal of Epidemiology and Community Health, 56, 7-8. Keenan, E. & Barry, J. (1999) Republic of Ireland has set up scheme to regulate methadone prescribing by GPs. BMJ, 319 1497. National Advisory Committee on Drugs. (2002) Use of Buprenorphine as an intervention in the treatment of Opiate Dependence Syndrome. Stationary Office, Dublin. Competing interests: None declared |
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Susi R Harris, Clinical Lead in Substance Misuse Calderdale Substance Misuse Service
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Dr Luty and colleagues have supplied a useful reminder about the safety of buprenorphine over methadone and the need not to let cost considerations override best practice treatment decisions. They go so far as to advocate buprenorphine as the treatment of choice for opiate dependency on grounds of safety. However, it is not actually possible to force a patient to accept a treatment they do not like - they will (and often do) simply stop taking it. The patient must make the choice, not only for ideological reasons but also for the pragmatic one that it is the best way to ensure they are retained in treatment. Our job is not to determine the treatment but to give adequate information for the patient to make the right choice for them. The choice of medication is only one factor in determining the success of treatment. Psychosocial support has been shown to be a potent enhancer of the efficacy of medication, (ref 1) and can begin as soon as the patient engages in treatment, of whatever sort. Methadone has an extremely valuable role in engaging patients into treatment who would otherwise remain untreated. Because of the blockade effect of buprenorphine (referred to in other responses, but not, curiously, by Dr Luty) many patients cannot sustain taking buprenorphine because they are not yet ready to give up heroin. But even while patients continue to use street drugs for a time, treatment is nonetheless working and improving health, for the patient and for society at large. Evidence shows there are substantial gains, from reduction in risky injecting behaviour (ref 2) and blood-borne virus transmission (ref 3) to reduction in illicit drug use and crimiality (ref 4, 5) with relatively very low NNT scores (ref 6) , meaning that methadone treatment for drug misuse compares favourably with many of the other pharmacological agents used in medicine today. Even if future evidence shows similar gains for buprenorphine, there would be patients who could not take it, and it would be wrong to deny this cohort of patients such a valuable intervention as methadone can offer, not to mention society at large who will pay a high price in criminal justice, healthcare, social care and occupational costs for their untreated opioid addiction. Dr Luty and coleagues are right to point out that buprenoprhine is just as prone to diversion as methadone. There is already a black market for the drug, particularly in prisons, and it is often surreptitiously spat out, crushed and snorted via the nasal mucosae, as well as being injected, the latter route carrying a high risk of septicaemia and endocarditis from mouth bacteria). In some states in Australia, where the problem has also been noted, (ref 7) all buprenoprhine prescribed to be taken under supervised consumption is crushed prior to administration in order to prevent this. Crushing also speeds up absorption, and can thus overcome the problems encountered by pharmacists described in the rapid response by Graham Brack. The National Pharmaceutical Association in the UK has recently agreed to indemnify all pharmacists who administer buprenorphine crushed according to its protocol. (ref 8) 1. McLellan A T, Arndt I O, Metzger D S, Woody, G E, O Brien, C P, The effects of psychosocial services in substance abuse treatment Journal of the American Medical Association 269(15); 1953-60 2. Ward J, Mattick R, Hall W, Methadone maintenance treatment and other opioid replacement therapies, 1998, Harwood Academic Publishers 3. Metzger DS et al, Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18-month prospective follow-up. Journal of Acquired Immune Deficiency Syndromes, 1993, 6(9) 1049-56 4.Gossop M, Marsden, J, Stewart D, NTORS after five years: The National Treatment Outcome Research Study <www.ntors.org.uk> 5. Marsch L A, (1998) The efficacy of methadone maintenance interventions in reducting illicit opiate use, HIV risk behaviour and criminality: a meta- analysis, Addiction 93:4 515-32 6. Methadone maintenance interventions Bandolier Aug 1999; 66-6 <http:// www.jr2.ox.ac.uk/bandolier/band66/b66-6.html> 7. <http://www.mja.com.au/public/issues/176_04_180202/cla10539.html> accessed on 20.12.05 8. The Pharmaceutical Journal, Vol 274 No 7343 p401, 2 April 2005 Competing interests: None declared |
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Clive L Morrison, General Practitioner Pendyffryn Medical Group, Ffordd Pendyffryn, Prestatyn, Denbighshire. LL19 9DH
