The Facts About Methadone


The treatment of opioid addiction (heroin or prescription pain pills) with methadone still has an unwarranted stigma attached to it.  I wanted to devote at least one blog entry to a summary of the most well-known studies that support this evidence-based treatment. When people speak against methadone, they usually say they don’t “believe” in it, without being able to give any scientific basis for their stance. 

Well, this is why I do “believe” in it. It’s not opinion. It’s science.

 Amato L, Davoli, et. al., An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment 2005; 28 (4):321-329. In this overview of meta-analyses and other reviews, they conclude that methadone maintenance is more effective in the treatment of opioid addiction than methadone detoxification, buprenorphine, or no treatment. Higher doses of methadone are more effective than low or medium doses. 

Bale et. al., 1980; 37(2):179-193. “Therapeutic Communities vs Methadone Maintenance” Archives of General Psychiatry Opioid-addicted veterans who presented to the hospital for treatment were assigned to either inpatient detoxification alone, admission to a therapeutic community, or to methadone maintenance. One year later, patients assigned to therapeutic communities or methadone maintenance did significantly better than patients whose only treatment was detoxification. Patients in these two groups were significantly more likely to be employed, less likely to be in jail, and less likely to be using heroin, than the patients who got only detox admission. Patients in the therapeutic communities needed to stay at least seven weeks to obtain benefit equal to patients assigned to methadone maintenance. 

Ball JC, Ross A., The Effectiveness of Methadone Maintenance Treatment. New York, NY: Springer-Verlag Inc., 1991. This landmark study observed six hundred and thirty-three male patients enrolled in six methadone maintenance programs. Patients reduced their use of illicit opioids 71% from pre-admission levels, with the best results (no heroin use) seen in patients on doses higher than 70 milligrams. Longer duration of treatment with methadone showed the greatest reductions in heroin use. Of patients who left methadone maintenance treatment, 82% relapsed back to intravenous heroin use within one year. This study also found a dramatic drop in criminal activity for addicts in methadone treatment. Within one year, the number of days involved in criminal activity dropped an average of 91% for addicts maintained on methadone. This study showed that methadone clinics vary a great deal in their effectiveness. The most effective clinics had adequate dosing, well-trained and experienced staff with little turnover, combined medical, counseling and administrative services, and a close and consistent relationship between patients and staff.

 Caplehorn JRM, Bell J. Methadone dosage and retention of patients in maintenance treatment. The Medical Journal of Australia 1991;154:195-199. Authors of this study concluded that higher doses of methadone (80 milligrams per day and above) were significantly more likely to retain patients in treatment.

 Caplehorn JR, Dalton MS, et. al., Methadone maintenance and addicts’ risk of fatal heroin overdose. Substance Use and Misuse, 1996 Jan, 31(2):177-196. In this study of heroin addicts, the addicts in methadone treatment were one-quarter as likely to die by heroin overdose or suicide. This study followed two hundred and ninety-six methadone heroin addicts for more than fifteen years. 

Cheser G, Lemon J, Gomel M, Murphy G; Are the driving-related skills of clients in a methadone program affected by methadone? National Drug and Alcohol Research Centre, University of New South Wales, 30 Goodhope St., Paddington NSW 2010, Australia. This study compared results of skill performance tests and concluded that methadone clients aren’t impaired in their ability to perform complex tasks.

 Clausen T, Waal H, Thoresen M, Gossop M; Mortality among opiate users: opioid maintenance therapy, age and causes of death. Addiction 2009; 104(8) 1356-62. This study looked at the causes of death for opioid addicts admitted to opioid maintenance therapy in Norway from 1997-2003. The authors found high rates of overdose deaths both prior to admission and after leaving treatment. Older patients retained in treatment died from medical reasons, other than overdose.

 Condelli, Dunteman, 1993: examined data from TOPS, the Treatment Outcome Prospective Study, assessed patients entering treatment programs from 1979 – 1981 and found data on improvement similar to DARP; longer duration of treatment in methadone maintenance shows lower use of illicit opioids. 

Dole VP, Nyswander ME, Kreek, MJ, Narcotic Blockade. Archives of Internal Medicine, 1966; 118:304-309. Consisted of thirty-two patients, with half randomized to methadone and the other half to a no-treatment waiting list. The methadone group had much higher rates of abstention from heroin, much lower rates of incarceration, and higher rates of employment.

