Tag Archive: MMT.

Drug addicts should completely end their addictions rather than just cut their use, the government’s new strategy states.

Ministers said their „drugs-free recovery“ policy would include former addicts mentoring current ones.

The plans could see addicts lose benefits if they do not co-operate.

The former Labour government’s strategy was to reduce the harm caused by drugs by initially stabilising addictions, rather than trying to end them.

Parts of the strategy will apply to the whole of the UK, but in England ministers want to set up a network of former addicts to help drug users overcome their dependency.

Under the Home Office plans, treatment and rehabilitation centres would fall under the control of local partnerships which would target the specific needs of communities.

The strategy outlines the setting up of „Community Recovery Champions“ networks where people who have recovered from drug dependency could mentor others who seek their help.

Ministers said they will also target the supply of drugs in the UK, with a renewed focus on seizing the assets of those involved in the drugs trade, both at home and abroad.

‚Legal highs‘

Prescription-based treatments, such as the heroin-substitute methadone will continue, but it is not yet clear how much funding will be allocated.

Ministers also want to link drug treatment with welfare benefits in England, Wales and Scotland.

They launched a consultation paper in August that suggested a „financial benefit sanction“ if addicts did not take action to address their substance dependency.

Powers to temporarily ban ‚legal highs‘ until they are proven to be medically safe will come into effect immediately.

But Oscar Dagnone, medical director at CRI, an organisation that works with drug addicts, warned against trying to implement a „one-size fits all“ anti-drugs policy.

„We have to focus on the individual. Everyone is different,“ he said.

„I have never seen a drugs problem. I have seen people with problems and using drugs to deal with their problems. The issue we have in the UK is we have just been focussing on what we see as ‚problematic drug users‘. Everyone is in a different situation.“



PORTO, Portugal—This country’s move to decriminalize illicit substances—Europe’s most liberal drug legislation—turns 10 years old this month amid new scrutiny and plaudits.

Portugal’s decriminalization regime has caught the eye of regulators in Europe and beyond since it was implemented in 2001. Proponents credit the program for stanching one of Europe’s worst drug epidemics. Critics associate it with higher crime and murder rates. Approaching a decade in force, it is providing a real-world model of one way to address an issue that is a social and economic drag on countries world-wide.

Norway’s government formed a committee to look at better strategies for dealing with drug abuse and sent two delegates to Portugal in early May. Danish politicians have also talked of moving toward full decriminalization. In March, Danish parliamentarian Mette Frederiksen of the opposition Social Democrats praised the Portuguese model.

„For us, this is about the addicts leading a more dignified life,“ she told Danish daily Berlingske. „We want to lower the death rates, the secondary symptoms and the criminality, so we look keenly to Portugal.“

Markel Redondo for The Wall Street JournalA patient takes her methadone dose at a Porto rebab center that is part of Portugal’s decadelong experiment with drug decriminalization.



Decriminalization has been criticized by United Nations bodies. In its 2009 annual report, the International Narcotics Control Board expressed „concern“ over approaches that decriminalize drugs or introduce alternative treatments. „The movement poses a threat to the coherence and effectiveness of the international drug-control system and sends the wrong message to the general public,“ the board wrote.

In July 2000, Portugal moved beyond previous liberalization regimes in places like the Netherlands by passing a law that transformed drug possession from a matter for the courts to one of public and community health. Trafficking remained a criminal offense but the government did away with arrests, courts and jail time for people carrying a personal supply of anything from marijuana to cocaine to heroin. It established a commission to encourage casual users to quit and backed 78 treatment centers where addicts could seek help.

Portugal’s Fight Against Drugs

About 500 patients from Porto’s Cedofeita rehab center take methodone daily.

In 2008, the last year for which figures are available, more than 40,000 people used the rehab centers and other treatment programs, according to the Institute for Drugs and Drug Addiction, a branch of Portugal’s Ministry of Health. The ministry says it spends about €50 million ($64.5 million) a year on the treatment programs, with €20 million more provided through a charity funded by Portugal’s national lotteries.