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For clarification the following quote is taken directly from the foreword of the guidelines, page xiv. “They are primarily based on evidence obtained from expert committee reports and the clinical experience of respected authorities. Written evidence was sought and received from a wide range of medical and non-medical bodies, and individual professionals working in this field.” Table 7.1 of type of methadone deaths on page 61 of the report “Reducing Drug Related Deaths” is unclear but suggests 1598 is the accurate figure, although it is a minimum number as it does not include any deaths in Northern Ireland or the substantial number in Scotland. Presumably the authors did not provide a convenient totals figure in an attempt not to be too alarming. Whether it’s either, more than 1598, or the 167 preventable deaths over a shorter period, it still remains wholly unacceptable. For a prescription drug that is lethal to so many drug users, its use as a treatment should only be recommended on the most robust of evidence, which is that obtained from RCT’s. It is misguided to rely upon the often- quoted observational studies, which are confounded by the regression-to- the-mean effect. Recruits to studies, that are new to treatment are the drug users in most desperate need and are likely to improve no matter what kind of intervention is offered. It is concerning that health resources are funding methadone programmes that are shown not to result in drug free outcomes and compound problems by adding methadone to the pool of illicit drugs. To prescribe methadone to a user, who continues to use illicit opiates, albeit at reduced quantities, is not a desirable health-orientated outcome or gain. Even the RCT’s have not included the effects on the community from the spill of methadone and cost/benefit-analysis studies would never countenance the associated death rates. Grants awarded for such studies are tendered for by the very centres (or affiliated to) which provide drug services; I am not aware of any independent studies in the UK. It is with little wonder then, that there have been no recent trials that would have the potential to counter argue against the current NHS structure, which has had much political and financial investment. Several doctors have recently been under investigation for drug dependency treatment (1) and many of the criticisms made against heroin prescribing are also relevant to methadone. In the current climate there is greater surveillance of deaths related to doctors’ prescriptions (2) and doctors have a duty of care even if it is indirect. Some may find they are the focus of investigating authorities if it is determined that their practice was not a council of perfection, in being unable to eliminate illicit methadone supplies in their locality. References 1 Dyer O Seven doctors accused of failing to monitor health of addicted patients BMJ 2004; 329: 818 2 Clarke-Jones J Why I’m a victim of Shipman era Pulse. 17 December 2005 page 1 Competing interests: None declared |
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Oliver WC Morgan, PhD Student Imperial College, W6 8RP, Clare Griffiths and Matthew Hickman
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In their editorial 1, Luty et al incorrectly reported that in 2003 there were 167 drug related deaths involving methadone in Britain. Published statistics from the Office for National Statistics (ONS) and the General Register Office for Scotland show there were actually 262 methadone-related deaths in Britain (175 in England and Wales 2 and 87 in Scotland 3). This discrepancy occurred because Luty et al used data from np-SAD (National Programme on Substance Abuse Deaths 4), which is based on voluntary returns from just 80% of coroners, rather than all deaths that meet the current National Statistics definition for drug poisoning 5. The number of deaths citing buprenorphine was also incorrect. The Drug Poisoning Mortality Database at ONS includes six deaths involving buprenorphine. Two deaths occurred before buprenorphine was licensed for opiate dependence in 1999. No other drugs were mentioned for these deaths on the coroner’s death certificate following inquest. There were a further two deaths in 2002 and two more in 2003. All mentioned other drugs: Temazepam (n=2), Diazepam (n=1), Codeine (n=1), Dothiepin (n=1) and Heroin/Morphine (n=1). Additionally, Luty et al have overestimated the death rate per million methadone prescriptions. Firstly they inflated the numerator by using deaths in Britain but prescription data for England. Secondly, they inflated the numerator further by using the total number of methadone deaths. However, as Luty et al point out, like buprenorphine, other drugs are also found in a sizeable proportion (39%) of deaths where methadone is detected and hence some of these deaths may not have been due to methadone. Thirdly, using methadone prescriptions as an estimate of methadone usage will have underestimated the denominator because methadone is prescribed in a wide range of doses and for instalment dispensing (i.e. large quantities issued on one prescription). In previous work on fatal antidepressant poisoning, we found that when introduced, the newer antidepressant drugs had a low ratio of deaths to prescriptions 6. However, as these drugs became increasingly popular, the number of deaths increased more than might have been expected from the original number of deaths per million prescriptions. By 2001, the newer antidepressants (principally Venlafaxine) had a higher ratio of deaths per million prescriptions than SSRIs. This highlights the need for caution when making statements about safety of drugs that have not been widely used and for which we have only a few years of data. 1. Luty J, O'Gara C, Sessay M. Is methadone too dangerous for opiate addiction? BMJ 2005;331:1352-3. 