 Faggiano F, Vigna-Taglianti F, Versino E, Lemma P, Cochrane Database Review, 2003 (3) Art. No. 002208. This review article was based on a literature review of randomized controlled trials and controlled prospective studies that evaluated the efficacy of methadone at different doses. The authors concluded that methadone doses of 60 – 100mg per day were more effective than lower doses at prevention of illicit heroin and cocaine use during treatment.

 Goldstein A, Herrera J, Heroin addicts and methadone treatment in Albuquerque: a year follow-up. Drug and Alcohol Dependence 1995 Dec; 40 (2): p. 139-150. A group of heroin addicts were followed over twenty years. One-third died within that time, and of the survivors, 48% were on a methadone maintenance program. The author concluded that heroin addiction is a chronic disease with a high fatality rate, and methadone maintenance offered a significant benefit.

 Gordon NB, Appel PW., Functional potential of the methadone-maintained person. Alcohol, Drugs and Driving 1995; 11:1: p. 31-37. This is a literature review of studies examining performance and reaction time of patients maintained on methadone, and confirms that these patients don’t differ from age-matched controls in driving ability and functional capacity.

 Gowing L, Farrell M, Bornemann R, Sullivan LE, Ali R., Substitution treatment of injecting opioid users for prevention of HIV infection. The Cochrane Database of Systematic Reviews, 2008, Issue 2, Ar. No. CD004145. Authors reviewed twenty eight studies, concluded that they show patients on methadone maintenance have significant reductions in behaviors that place them at risk for HIV infection.

 Gronbladh L, Ohlund LS, Gunne LM, Mortality in heroin addiction: Impact of methadone treatment, Acta Psychiatrica Scandinavica Volume 82 (3) p. 223-227. Treatment of heroin addicts with methadone maintenance resulted in a significant drop in mortality, compared to untreated heroin addicts. Untreated addicts had a death rate 63 times expected for their age and gender; heroin addicts maintained on methadone had a death rate of 8 times expected, and most of that mortality was from diseases acquired prior to treatment with methadone. 

Gunne and Gronbladh, 1981: The Swedish Methadone Maintenance Program: A Controlled Study, Drug and Alcohol Dependence, 1981; 7: p. 249 – 256. This study conducted a randomized controlled trial on inpatient opioid addicts to methadone maintenance with intensive vocational rehabilitation counseling, or a control group that were referred to drug-free treatment.  Over 20 years, this study consistently showed significantly higher rates of subjects free from illicit opioids, higher rates of employment, and lower mortality in the group maintained on methadone than the control group.

 Hartel D, Selwyn PA, Schoenbaum EE, Methadone maintenance treatment and reduced risk of AIDS and AIDS-specific mortality in intravenous drug users. Abstract number 8546, Fourth Annual Conference on AIDS, Stockholm, Sweden, June 1988. This was a study of 2400 opioid addicts followed over fifteen years. Opioid addicts maintained on methadone at a dose of greater than 60mg showed longer retention in treatment, less use of heroin and other drugs, and lower rates of HIV infection. 

Hubbard RL, Marsden ME,, Drug Abuse Treatment: A National Study of Effectiveness. Chapel Hill: University of North Carolina Press, 1989. Shows decreased use of illicit drugs (other than opioids) while in methadone treatment, and increased again after discharge.

 Kosten TR, Rounsaville BJ, and Kleber HD. Multidimensionality and prediction of treatment outcome in opioid addicts: a 2.5-year follow-up. Comprehensive Psychiatry 1987;28:3-13. Addicts followed over two and a half years showed that methadone maintenance resulted in significant improvements in medical, legal, social, and employment problems.

 Lenne MG, Dietze P, Rumbold GR, The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol on simulated driving. Drug Alcohol Dependence 2003; 72(3):271-278. This study found driving reaction times of patients on methadone and buprenorphine don’t differ significantly from non-medicated drivers; however, adding even a small amount of alcohol (.05%) did cause impairment.

 Marsch LA. The efficacy of methadone maintenance in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis Addiction 1998; 93: pp. 515-532. This meta-analysis of studies of methadone concludes that methadone treatment reduces crime, reduces heroin use, and improves treatment retention.

