Oral Methadone Maintenance Research Articles

What are the reasons for injected methadone use? A qualitative study of people who use drugs parenterally in Barcelona.

Oral methadone maintenance is a widely adopted and effective treatment for heroin and other opioid dependencies. However, injectable methadone usage may pose greater risks than heroin itself. Despite decades of oral methadone treatment in Spain, there is limited understanding of the motivations for parenteral consumption. This study aimed to examine the reasons for methadone injection, delineate its specific advantages and disadvantages compared with those of heroin use, and assess the benefits and drawbacks of supervised methadone injection within a harm reduction service from the perspective of people who inject drugs. A qualitative phenomenological study was conducted in 11 patients at a safe injection facility in Barcelona. Semistructured interviews revealed that the reasons for injecting methadone were its provision of a euphoric rush, the pleasurable sensation of needle insertion, and the avoidance of gastrointestinal discomfort associated with oral methadone use. The main attraction of methadone injection was its accessibility as a legal and fully state-funded treatment option in Spain, coupled with its effectiveness in relieving withdrawal symptoms. However, notable disadvantages included the risks inherent in injection. The benefits of supervised consumption rooms were its provision of immediate medical assistance in overdose situations, ease of access, and physical safety. Drawbacks included waiting times, limited opening hours, neighborhood stigmatization, and the distance people who inject methadone had to travel when obtaining methadone from the illicit market. Based on these findings, we make several recommendations aimed at reducing the harm associated with methadone injection and emphasize the need for comprehensive harm reduction strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Diacetylmorphine for Adults With Opioid Dependence


 Injectable diacetylmorphine might provide more benefits and lower costs compared with oral methadone maintenance therapy in patients with severe opioid use disorder.
 The Canadian Research Initiative in Substance Misuse guideline recommends that both injectable diacetylmorphine and hydromorphone should be considered as treatment options for individuals with severe, treatment-refractory opioid use disorder and ongoing illicit injection opioid use, and that the injectable opioid agonist treatment should have an end date to transition to an oral opioid agonist treatment.
 No recent studies on the clinical effectiveness of diacetylmorphine for injection in comparison with methadone or buprenorphine were identified.
 No cost-effectiveness studies of injectable diacetylmorphine compared with buprenorphine were identified.

Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction†.

Supervised injectable heroin (SIH) treatment has emerged over the past 15 years as an intensive treatment for entrenched heroin users who have not responded to standard treatments such as oral methadone maintenance treatment (MMT) or residential rehabilitation. To synthesise published findings for treatment with SIH for refractory heroin-dependence through systematic review and meta-analysis, and to examine the political and scientific response to these findings. Randomised controlled trials (RCTs) of SIH treatment were identified through database searching, and random effects pooled efficacy was estimated for SIH treatment. Methodological quality was assessed according to criteria set out by the Cochrane Collaboration. Six RCTs met the inclusion criteria for analysis. Across the trials, SIH treatment improved treatment outcome, i.e. greater reduction in the use of illicit 'street' heroin in patients receiving SIH treatment compared with control groups (most often receiving MMT). SIH is found to be an effective way of treating heroin dependence refractory to standard treatment. SIH may be less safe than MMT and therefore requires more clinical attention to manage greater safety issues. This intensive intervention is for a patient population previously considered unresponsive to treatment. Inclusion of this low-volume, high-intensity treatment can now improve the impact of comprehensive healthcare provision.

The relationship between sugar-containing methadone and dental caries: A systematic review

Objectives: To review the evidence of a relationship between sugar-containing methadone and dental caries. Data sources: A systematic search of Cochrane Library, PubMed, PsychINFO, EMBASE, MEDLINE, Current Controlled Trials, WHO, OHRN, SIGLE and ERIC databases was conducted from January 1978 up to June 2010. Study selection: Articles were assessed and data abstracted independently by two reviewers. Papers that provided information about methadone and dental caries and were written in English were included, regardless of type of publication, authors, source of financial support and outcomes. Nineteen articles were identified; of these only three contained quantitative evidence, one of which was a survey. Conclusions: Many people on oral methadone maintenance programmes have been reported to have high levels of dental caries. However, there is no strong evidence to support a direct link between sugar-containing methadone and an increase in dental caries. High quality studies are required to assess the potential adverse effects of methadone on oral health.