2. ONS. Report: deaths related to drug poisoning: England and Wales, 1999-2003. Health Stat Q 2005;25:52-9. 3. Registrar General Office for Scotland. Drug-related Deaths in Scotland in 2003. Available at: http://www.gro- scotland.gov.uk/statistics/library/drug-related-deaths/03drug-related- deaths.html 2004. 4. Ghodse H, Schizfano F, Oyefesom A, Bannister D, Cobain K, Dryden R. Drug-related deaths as reported by participating Procurator Fiscal and Coroners. London: St George's Hospital Medical School, 2004 (International Centre for Drug Policy Report 13). 2004. 5. Christophersen O, Rooney C, Kelly S. Drug-related mortality: methods and trends. Popul Trends 1998;93:29-37. 6. Morgan O, Griffiths C, Baker A, Majeed A. Fatal toxicity of antidepressants in England and Wales, 1993-2002. Health Stat Q 2004;23:18- 24. Competing interests: None declared |
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Marina Davoli, Coordinating Editor Drugs and Alcohol Review Group Department of Epidemiology ASL RM E Via S. Costanza 53 00198 Roma, Laura Amato, Simona Vecchi, Pier Paolo Pani, Carlo A Perucci
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Dear Editor, the editorial under debate is a clear example of biased reporting of the available evidence, as already underlined by other rapid responses. The Authors of this editorial emphasise the effectiveness of buprenorphine claiming that “it is at least as effective as methadone” and to support this message they quote just one Cochrane Review (1). The authors fail to quote other two Cochrane Reviews, the one on detoxification treatment (2) reports that there are no differences between buprenorphine and methadone on completion of treatment and intensity and duration of withdrawal treatment, the other on maintenance treatment (3) clearly shows that methadone is better than buprenorphine in retaining patients in treatment and in reducing illicit drug use. Unfortunately data on safety are very poor, randomised controlled trials are often not able to detect significant differences, and most of the evidence comes from case series and not always comparable populations; eventually, there is no sound evidence suggesting to replace a cheap and effective treatment such as methadone with a more expensive and less effective treatment such as buprenorphine. Buprenorphine enlarges the range of treatments available for opioid addiction. However, its use cannot be based on commercial, ideological or political resistance to the use of proper methadone treatment. If this is the case this should be done explicitly against the available evidence and not quoting only a partial evidence. Moreover, as far as mortality attributable to diversion of methadone is concerned, it seems at least questionable that deaths occurring mostly among people out of treatment, because of diversion of methadone, should impair the use of methadone among treated patients, rather we would suggest that it calls for more proper and responsible use of treatment for opiate dependence in the different treatment settings. References 1.Gowing L, Ali R, White J. Buprenorphine for the management of opioid withdrawal. The Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD002025. DOI: 10.1002/14651858.CD002025.pub2. 2. Amato L, Davoli M, Minozzi S, Ali R, Ferri M. Methadone at tapered doses for the management of opioid withdrawal. The Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003409. DOI: 10.1002/14651858.CD003409.pub3. 3.Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. The Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD002207. DOI: 10.1002/14651858.CD002207.pub2. Competing interests: None declared |
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John Robson, General Practitioner London E146pG
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Before prescribing buprenorphine at three times the price of methadone, we might ask the following questions. Is there substantial trial evidence that it is more effective than methadone in promoting abstinence, long term maintenance, quality of life, reduced infection or criminality? The evidence shows no such benefit(1-3). The case for buprenorphine rests entirely on claims of greater safety. But one of the indications for buprenorphine is a degree of stability in opiate usage and people who convert to buprenorphine may have less risky life-styles than those who remain on methadone or who remain outside treatment programmes. French use of buprenorphine coincided in 1996 with liberalisation of medical prescribing for heroin addicts, previously confined to a few specialised clinics. This was associated with claims of a three fold reduction in drug related crime, a reduction in HIV infection and a decline in opiate deaths (4). However these changes may be as much to do with liberalisation policies as with buprenorphine. In