BMJ 2014;348:g1531 doi: 10.1136/bmj.g1531 (Published 14 February 2014)
Page 1 of 2
Views & Reviews
VIEWS & REVIEWS FROM THE FRONTLINE
Bad medicine: nalmefene in alcohol misuse Des Spence general practitioner, Glasgow group—people who consumed an average of 13.5 units a day (consider also that only 60% of actual alcohol consumption is actually reported).7 Even among these problem drinkers the benefit of nalmefene was a reduction of just 1-2 units of alcohol a day, three heavy drinking days, and one additional dry day a month.6 Changes in liver function test results were minimal.6 Are these gains clinically significant?
Both Glasgow and medical school were hard drinking gigs. I enjoy alcohol and drink it for its psychoactive effect rather than for its taste or supposed health benefits. Indeed, for many years I have also struggled with smoking. Addiction is complex, with many facets, both physical and psychological, that are common to us all. I use routine, work, and responsibility to keep my own addictive tendencies in check. Today Glasgow remains a city blighted by addiction: drink, illicit and prescription drugs, gambling, and the rest. I may be a generalist, but I am also an expert on addiction.
Nalmefene (traded as Selincro, Lundbeck) has recently been approved for alcohol misuse by the Scottish Medicines Consortium1 and is under consideration by the National Institute for Health and Care Excellence.2 The decision was based on three studies funded by Lundbeck that found a 60% reduction in “high drinking risk level,” defined as drinking more than 60 g/day (7.5 units) for men or 40 g/day (5 units) for women.3 4 This significant reduction has the potential to help many people—and is a huge business opportunity. We now have a sponsored educational bandwagon promoting nalmefene in Scotland and a gathering army of salespeople.
But the devil is in the detail. Participants in these studies also received extensive additional counselling, and drinking among the placebo group dropped similarly. The company used a poorly defined primary outcome called “heavy drinking days,” reporting a two day reduction a month compared with placebo, but the hard outcome benefits were tiny—just 0.6 to 1.4 units a day, with no difference in the number of “non-drinking days.”3-5 The dark art of subgroup analysis was used to try to improve these numbers.6 This reanalysis was of a heavier drinking
Lundbeck’s analysis suggested that nalmefene was cost effective. Oddly this statistical modelling projected benefits over five years1 despite the study lasting only 12 months. Nalmefene costs £84 (€100; $140) a month.8 Another opioid antagonist, naltrexone, has a much stronger research base9 and costs a quarter of the price.8 So where is the head to head research between nalmefene and naltrexone? Who is responsible for interpreting the research in our public institutions, approving drugs like nalmefene on such questionable evidence? What is the opportunity cost? Surely these resources would be better spent improving alcohol counselling services? The drugs in alcohol addiction have tiny benefits and are a distraction from the real challenges of limiting the availability and increasing the cost of alcohol. This bad medicine is all too familiar. Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. 1 2 3 4 5 6
7 8
Scottish Medicines Consortium. Nalmefene 18 mg film-coated tablets (Selincro®). 2013. www.scottishmedicines.org.uk/files/advice/nalmefene_Selincro_FINAL_September_2013_ website.pdf. National Institute for Health and Care Excellence. Single technology appraisal. Nalmefene for reducing alcohol consumption in people with alcohol dependence. 2014. www.nice. org.uk/nicemedia/live/14317/66222/66222.pdf. Gual A, ESENSE 2 Study Group. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol 2013;23:1432-42. Mann K, Bladström A, Torup L, Gual A, van den Brink W. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013;73:706-13. Safety and efficacy of nalmefene in patients with alcohol dependence (SENSE). http:// clinicaltrials.gov/ct2/show/results/NCT00811941?term=Sense+nalmefene&rank=1& sect=Xd8k96015#outcome8. Van den Brink W, Aubin HJ, Bladström A, Torup L, Gual A, Mann K. Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies. Alcohol Alcohol 2013;48:570-8. Boniface S, Shelton N. How is alcohol consumption affected if we account for under-reporting? A hypothetical scenario. Eur J Public Health 2013;23:1076-81. Nalmefene. British National Formulary. 2014. www.medicinescomplete.com/mc/bnf/current/ PHP33535-nalmefene.htm.
