Methadone for opioid detoxification as effective as other medications, but all have high relapse rates

Heroin addiction

Dependence on opiates (a group of drugs including heroin, morphine, and methadone) can be highly destructive for both the individual and for the people around them. Heroin addiction in particular is associated with major health risks, co-morbid mental health problems, and a wide-range of social issues. Attempting to stop opiate use leads to severe withdrawal symptoms (including nausea and vomiting, muscle pain, and negative affect such as feelings of anxiety and irritability) as well as intense drug cravings and disturbed sleep that may last for many months.

Detoxification programmes are recommended by NICE for people who wish to stop using opiates. The aim is to minimise withdrawal symptoms, which may then help people to remain abstinent. Medication, such as methadone, is prescribed at steadily reducing amounts (“tapered” doses) over the defined time course of the detox programme. To find out more about detoxification treatment have a look at this PDF quick reference guide on the NICE website.

The Cochrane Collaboration recently updated their systematic review of trials assessing the use of methadone for opiate detoxification compared to placebo and to any other pharmacological detoxification treatment. They included trials assessing detox from heroin, methadone and buprenorphine.


The primary outcomes of interest were:

  1. Completion of treatment: number of participants completing the detoxification programme
  2. Acceptability of the treatment:
    1. Duration and severity of signs and symptoms of withdrawal, including patient self-rating
    2. Side effects
  3. Results at follow-up:
    1. Number of participants abstinent at follow-up
    2. Naloxone challenge (naltrexone treatment blocks the effects of opiates and is sometimes used by people who have completed detox to help them remain abstinent; read more about this on the NICE website).

The secondary outcomes of interest were:

  1. Use of primary substance of abuse:
    1. Number of participants who referred to the use of opiate during the treatment
    2. Number of participants with urine samples positive for opiate


The authors identified 23 studies (2467 participants; across 8 countries) for inclusion in a qualitative summary of results, and 17 studies for meta-analysis. Treatment duration varied from three to 30 days, with 18 inpatient and 5 outpatient programmes.

Main findings

There was no difference in completion of detoxification treatment for methadone compared to all other pharmacological treatments

There was no difference in completion of detoxification treatment for methadone compared to all other pharmacological treatments

  • Tapered methadone programmes versus all other pharmacological detoxification treatments:
    • Completion of treatment. Sixteen studies (1381 participants). There was no difference in the number of participants completing methadone programmes (59%) compared to all other treatment programmes (54%; RR = 1.08; 95% CI: 0.97, 1.21)
    • Acceptability of treatment. Withdrawal symptoms and side effects reported by each study are reported in a series of tables, but variation in reporting across studies prevented any direct comparisons
    • Abstinence at follow-up. Three studies (386 participants), with a mean follow-up of 1.5 months. There was no difference in number abstinent at follow-up in the methadone groups (24%) compared to all other treatment groups (26%; RR = 0.98; 95% CI: 0.70, 1.37)
    • Naloxone challenge. One study (66 participants). More participants in a clonidine treatment group than the methadone group continued naloxone treatment (RR 0.50; 95% CI 0.26, 0.95)
    • Use of primary substance during treatment. Three studies reported this, but only total number of positive urine tests per group were reported, with no information related to the number of participants these results related to.
  • Tapered methadone compared to placebo medication:
    • Two studies compared methadone to placebo (38 participants). More participants completed the methadone treatment programme compared to the placebo (RR = 1.95; 95% CI: 1.21, 3.13). However one study assessed detox from buprenorphine, and the other study from heroin. There was a large advantage of methadone compared to placebo for completion in the heroin group (RR = 3.33; 95% CI: 1.25, 8.91), but there was no difference in completion between placebo and methadone in the buprenorphine group.


The authors conclude:

The results indicate that tapered methadone and the other substances used in the included studies are effective in the treatment of heroin withdrawal syndrome, although symptoms presented by participants differed according to the drug used… Nevertheless, a majority of patients relapsed in heroin use, and relapse from the drug-free state to re-addiction is the main problem in heroin addiction.


Opiate addiction is a chronic and relapsing condition, and the majority of patients relapsed

Opiate addiction is a chronic and relapsing condition, but even brief periods of abstinence may be beneficial

The conclusions of this review were limited by variation in outcome measures across studies. High rates of relapse do make it difficult to define what constitutes success in detox programmes, and completion of treatment is often used as the main indicator. However to give a better clinical picture of whether programmes are succeeding in reducing opiate use, future trials need to better assess substance use during treatment and abstinence at follow-up.

Programmes included also varied considerably in duration (from 3 to 30 days), dosage programme, and clinical setting (inpatient versus outpatient), again limiting clinically relevant conclusions. The authors also combined trials assessing detox from heroin with those assessing detox from methadone and buprenorphine. Since heroin use is associated with greater harms and a more unstable lifestyle than methadone and buprenorphine, treatment success and withdrawal severity may vary accordingly.

Overall this review demonstrates that despite high relapse rates, pharmacological detoxification programmes can be effective, and that there is so far no evidence to suggest methadone is more effective than other medications. While there is certainly debate about whether detox programmes are useful, the authors argue that the harms associated with heroin use are so high that even the brief periods of abstinence achieved through detox treatments are beneficial.  Indeed while NICE recommends detox programmes are offered to people who wish to become abstinent, they highlight that this should be accompanied by continued support, such as psychosocial therapy to address co-morbid mental health problems.


Amato L, Davoli M, Minozzi S, Ferroni E, Ali R, Ferri M. Methadone at tapered doses for the management of opioid withdrawal. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD003409. DOI: 10.1002/14651858.CD003409.pub4.

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Claire Mokrysz

Claire Mokrysz

Claire is a PhD student in the field of Mental Health at University College London. She holds a degree in Psychology and a Masters degree in Neuropsychology. Her research interests are broad across the field of mental health, with a particular focus on addiction and substance misuse. Through her research Claire hopes to contribute to better therapeutic options for people with substance dependence problems. Claire has also worked as a support worker in brain injury rehabilitation services and in supported living services for adults with learning difficulties.

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