France from 1994 to 1998 buprenorphine and methadone related deaths were said to total only 46! The methadone related death rate fell substantially though numbers of deaths remained much the same. In contrast, buprenorphine related deaths increased in this period and rates may have increased in 1998. In France in 1998 there were an estimated 7/10000 deaths related to methadone and 2/10000 to buprenorphine (5). In the UK in 2003 estimated rates were well below this with 1.12/10000 for methadone versus 0.22/10000 for buprenorphine relating to 167 methadone and 7 buprenorphine.related deaths (6). These figures are contested and highlight major inconsistencies both in national definitions of death and in the nature of the population using either methadone or buprenorphine. Nor are we given data on trends in overall opiate related deaths. In the UK there have been huge efforts to convert users from injectable methadone tablets to linctus and move to supervised consumption. Buprenorphine (available only in tablet form) is easily and extensively diverted and injection is endemic in France and elsewhere. In Australia this is associated with major limb infections and thromboses(7). In the absence of good evidence of either effectiveness or improved safety, why should we pay three times the price for a drug that is no more effective, more likely to be diverted, more likely to be injected and has an uncertain saftey record? Hopefully good trial evidence of both benefit and harm will replace well intentioned anecdote and someone will appraise international trends in deaths associated with substance misuse in a more detailed manner. However, before we replace one unsatisfactory drug with another we need to have clear evidence of net benefit. 1.Mattick RP, Ali R, White JM, O'Brien S, Wolk S, Danz C. Buprenorphine versus methadone maintenance therapy: a randomized double- blind trial with 405 opioid-dependent patients.Addiction. 2003;98:441-52. 2. Amato L, Davoli M, Ferri M, Gowing L, Perucci CA. Effectiveness of interventions on opiate withdrawal treatment: an overview of systematic reviews. Drug Alcohol Depend. 2004;73:219-26 3. Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2003;(2):CD002207. 4. International Centre for the Advancement of Addiction Treatment. France 2004.http://www.opiateaddictionrx.info/addiction/addiction03_france.html. Accessed 1.1.06. 5. Auriacombe M, Franques P, Tignol J. Deaths attributable to methadone vs buprenorphine in France. JAMA 2001; 285:45 6. Luty J, O'Gara C, Sessay M.Is methadone too dangerous for opiate addiction? BMJ 2005; 331: 1352 – 1353. 7. Jenkinson RA, Clark NC, Fry CL, Dobbin M. Buprenorphine diversion and injection in Melbourne, Australia: an emerging issue? Addiction 2005;100:197-205. Competing interests: John Robson is a general practitioner who prescribes methadone to his patients |
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Swapna Patankar, Registrar, Obstetrics and Gynaecology Tameside General Hospital, Fountain street, Ashton-under-Lyne, Lancashire. OL6 9RW., A.J.S. Watson, D.Cardell, G.Martin, I.Telfer
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Dear Editor, I support their {Jason Luty et.al. (BMJ 2005; 331: 1352-1353)} case in favour of buprenorphine. We have noticed its beneficial effect in pregnant drug addicts in terms of neonatal outcome. The use of illicit substances such as cocaine and heroin during pregnancy is common. In a study, anonymous screening of consecutive urine samples, of pregnant women from a UK inner-city clinic demonstrated that approximately 16% of the women had taken one or more illicit substances (1). Neonatal withdrawal symptoms occur in 55–94% of neonates exposed to opiates in utero (2). Substitution therapy is usually with methadone or buprenorphine. We conducted a retrospective observational study from December 2003 – January 2005. Antenatal patients with a history of substance misuse were stabilized on methadone or buprenorphine, depending on patient choice and compliance with the prescribed drug. The patients with polydrug use were excluded. The outcome measured was- admission to neonatal intensive care unit (NICU) for withdrawal symptoms. Out of 26 patients, 21[ 80.76%] took methadone at a mean dose of 45mls [20- 95mls] and 5 [19.24%] took buprenorphine, the mean dose being 7.36 mg [0.8- 12mg]. In the methadone group, 6 babies were admitted to NICU for treatment of withdrawal symptoms. There were no NICU admissions in buprenorphine group. Our case series demonstrated that buprenorphine is safer than methadone for antenatal opioid addiction. References: (1)Sherwood, R. A., Keating, J., Kavvadia, V. et al (1999) Substance misuse in early pregnancy and relationship to fetal outcome. European Journal of Pediatrics, 158, 488–492 (2)American Academy of Pediatrics Committee on Drugs (1998) Neonatal drug withdrawal. Pediatrics, 101, 1079–1088 Competing interests: None declared |
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Billy Boland, Clinical Lecturer in Addictive Behaviour Section of Addictive Behaviour, St George’s, University of London, Cranmer Terrace, London, SW17 0RE, Fabrizio Schifano - Senior Lecturer in Addictive Behaviour, Colin Drummond - Professor in Addiction Psychiatry.