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Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g1531 doi: 10.1136/bmj.g1531 (Published 14 February 2014)
Page 2 of 2
VIEWS & REVIEWS
9
McAvoy BR. Naltrexone effective for alcohol dependence. Cochrane Primary Health Care Field 2010. www.cochraneprimarycare.org/pearls/naltrexone-effective-alcohol-dependence.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Cite this as: BMJ 2014;348:g1531 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
Page 1 of 2
Views & Reviews
VIEWS & REVIEWS FROM THE FRONTLINE
Bad medicine: nalmefene in alcohol misuse Des Spence general practitioner, Glasgow group—people who consumed an average of 13.5 units a day (consider also that only 60% of actual alcohol consumption is actually reported).7 Even among these problem drinkers the benefit of nalmefene was a reduction of just 1-2 units of alcohol a day, three heavy drinking days, and one additional dry day a month.6 Changes in liver function test results were minimal.6 Are these gains clinically significant?
Both Glasgow and medical school were hard drinking gigs. I enjoy alcohol and drink it for its psychoactive effect rather than for its taste or supposed health benefits. Indeed, for many years I have also struggled with smoking. Addiction is complex, with many facets, both physical and psychological, that are common to us all. I use routine, work, and responsibility to keep my own addictive tendencies in check. Today Glasgow remains a city blighted by addiction: drink, illicit and prescription drugs, gambling, and the rest. I may be a generalist, but I am also an expert on addiction.
Nalmefene (traded as Selincro, Lundbeck) has recently been approved for alcohol misuse by the Scottish Medicines Consortium1 and is under consideration by the National Institute for Health and Care Excellence.2 The decision was based on three studies funded by Lundbeck that found a 60% reduction in “high drinking risk level,” defined as drinking more than 60 g/day (7.5 units) for men or 40 g/day (5 units) for women.3 4 This significant reduction has the potential to help many people—and is a huge business opportunity. We now have a sponsored educational bandwagon promoting nalmefene in Scotland and a gathering army of salespeople.
But the devil is in the detail. Participants in these studies also received extensive additional counselling, and drinking among the placebo group dropped similarly. The company used a poorly defined primary outcome called “heavy drinking days,” reporting a two day reduction a month compared with placebo, but the hard outcome benefits were tiny—just 0.6 to 1.4 units a day, with no difference in the number of “non-drinking days.”3-5 The dark art of subgroup analysis was used to try to improve these numbers.6 This reanalysis was of a heavier drinking
Lundbeck’s analysis suggested that nalmefene was cost effective. Oddly this statistical modelling projected benefits over five years1 despite the study lasting only 12 months. Nalmefene costs £84 (€100; $140) a month.8 Another opioid antagonist, naltrexone, has a much stronger research base9 and costs a quarter of the price.8 So where is the head to head research between nalmefene and naltrexone? Who is responsible for interpreting the research in our public institutions, approving drugs like nalmefene on such questionable evidence? What is the opportunity cost? Surely these resources would be better spent improving alcohol counselling services? The drugs in alcohol addiction have tiny benefits and are a distraction from the real challenges of limiting the availability and increasing the cost of alcohol. This bad medicine is all too familiar. Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. 1 2 3 4 5 6
7 8
Scottish Medicines Consortium. Nalmefene 18 mg film-coated tablets (Selincro®). 2013. www.scottishmedicines.org.uk/files/advice/nalmefene_Selincro_FINAL_September_2013_ website.pdf. National Institute for Health and Care Excellence. Single technology appraisal. Nalmefene for reducing alcohol consumption in people with alcohol dependence. 2014. www.nice. org.uk/nicemedia/live/14317/66222/66222.pdf. Gual A, ESENSE 2 Study Group. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol 2013;23:1432-42. Mann K, Bladström A, Torup L, Gual A, van den Brink W. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013;73:706-13. Safety and efficacy of nalmefene in patients with alcohol dependence (SENSE). http:// clinicaltrials.gov/ct2/show/results/NCT00811941?term=Sense+nalmefene&rank=1& sect=Xd8k96015#outcome8. Van den Brink W, Aubin HJ, Bladström A, Torup L, Gual A, Mann K. Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies. Alcohol Alcohol 2013;48:570-8. Boniface S, Shelton N. How is alcohol consumption affected if we account for under-reporting? A hypothetical scenario. Eur J Public Health 2013;23:1076-81. Nalmefene. British National Formulary. 2014. www.medicinescomplete.com/mc/bnf/current/ PHP33535-nalmefene.htm.
[email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g1531 doi: 10.1136/bmj.g1531 (Published 14 February 2014)
Page 2 of 2
VIEWS & REVIEWS
9
McAvoy BR. Naltrexone effective for alcohol dependence. Cochrane Primary Health Care Field 2010. www.cochraneprimarycare.org/pearls/naltrexone-effective-alcohol-dependence.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Cite this as: BMJ 2014;348:g1531 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