 Mattick RP, Breen C, Kimber J, et. al.,Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. The Cochrane Database of Systematic Reviews,  2003; (2): CD002209. This is a meta-analysis of studies of methadone treatment. The authors concluded that treatment of opioid dependence with methadone maintenance is significantly more effective than non-pharmacologic therapies. Patients on methadone maintenance are more likely to be retained in treatment and less likely to be using heroin. This study did not find a reduction in crime between the two groups. 

Metzger DS, Woody GE, McLellan AT, et. al. Human immunodeficiency virus seroconversion amoung intravenous drug users in- and out- of- treatment: an 18-month prospective follow up. Journal of Acquired Immune Deficiency Syndrome 1993;6:1049-1056. Patients not enrolled in methadone maintenance treatment converted to HIV positivity at a rate of 22%, versus a rate of 3.5% of patients in methadone maintenance treatment.

 Powers KI, Anglin MD. Cumulative versus stabilizing effects of methadone maintenance. Evaluation Review 1993: Heroin addicts admitted to methadone maintenance programs showed a reduction in illicit drug use, arrests, and criminal behavior, including drug dealing. They showed increases in employment. Addicts who relapsed showed fewer improvements in these areas. 

Scherbaum N, Specka M,, Does maintenance treatment reduce the mortality rate of opioid addicts? Fortschr Neurol Psychiatr, 2002, 70(9):455-461. Opioid addicts in continuous treatment with methadone had a much lower mortality rate (1.6% per year) than opioid addicts who left treatment (8.1% per year).

 Sees KL, Delucchi KL, “Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence” Journal of the American Medical Association, 2000, 283:1303-1310. Compared the outcomes of opioid addicted patients randomized to methadone maintenance or to180-day detoxification using methadone, with extra psychosocial counseling. Results showed better outcomes in patients on maintenance. Patients on methadone maintenance showed greater retention in treatment and less heroin use than the patients on the 180 day taper. There were no differences between the groups in family functioning or employment, but maintenance patients had lower severity legal problems than the patients on taper.

 Sells SB, Simpson DD (eds). The Effectiveness of Drug Abuse Treatment. Cambridge, MA: Ballinger, 1976: This was an analysis of information from DARP, the Drug Abuse Reporting Program, which followed patients entering three types of treatment from 1969 to 1972 and showed that methadone maintenance was effective at reducing illicit drug use and criminal activity. This study also demonstrated that addicts showed more improvement the longer they were in treatment. 

Strain EC, Bigelow GE, Liesbon IA, et. al. Moderate- vs high –dose methadone in the treatment of opioid dependence. A randomized trial. Journal of the American Medical Association 1999; 281: pp. 1000-1005. This study showed that methadone maintenance reduced illicit opioid use, and more of a reduction was seen with the addition of psychosocial counseling. Methadone doses of 80mg to 100mg were more effective than doses of 50mg at reducing illicit opioid use and improving treatment retention. 

Stine, Kosten; Medscape Psychiatric and Mental Health eJournal: article reminds us that though it’s clear that better outcomes for methadone patients are seen with higher doses (more than 80mg), many opioid treatment programs still underdose their patients.

 Zanis D, Woody G; One-year mortality rates following methadone treatment discharge. Drug and Alcohol Dependence, 1998: vol.52 (3) 257-260. Five hundred and seven patients in a methadone maintenance program were followed for one year. In that time, 110 patients were discharged and were not in treatment anywhere. Of these patients, 8.2% were dead, mostly from heroin overdose. Of the patients retained in treatment, only 1% died. The authors conclude that even if patients enrolled in methadone maintenance treatment have a less-than-desired response to treatment, given the high death rate for heroin addicts not in treatment, these addicts should not be kicked out of the methadone clinic.

 Do these studies mean that methadone works for every opioid addict? I don’t think so. Every medication has side effects and dangers. Methadone is no different. For a variety of reasons, methadone may not work for some addicts.  But this treatment has helped many addicts. At the very least, it can keep them alive until a better treatment comes along.


5 responses to this post.

  1. I am anesthesiologist. Dr.Vorobiev Drug Clinic. Belgrade. Agree with the author that under proper medical supervision, under strictly following the rules of treatment, with full patient”s cooperation and understanding the tasks of the treatment Methadone program works not bad. The problem is that in practice the most patients and many clinics dont adhere to rules of treatment. This attitude combined with side effects of Methadone and consequences of long- term use of Methadone discredits the method. To my opinion there is no an absolute treatment for opioid addiction. Subutex, Suboxone, Rapid detox with following Naltrexone program is a good alternative. And for a lot of patients it works well. At our clinic we do over 200 rapid detox procedures a year. Comfortable treatment. Reliable results. We use Naltrexone (Vivitrol) implant program to secure results of detoxification.