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Dear Sir, Luty and colleagues assert that ‘Buprenorphine has not been cited in any drug related deaths reported to coroners in England and Wales since it was licensed for the treatment of opiate dependence in 1999.’(1) In fact, during the period 1980-2002 buprenorphine was identified by coroners in 43 fatalities, including 7 cases in which it was the sole substance identified. Since the introduction of higher dose buprenorphine in 1999 there has been an increase in the number of buprenorphine related deaths(2). Also, questions remain over the relative effectiveness of methadone and buprenorphine treatment for opiate dependence. In addition to some of the positive findings, some work has suggested that buprenorphine is less effective than methadone(3). Meta-analysis has shown that individuals treated with buprenorphine are 1.26 times more likely to drop out of treatment, and 8.3% more likely to have a positive urine test for illicit opiates than in methadone treated patients(4). There are also some concerns about the abuse potential of buprenorphine. Strang has previously reported the abuse of buprenorphine in the form of intravenous (IV) Temgesic formulated for sublingual use(5). Extensive buprenorphine use was reported in Scotland during the late 1980’s and 1990’s. Morrison reported this as the 3rd most popular IV drug(6). Luty and colleagues did not mention that The National Institute for Clinical Excellence (NICE) is currently evaluating the relative effectiveness of methadone and buprenorphine (7). This review will examine a range of outcomes including drug-related morbidity and mortality, changes in illicit drug use and adverse effects of treatment(8). Also, importantly, the NICE review aims to establish the relative cost effectiveness of these two treatments which will be a key consideration in making clinical and commissioning decisions. Overall we believe that many of Luty et al’s conclusions concerning the relative safety and efficacy of methadone and buprenorphine overstate the case in favour of buprenorphine. Their review pre-empts the findings of a more comprehensive and systematic review by NICE which is currently underway. 1. Luty, j., O’Gara, C., Sessay, M. (2005) Is Methadone too dangerous for opiate addiction? BMJ 331, 1352-3. 2. Schifano, F., Corkery, J., Gilvarey, E., Deluca, P., Oyefeso, A., Ghodse, A. H. (2005) Buprenorphine mortality, seizures and prescription data in the UK, 1980-2002. Hum Psychopharmacol Clin Exp 20, 1-6. 3. Kosten, T., Shottenfeld, R., Ziedonis, D., Falcioni, J. (1993) Buprenorphine versus methadone maintenance for opioid dependence. Journal Nervous Mental Disorders 181, 358-64. 4. Barnett, P., Rodgers, J., Bloch, D., (2001) A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence. Addiction 96, 683-90. 5. Strang, J. (1985) Abuse of buprenorphine. The Lancet Sept 28, 725 6. Morrison, V. (1989) Psychoactive substance use an related behaviours of 135 regular illicit drug users in Scotland. Drug and Alcohol Dependence 23, 95-101. 7. http://www.nice.org.uk/page.aspx?o=207022 8. http://www.nice.org.uk/pdf/final_scope_methadone_and_buprenorphine.pdf Competing interests: None declared |
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Linda D Harris, Director RCGP Substance Misuse Unit, Suite 314 Frazer House 32 - 38 Leman Street, London, E18EW, Chris Ford, Mark B Gabbay, Jenny Keen
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The editorial in December 10th BMJ “Is methadone too dangerous for opiate addiction” which makes a series of arguments for the consideration of buprenorphine as the main drug of choice in the treatment of opioid dependence is, in our opinion, seriously flawed. Since the publication of the Department of Health Guidelines (1) and significant investment in substance misuse treatment as part of the Government’s drugs strategy the numbers of individuals accessing treatment for drug dependence have risen significantly, assisting the government to achieve its challenging target of doubling the numbers in treatment by 2008. Within this context, clinicians responsible for advising DATs on drug treatment interventions are faced with the dilemma of balancing the need to deliver within national guidelines, offer genuine service user choice and access to services, whilst maintaining safety and best value. Whilst the authors make some valid points, the balance of advantage is by no means all in favour of buprenorphine. Recent studies (2) demonstrate similar efficacy between methadone and buprenorphine for maintenance in