Before decriminalization, Portugal was home to an estimated 100,000 problem heroin users, or 1% of the country’s population, says João Goulão, director of the Institute for Drugs and Drug Addiction. By 2008, chronic users for all substances had dropped to about 55,000, he says. The rate of HIV and hepatitis infection among drug users—common health issues associated with needle-sharing—has also fallen since the law’s 2001 rollout.

Portuguese and European Union officials are loath to give publicly funded treatment centers sole credit. They say the drop in problematic drug users could also be attributed to heroin’s declining popularity in Portugal and the rising popularity of cocaine and synthetic drugs among young people.

At the same time, Portugal’s drug-mortality rate, among Europe’s lowest, has risen. Mr. Goulão says this is due in part to improved methods of collecting statistics, but the number of drug-related fatalities can also be traced to mortality among those who became addicted to heroin during the country’s 1980s and 1990s epidemic.

Violent crime, too, has risen since the law’s passage. According to a 2009 report by the U.N. Office on Drugs and Crime, Portugal’s drug-use and murder rates rose in the years after decriminalization. The general rise in drug use was in keeping with European trends, but the U.N. noted with some alarm that cocaine use doubled and cocaine seizures jumped sevenfold from 2001 to 2006.

Murders rose 40% in the period. The report tentatively links that with drug trafficking, but points out overall murder rates in Portugal remain low.

Pedro do Carmo, deputy national director of Portugal’s judiciary police, says he doesn’t see link the rise in violent crime with decriminalization. Instead, he praises the program for reducing the fear and stigma attached with drug use. „Now, when we pick up an addict, we’re not picking up a criminal,“ he says. „They are more like victims.“

The Portuguese began considering drug decriminalization following a leap in heroin addiction decades ago in the country, a major entry point for drug trafficking from Latin America and North Africa.

The then-ruling Socialist Party government of Prime Minister António Guterres launched a political debate to discuss how to resolve the problem. Members of the right-wing People’s Party decried any tolerance for drug use, saying it would invite drug tourism.

Mr. Guterres’s government pushed through a full decriminalization law. A subsequent center-right coalition led by José Manuel Barroso, now president of the European Commission, didn’t repeal it.

The legislation was the first in a series of liberal policy shifts in this predominantly Roman Catholic country. In May, President Aníbal Cavaco Silva ratified a law allowing same-sex marriage, making it the sixth European country to do so. In 2007, Portugal went from having among the toughest restrictions on abortion to among the most liberal.

Portugal’s focus on close-knit community and protecting the family may be at the heart of many of these reforms, say some observers. In a 1999 report that paved the way for new drug legislation, current Portuguese Prime Minister José Sócrates implored that „drugs are not a problem for other people, for other families, for other people’s children.“

Portugal’s rehab clinics, called Centros de Atendimento de Toxicodependentes, are central to the strategy. In the lively northern port city of Porto, dozens of patients pop in daily to the Cedofeita rehab center to pick up free doses of methadone. Others have scheduled therapy or family counseling sessions, also free.

„The more they can be integrated in their families and their jobs, the better their chances of success,“ says José González, a psychiatrist at Cedofeita. Mr. González says that about half of his 1,500 patients are in substitution treatment, 500 of which take methadone daily. He says there is no defined model or timeline for treatment.

The European Monitoring Centre for Drugs and Drug Addiction, a Lisbon-based European Union agency, says methadone or other substance-substitution programs are generally viewed as successful but has observed that some Portuguese are beginning to question long-term methadone therapy.