    • Hmmm…yes, as I replied to you on, most reputable treamtent centers in the U.S. stopped doing rapid detox due to the expense and increased complication rate.
      I do agree that using naltrexone depot injections or implants may change success rates. The depot injection just got approved in the U.S. at the end of last year. For more on this, see my latest post.
      I also agree that there’s no one best treatment for every addict. We need to take advantage of all evidence-supported treatment for opioid addiction, and naloxone and naltrexone definitely have a place in the toolkit, hopefully a bigger place with the longer acting preparations.


  2. Posted by lil red on July 17, 2011 at 12:49 pm

    Thank you so very much for your educated, informative posts regarding the efficacy of MMT. As a new patient who has seen vast improvement due to MMT, I greatly appreciate these posts as I am constantly scouring the net for info about this treatment. I am however greatly concerned by the backlash against MMT. There seems to be a quite large portion of people, some even Dr.s and treatment professionals, who abhor MMT and will often ignore or refuse to acknowledge all the literature illustrating the efficacy of MMT. Almost all prisons and parole/probation refuse to even allow stabalized MMT patients to continue. These “professionals” many whom are our polititians, law-makers, policy makers and law enforcement officers, refuse to see MMT as anything but “junk science” that promotes drug abuse by “substituting” methadone for heroin, ect and that the ONLY effective treatment is abstinance only, the AA NA way. As someone who has been failed and victimized by abstinence only treatments, I find this appaling and frightening. As someone who also totally believes in the ED- endorphin deficiency theory, I may need access to MMT for life and thus I live in fear that MMT may be taken away from us by one of these politicians who believe abstenance only programs to be the ONLY viable treatment for opioid addiction.

    Do you believe in the theory of ED, endorphin defeciency? I’d truly love to hear your opinion. Also, do you think there is a possibility that we could see the end of MMT due to this ignorance and prejudice? Thank you so much again for your wonderful posts and blog, it is truly a great asset and so very helpful!


    • Thank you, and thanks for writing.

      I don’t think MMT is going anywhere. It’s been around for 45 years, and it’s the most evidence-based treatment in all of medicine. Many politicians, in a misguided attempt to curry favor with voters, have spoken out against MMT and tried to outlaw it. Then some well-respected and knowledgable doctors have to educate this politician, and many times he changes his mind. One example is Rudy Guliani. I think at one time he said something about wanting to close opioid treatment programs. Once he was educated by some top docs, he changed his mind and has been supportive of them. It’s hard to argue with the top docs at NIH, CSAT, SAMHSA, and CDC.

      We can’t – yet – measure endorphins. When we can, I think we will have objective evidence of the biological changes that occur when opioids are ingested long term. There’s so much exciting brain science being done right now, not only with opioids and opioid receptors, but also cannabinoid receptors and endocannabinoids.

      We know that as a result of using drugs, and I’m not just talking opioids here, the structure of the brain undergoes physical changes. It may be a change in the way opioid receptors react, rather than the amount of endorphins, that gives those months of post-acute withdrawal in patients who have used opioids long-term. Either way, it’s a change in the structure or function of the brain.

      Don’t get me started about the law enforcement and judicial systems. In my neck of the woods, these organizations are…. backwards. That’s putting it nicely. Apparently they don’t keep up to date with results in their own field, at the successful treatment programs in large cities, like the Riker’s Island KEEP program. I hate to say it, but it may take some civil lawsuits to change these systems. I’ve been directing patients who were “sentenced” to stop their methadone to contact the ACLU or other organizations. These judges and law enforcement officers don’t seem to realize they are practicing medicine without a license. I believe they would be liable if the patient had a bad outcome, whether that’s a relapse or, heaven forbid, death. Other states have had successful suits and it’s changed the way some jails operate.

      It’s so sad when people in positions of power make up their minds about something without knowing anything about it. It speaks volumes about their character. I take it as a lesson to always remain teachable, and open to new information, based on good science of course.


  3. I think that people sick who wants to be free of illegal drugs should have the right to do so , pain and misery free!


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