retaining patients and suppressing illicit drug use, but only at average UK methadone doses, which are low. There are as yet no studies comparing higher dose buprenorphine with optimal dose (between 80-120 mg) methadone and methadone still remains the gold standard for maintenance and this alone should prevent buprenorphine being adopted wholesale as the first line treatment for all opioid users. As the authors point out, buprenorphine also has its problems: firstly buprenorphine is highly soluble and injectable. The French experience suggests its safety profile is less impressive when it is injected, especially as part of poly-drug abuse which is now the norm (3). Secondly the higher dispensing fees, and length of time to observe its dispensation and our clinical experience (in the absence of research data) that it is relatively less effective among longer –term drug users suggest a policy to switch to Buprenorphine as first choice substitute treatment is premature in the light of existing evidence Experienced clinicians and nurses working in secure environments and supporting criminal justice treatment programmes such as the Drugs intervention Programme report increasing evidence of leakage, resonating with increasing international evidence (4). Given the significant health risks associated with intravenous drug use, the fact that buprenorphine is so much more easily injected than methadone mixture must be weighed against its better safety profile in overdose when the balance of harm reduction is being considered. This better safety profile in overdose is only maintained when taken alone, without alcohol, cocaine or benzodiazepines, which is frequently not the case. Consensus, supported by evidence suggests that the determining the cause of death in overdose is complex but is usually related to multiple substance use(5). The RCGP’s Substance Misuse Unit works closely with the Department of Health and other organisations with responsibility for quality of care of substance misusers and this has included supporting the development of guidance documents on the use of buprenorphine (6) and methadone (7) to enhance the management of opioid dependence in primary care. Many of its members have and continue to contribute to the literature and evidence base that underpins current service models. Guidance documents have welcomed the advent of buprenorphine as an alternative medication in a field where pharmacological options are very few, but not as the treatment of first choice for the majority. The evidence base in favour of buprenorphine compared to methadone remains thin (8). It is against this backdrop that we were surprised and dismayed that the Luty article failed to place the pharmacological management of opioid dependence within the much wider harm reduction context of drug treatment and in particular failed to highlight the significant role methadone has played in reducing drug related deaths year on year for last five years, whilst the numbers of individuals treated with methadone and the overall doses of methadone have risen. Methadone has repeatedly been shown to reduce drug-related deaths by a factor of around 7 (9,10 ). Furthermore a large study of methadone maintenance treatment in New York (11) mirrored the smaller scale findings from Sheffield, UK (12 ) in which no increase in methadone-related deaths accompanied large increases in numbers of people on methadone maintenance treatment over a period of several years. The study of the impact of buprenorphine on drug-related deaths is by comparison in its infancy. Local confidential enquiries into drug related deaths are to be encouraged and the National Treatment Agency have published guidance on setting up such enquiries as a local means of identifying ways of reducing deaths attributable to drug misuse. Interventions such as these along with the introduction of prison throughcare and aftercare schemes, overdose prevention resuscitation training of clients and carers are also vital elements of the harm reduction jigsaw. The article unfortunately painted a picture where the safety profile of the pharmacological interventions appeared to dominate the treatment plan for the service user, despite the messages in the NTA’s treatment effectiveness strategy advocating and equal emphasis on throughcare and wraparound service provision to secure positive outcomes for service users. The need to offer and retain ever increasing numbers of problematic drug users in treatment to improve their health and well being is overwhelming and the ability to offer a choice of substitute medications