Supervised Injectable Heroin After Failure of Oral Methadone Maintenance

At least 5% to 10% of heroin addicts continue illicit opiate use despite treatment with oral methadone. In several randomized trials, supervised

Symptom complaints of patients prescribed either oral methadone or injectable heroin

Many methadone patients and untreated heroin users have an ambivalent attitude toward methadone maintenance. This may be a result of the widespread belief that methadone produces various side effects not found with heroin. This study compared the symptom complaints of patients on oral methadone maintenance (MMT) with those of patients prescribed injectable heroin (IHT). A convenience sample of 117 (63 MMT, 54 IHT) patients was recruited from two maintenance clinics. With the use of a self-completion questionnaire, patients were interviewed about a range of symptoms they had experienced and which, in their view, were due to maintenance substance immediately after the last 10 opioid administrations, during the previous week and previous year. The complaints of the two groups overlapped considerably with only few significant differences; these appeared related to the route of administration. IHT patients reported a larger number of complications experienced immediately after administration than MMT patients ( p = .007). From the patients' view, methadone does not produce many more or side effects very different from heroin and thus seems at least as tolerable as heroin for maintenance treatment.

Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction

Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence. In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index. The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients). Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)

Stereoselective Quantification of Methadone and a d6-labeled Isotopomer Using High Performance Liquid Chromatography-Atmospheric Pressure Chemical Ionization Mass-Spectrometry: Application to a Pharmacokinetic Study in a Methadone Maintained Subject

There is evidence that the apparent oral clearance of rac-methadone is induced during the early phase of methadone maintenance treatment. However, it is not known if this is due to changes in bioavailability or if this phenomenon is stereoselective. This knowledge can be obtained by administering a dose of stable-labeled methadone at selected times during ongoing treatment. Therefore, the authors developed a stereoselective high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry assay for the quantification of the enantiomers of methadone and a d(6)-labeled isotopomer. The compounds were quantified in a single assay after liquid-liquid extraction and stereoselective high performance liquid chromatograph with atmospheric pressure chemical ionization-mass spectrometry detection. The following ions were monitored: m/z 310.15 for unlabeled methadone; m/z 316.15 for methadone-d(6); and m/z 313.15 for the methadone-d(3) (internal standard). Calibration curves ranged from 0.5 to 75 ng/mL for each compound. Extraction recovery was approximately 80% for all analytes, without evidence of differences between the unlabeled and stable-labeled compounds or concentration dependency. Minor ion promotion was observed (<15%) but this was identical for all analytes including the d(3)-labeled internal standard, with peak area ratios in extracted samples identical to control injections. The isotopomers did not alter each others' ionisation, even at 10:1 concentration ratios, and 10-fold diluted samples were within 10% of the nominal concentration. Assay performance was acceptable, with interassay and intra-assay bias and precision <10% for all compounds, including the upper and lower limits of quantitation. In conclusion, the assay was successfully applied to quantify the concentration of the methadone enantiomers of both orally administered unlabeled methadone and an intravenous 5 mg dose of methadone-d(6) in a patient receiving chronic oral methadone maintenance therapy.

Opioid Addicts at Admission vs. Slow-Release Oral Morphine, Methadone, and Sublingual Buprenorphine Maintenance Treatment Participants

With use of a randomized study design, quality of life (QOL) and physical symptoms of opioid addicts at admission were compared with slow-release oral morphine, methadone, and sublingual buprenorphine maintenance program participants after 6 months of treatment. The study was conducted from February to July 2004 in the outpatient drug user treatment center at University Department of Psychiatry at Innsbruck, providing maintenance treatment programs and detoxification in Tyrol, Austria. One hundred twenty opioid users seeking treatment were compared with 120 opioid-dependent patients retained for 6 months on a slow-release oral morphine, methadone, or sublingual buprenorphine maintenance program. The German version (“Berlin Quality of Life Profile”) of the Lancashire Quality of Life Profile was used, and illicit opioid use was determined by urinalysis. Physical symptoms were measured by using the Opioid Withdrawal Scale. Urinalyses revealed a significantly lower consumption of cocaine and opioids in all three substitution groups than in patients at admission (p < 0.001 and p ≤ 0.004, respectively). Both the buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission for stomach cramps (p ≤ 0.002), muscular tension (p ≤ 0.027), general pain (p ≤ 0.001), feelings of coldness (p ≤ 0.000), heart pounding (p ≤ 0.008), runny eyes (p ≤ 0.047), and aggressions (p ≤ 0.009). Patients who received slow-release oral morphine treatment generally showed the least favorable QOL scores compared with patients at admission or sublingual buprenorphine and methadone clients. Patients in the sublingual buprenorphine or methadone program showed nearly the same QOL scores. The buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission regarding leisure time (p ≤ 0.019), finances (p ≤ 0.014), mental health (p ≤ 0.010), and overall satisfaction (p ≤ 0.010). Slow-release oral morphine is a well-established treatment for pain, but more research is required to evaluate it as a treatment for heroin dependence. The present data indicate that slow-release oral morphine could have some disadvantages compared with sublingual buprenorphine and methadone in QOL, physical symptoms, and additional consumption. The results further suggest that buprenorphine treatment is as effective as methadone in effects on quality of life and physical symptoms.

