Fw: Methadone comparison with buprenorphine (pure) from Norway.

Preston Peet ptpeet at NYC.RR.COM
Wed Mar 1 06:54:11 EST 2006

----- Original Message ----- 
From: Andrew Byrne 
To: ajbyrne at ozemail.com.au 
Sent: Tuesday, February 28, 2006 6:01 PM
Subject: Methadone comparison with buprenorphine (pure) from Norway.

A randomised clinical trial of methadone vs. buprenorphine to opioid dependants. Kristensen O, Espegren O, Asland R, Jakobsen E, Lie O, Seiler S. Tidsskr Nor Laegeforen 2005 125;2:148-151  


Dear Colleagues, 

After decades of denial in Norway, methadone was finally introduced in 1998 and buprenorphine in 2000 for opioid dependence.  These researchers set out to compare the effects of the two maintenance therapies in their own drug using population.  


There were 50 long term (>10 years) opioid dependent subjects randomised to receive 16mg fixed dose buprenorphine or variable dose methadone (mean daily dose 106mg, range 80-160mg) over 6 months observation.  Patient retention rate was 85% in the methadone group and 36% for those prescribed buprenorphine.  Opiate positive urine tests were slightly lower in the methadone group (20% vs. 24%).  Importantly, the methadone subjects reported less high risk behaviour.  For some reason, only the buprenorphine group (or the minority who remained in the trial) reported significant improvements in general health.  


This small study should be the last to compare methadone and buprenorphine in this way.  Their results were predictable, adding little more than Scandinavian corroboration to 20 years of preceding research.  The fixed dose buprenorphine dosing schedule here was probably based on a successful Swedish model (Kakko, 2003).  However, methadone and buprenorphine should both be prescribed in tailored doses according to clinical need, using appropriate increments (eg 5mg for methadone, 0.4mg for buprenorphine).  It is likely that some buprenorphine patients in this trial dropped out because they received too little or too much of the drug (32mg is the maximum recommended dose).  I could only access this abstract in English translation, so I am not able to bring further details at this point.  


There is no longer any doubt that both methadone and buprenorphine are effective for substantial numbers of heroin addicted subjects treated with adequate supervised (and flexible) doses along with psychosocial supports.  


>From a body of research, including numerous RCT's, we know that when compared to buprenorphine: (1) methadone generally suits a higher proportion of the total and (2) it reduces the use of other opiates to a greater degree and (3) whilst in treatment, such patients are less likely to be involved in high risk behaviours.  Methadone is also considered to be safe in pregnancy and is much cheaper and easier to administer.  Thus methadone should probably still be our preferred first option and buprenorphine kept in reserve for particular indications.  If there are concerns about patients misusing methadone then take-away doses should be limited until stability has been demonstrated.  It may be that long-term users are less likely to fare well on buprenorphine, as shown in this study.  


It is unfortunate that decisions for physicians and especially for patients are frequently dictated not by clinical considerations as much as by regulatory constraints.  In some countries (and for no logical reason) these are far more onerous and odious for methadone, while others artificially restrict or even ban the use of buprenorphine for addiction treatment, despite almost 20 years of favourable research.   


My feeling is that buprenorphine should be available as an option to all patients who report problems taking methadone.  Such patients, however, should be carefully monitored since a high proportion relapse (in this case 74% within 6 months) and may need to transfer back to methadone or to consider other alternatives such as detoxification.  


There is no indication that new combination formulation of buprenorphine (with naloxone) will be any more effective than the pure product.  Some evidence points towards lowered efficacy (50% higher doses were required in one small comparative trial).  While some have stated that sublingual naloxone is not relevant clinically, others have found objective changes and significant absorption (10% or more).  Naloxone has a rapid serum clearance time (~5 minute half life) but its serum half life following distribution is just over one hour.  While one hopes for less diversion with this formulation, Charles (Bob) Schuster writes: "It is unlikely, however, that any formulation can be developed that cannot be altered by 'street chemists' into a more abusable form." 


Comments by Andrew Byrne .. 




Harris DS, Jones RT,  Welm S, Upton RA, Lin E, Mendelson J. Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine. 2000 Drug and Alcohol Dependence 61:85-94


Berkowitz BA. The relationship of pharmacokinetic to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet. 1976 1;3:219-30


Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-associated relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. (2003) Lancet 361:662-668


Schuster CR. History and current perspectives on the use of drug formulations to decrease the abuse of prescription drugs. Drug and Alcohol Dependence (2006 in press, pre-publication version, accessed 28/2/06) 



   Dr Andrew Byrne MB BS (Syd) FAChAM (RACP)

   Dependency Medicine,

   75 Redfern Street, Redfern,

   New South Wales, 2016, Australia

   Email - ajbyrneATozemail.com.au

   Tel (61 - 2) 9319 5524  Fax 9318 0631


Thomas De Quincey's Confessions book on free web site: 


My grandfather Harry Gracie's letters from 1924 trip to Mayo Clinic:


Author of: "Addict in the Family" and

"Methadone in the Treatment of Narcotic Addiction"




AATOD Dole-Nyswander Award nominee, Atlanta 2006. 


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