within models of care proven to reduce harm and improve public health is the common goal. Substitution therapy is one small part of the treatment package. If we are to achieve these goals we need as extensive an armoury of potential pharmacological interventions as possible Most importantly, service users will be at high risk if lost to treatment owing to narrowing of the treatment options. Methadone is a life-saving medication with an impressive evidence base which can be prescribed and dispensed safely to large numbers of drug users and which is known to bring about improvements in health and well- being, reduction in crime as well as huge reductions in drug-related deaths. Buprenorphine is a useful addition to the range of prescribing options for opioid users. Like all medications it has advantages and disadvantages and it will suit some clinical situations but not all. There is a clear need for further research. The National Institute for Health and Clinical Excellence (NICE) is currently examining the issue and whilst we await its findings, we should beware of throwing out the baby with the bathwater. Yours Sincerely, Dr Chris Ford, General Practitioner, Dr Linda Harris General Practitioner, Dr Jenny Keen General Practitioner, Dr Mark Gabbay General Practitioner, On behalf of the RCGP Substance Misuse Unit . All enquiries to Dr Linda Harris, Project Director RCGP Substance Misuse Unit Competing interests: The RCGP Substance Misuse Unit has received an educational grant from Schering Plough in support of events provided to its regional clinical leads Both Schering Plough and Martindale have provided educational grants to support the production of RCGP sponsored guidance documents References 1.Drug Misuse and Dependence: guidelines on clinical management. London: HMSO, 1999. 2. Mattick RP, Ali R, White JM et al. Buprenorphine versus methadone maintenance therapy: a randomised double-blind trial with 405 opioid- dependent patients. Addiction 2003; 98: 441-452. 3. Auriacombe M Fatseas M Dubernet J Aalouede JP Tignol J French field experience with Buprenorphine Am J Addiction 2004 ; 13 suppl 1 :17- 28 4. Jenkinson RA, Clark NC, Fry CL, Dobbin M. Buprenorphine diversion and injection in Melbourne, Australia: an emerging issue? Addiction 2005; 100: 197-205. 5. Milroy C M. Forrest A R W. Methadone deaths@ a toxicological analysis J Clin Pathol 2000; 53:277 - 281 6. .RCGP Guidance for the use of buprenorphine for the treatment of opioid dependence in primary care 2nd edition 2004 7. RCGP Guidance for the use of methadone for the treatment of opioid dependence in primary care 2005 8. RP Mattick, J Kimber, C Breen, M Davoli Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence The Cochrane Database of Systematic Reviews 2005 Issue 4 9. Gronbladh L, Ohland M.S, Gunne L. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatria Scandinavica 1990; 82: 223-227. 10. Brugal MT, Domingo-Salvay A et al. Evaluating the impact of methadone maintenance programmes on mortality due to overdose and AIDS in a cohort of heroin users in Spain. Addiction 2005; 100: 981-989. 11. . Bryant WK, Galea S, Tracy M et al. Overdose deaths attributed to methadone and heroin in New York City, 1990-1998. Addiction 2004; 99: 846-854. 12.. Keen J., Oliver P., Mathers N. Methadone maintenance treatment can be provided in a primary care setting without increasing methadone- related mortality: the Sheffield experience 1997-2000. British Journal of General Practice 2002; 52: (478) 387-389. Competing interests: The RCGP Substance Misuse Unit has received an educational grant from Schering Plough in support of events provided to its regional clinical leads. Both Schering Plough and Martindale have provided educational grants to support the production of RCGP sponsored guidance documents. |
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Kristan E Hilchey, Medical Technologist MAINE, United States 04856
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I would like to thank Dr. Roger Weeks for his compassionate and "on the money" reply to the editorial "Is Methadone Safe for Opiate Addiction Treatment?". As a medical professional with a long term opiate addiction, now being treated with high dose methadone, I can only say: "I wish I could find a doctor in the US that is so rational and passionate about my plight" For the past year and a half of treatment with methadone, my life has (at last) become what I always KNEW it could be, if I could JUST get some semblance of control over my addiction. If methadone were to be replaced NOW, by the much less effective bu | |||