Increase of Oral Methadone Dose in Methadone Injecting Patients

A pilot study was initiated in seven methadone injecting patients to examine whether intravenous methadone use in patients in oral methadone maintenance treatment could be decreased by increased oral methadone dose. During the study, patients had a standardized methadone dose increase for three weeks, followed by a 12-week follow-up period. Mean methadone doses prior to, and at the end of the study, were 99 mg/day and 163 mg/day, respectively. On week 15, the mean frequency of injection and the mean proportion of methadone dose injected were reduced to 46% of the values measured at week 0 (p = 0.043 and p = 0.028, respectively). Two patients did not modify their frequency, nor their dose of injected methadone, four patients decreased their use of injectable methadone, while one completely stopped injecting methadone. Since the completion of the pilot study, an augmentation of oral methadone dose has been proposed as a therapeutic option to 18 other methadone injecting patients. Five patients did not change their frequency of injection. They did, however, either completely stop or decrease their illicit opiate consumption. Nine patients decreased their frequency of methadone injection from a mean 95 % down to 35 %. Finally, four patients completely stopped injecting methadone Although the present results have to be confirmed by controlled studies including a larger number of patients, when considering the high frequency of methadone injection in some places and the associated problems, the therapeutic option of increasing methadone dose should be considered further.

Medical Co-Prescription of Heroin to Chronic, Treatment-Resistant Methadone Patients in the Netherlands

This paper begins with a brief description of the epidemiology of heroin addiction in the Netherlands and an overview of the current treatment system, with special emphasis on oral methadone maintenance. It is followed by a short history of the debate over the prescription of heroin to addicted patients. This history reveals that alternatives to methadone have been viewed as essential in the Netherlands since the early 1980s. Earlier experiments with intravenous morphine, intravenous methadone and oral dextromoramide (PalfiumR) were not as successful as had been hoped and precluded their introduction in daily practice. Finally, recent experiences in Switzerland with the medical prescription of heroin facilitated the decision to initiate a scientific study of the medical co-prescription of heroin in the Netherlands. The paper provides a detailed description of the randomized clinical trial regarding the effectiveness of co-prescribed heroin that is now underway in the Netherlands. It concludes with a brief discussion of the likely consequences for future treatment options of different study outcomes.

Oral and intravenous methadone use: some clinical and pharmacokinetic aspects

A sample of 15 patients participating in an injectable methadone trial and of 15 patients in an oral methadone maintenance treatment, who admitted injecting part or all of their methadone take-home doses, were compared to 20 patients in maintenance treatment who use methadone exclusively by mouth. The present study confirms the poorer general health, the higher levels of emotional, psychological or psychiatric problems, the higher use of illicit drugs, and the higher number of problems related to employment and support associated with the use of the intravenous mode of administration of methadone. As expected, due to the shunt of metabolism in the gut wall and of the liver first-pass effect, higher concentration to dose ratios of ( R)-methadone, which is the active enantiomer, were measured in the intravenous group (23% increase). This difference reached an almost statistically significant value ( P=0.054). This raises the question whether the effect of a higher methadone dose could be unconsciously sought by some of the intravenous methadone users.

Heroin Prescribing in the British System: Historical Review

Heroin has been prescribed in the UK in the treatment of addiction for nearly a century. However, despite international fascination with this practice, it is only rarely employed by doctors in the UK – to less than 2% of addicts in treatment in the mid-1990s. The history of changing professional attitudes to, and use of, heroin prescribing over the 20th century is described. Particular attention is paid to the period since the mid-1960s when a new modern-day drug problem emerged with young disenfranchised heroin injectors appearing in Britain for the first time, and to the post-HIV debate with its wide public health consideration, the urgent need to reduce needle-sharing and the accumulating evidence of multiple benefits from oral methadone maintenance programmes. New data on the extent of heroin prescribing in the UK in the mid-1990s are summarised.

Fortnightly Review: Methadone maintenance treatment in opiate dependence: a review

This paper examines the changes and advances in research and clinical practice and examines the role of treatment structure and programme characteristics in the delivery of methadone maintenance. Methadone prescribing has become much more available over the past decade, both in countries with a history of its use, such as the United Kingdom and Australia, and in countries around the world which previously had not endorsed substitute prescribing.1 There is a need to examine closely the framework in which this treatment is delivered to ensure that the modes of delivery most effective from both cost and benefit perspectives are utilised. This review focuses entirely on methadone maintenance because this is the most extensively evaluated and most used treatment, with about a quarter of a million drug misusers receiving methadone treatment globally. A small number of experimental diamorphine and buprenorphine substitute programmes are being evaluated in several countries. Most studies have come from the United States and focus on the long term use of methadone in a specific setting; in contrast, methadone treatment in the United Kingdom has received virtually no formal evaluation to date bar one study.2 There is concern that a considerable amount of the methadone prescribing could be having little impact on illicit drug use or risk taking behaviour,3 a recent study of drug users in police custody echoes this.4 The Advisory Council on the Misuse of Drugs has recommended a shift to a more structured approach for delivery of oral methadone maintenance. The organisation and regulation of methadone maintenance treatment varies widely, with explicit guidelines for programme operation in the United States and Australia and a virtual absence of structure and regulation in Britain. It is likely that policy analysts and treatment providers in countries with high levels of regulation and structured programmes …

Fatal Methadone Poisoning in Children: Report of Four Cases

Abstract During the past two years, the Brooklyn office of the Office of the Chief Medical Examiner of New York City has encountered four deaths in children due to methadone poisoning. In all cases, prepared methadone drinks or methadone hydrochloride tablets were carelessly left around the house within the reach of children by either parents or friends of the family who were on a methadone maintenance program. The increasing use of this oral methadone maintenance technique in the management of heroin addicts has made this drug more accessible, thereby increasing the danger of accidental ingestion by children. It is to be expected that with even wider adoption of this program, that accidental methadone poisoning in children will become more common. Four deaths in children due to methadone poisoning are presented in this communication.

Oral Methadone Maintenance

To the Editor.— I would like to respond to the letter "Oral Methadone Maintenance" by Dr. G. James Berry, which appeared in a recent issue ofThe Journal(220:1617, 1972). Over the past 2 1/2 years we have been involved in observing patients maintained with methadone hydrochloride in a clinic for this purpose. Although it is certainly true that a certain percentage of patients can and will be maintained with dosages as low as 30 mg/day (we have one who is taking 10 mg/day), we do not feel that the implication that most can be maintained with anything like this low dosage should gain credence. Many factors influence dosage, such as psychological situations, habits of previous abuse, fears concerning proper maintenance dosage, variations in perspiration rates, kinds of work, and intercurrent emotional states. In our observation, most of these patients require between 60 and 90 mg of methadone hydrochloride, with

Oral methadone maintenance.

To the Editor.— With one exception, I concur with the position taken by the AMA Council on Mental Health in their explication, Oral Methadone Maintenance Techniques in the Management of Morphine—Type Dependence. That position perpetuates the impression that, in general, addicts must be maintained at a daily dose level of between 80 and 120 mg. And, occasionally, a daily dose as high as 160 mg and above is required to attain the intended effect. Double-blind studies done in our clinic, and a similar study by Goldstein, demonstrate that most addicts can be successfully maintained with much smaller doses—as low as 30 mg/day. We were unable to demonstrate a significant difference in the behavior of groups of patients maintained continuously with 30, 50, and 100 mg of methadone hydrochloride daily when compared with retention in the program, attendance, employment, illegal activities, and involvement with their families. The one exception was a

Oral methadone maintenance techniques in the management of morphine-type dependence

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