„Now that the epidemic is under control for the most part, people start asking questions,“ says Dagmar Hedrich, a senior scientific analyst with the EMCDDA. „The question now is what is going to happen next? There is a part of the population who do not have the possibility of leaving the treatment.“

Very few studies have considered heroin users’ views on substitute prescribing, in
particular with regards to subutex. The aim of this study was to conduct detailed
qualitative analysis, using the Grounded theory approach, on heroin users’ views on
substitute prescribing, paying specific attention to methadone and subutex. Semistructured
interviews were conducted with nine subjects recruited from an
abstinence-based, structured day care treatment program. All of the subjects were
either currently on a subutex prescribing program, or had remained abstinent from
illicit substances following the completion of a subutex treatment program. Five major
themes emerged from the analysis. These were reasons for obtaining a methadone
prescription, experiences with methadone programs, views on methadone, views on
subutex and views on an ideal opioid treatment program. Most of the findings were
supported by previous qualitative studies such as that of Neale (1999a) and Fischer
and colleagues (2002). However, there does appear to be some discrepancies
between qualitative and quantitative research with regards to consumer satisfaction
of methadone, in comparison to subutex, as a substitute drug. This study clearly
highlights the need for further research into users’ views on substitute prescribing,
with emphasis being placed on qualitative research considering users’ experiences
with subutex.

Read the full File: methadoneversussubutex kopie

Methadone maintenance is somewhat of a mystery to clinicians not involved in addiction medicine, and opioid addicts don’t fare well in the emergency medical system. Many nurses and physicians have trouble dealing with them objectively and don’t want to be involved. Well-managed methadone maintenance is, however, a different story. Few EPs dole out methadone, but maintenance patients show up in the ED with legitimate complaints. Patients on high-dose methadone can experience painful conditions or injuries requiring additional analgesia. It’s not easy, but if one can put aside preconceived notions about addiction, methadone maintenance presents a fascinating challenge to the EP.

Figure. Clients line…

Most  have treated methadone maintenance therapy (MMT) clients in the ED, and have dealt with withdrawal, missed appointments, and overdose. I have visited a few methadone clinics, and the whole concept is fascinating, giving great insight into a government-sponsored medical entity.

Treatment Improvement Protocol Series 43: Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Program

This massive document summarizes the consensus of the U.S. Health and Human Services on MMT, which is administered through the Substance Abuse and Mental Health Services Administration and the Center for Substance Abuse Treatment, branches of HHS. This 14-chapter document has everything you want to know about MMT.

Edit by Exilope: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hssamhsatip&part=A82676

Initial Screening: Anyone can walk into an MMT clinic and request treatment. Initial screening exams and interviews determine the applicant’s eligibility and the process includes an assessment of their readiness to accept treatment. Ongoing, if not daily interventions, are required to keep the patient in the system and off the opioid. The addiction severity index collects basic information, and it can be used to track progress. Much of the information is supplied by the addict, and truthfulness on their part is paramount for success.

Comment: I suspect most people don’t walk in off the street thinking about MMT for the first time. All potential clients likely consider it many times or talk about it with fellow addicts. They are often prompted to try MMT by those who have been through the process, some more than one time. One would assume that an opioid addict who shows up at the clinic has hit rock bottom or finally has accepted they have an addiction they cannot control. Many are in overt withdrawal. They are ready to sign up.

First impressions are lasting ones. The HHS recommends a plethora of warm and fuzzy approaches to help the addict adjust and feel supported. A nonconfrontational and nonaccusatory attitude is stressed. Unlike the ED, MMT clinics want to be in the business of dispensing methadone. Clinics are usually prepared to provide immediate information, if not methadone treatment, on the first day.

A variety of preprinted documents are handed out that describe the services, rules, and expectations of the program. Policies are in place to deal with disruptive and violent clients and pregnant women. Clinics also try to identify treatment barriers and offer financial assistance and psychiatric crisis intervention. Many patients also have underlying psychiatric disorders, legal difficulties, child care issues, and transportation and family concerns. Cultural, ethical, and spiritual factors also complicate MMT. Those patients who seem in crisis can be referred for inpatient medical facility or psychiatric care. The correlation between opioid addiction and the risk of suicide is well known, and initial screening and periodic assessment helps determine that ongoing risk.

Admission Issues: A significant delay between the first contact, initial screening, and methadone treatment, especially failure to quickly address withdrawal, adversely affects the number of applicants who enter the program. It’s difficult to deal with an opioid addict in withdrawal; his patience wears thin, and he wants treatment now. Recognizing the realities of crowding and limited resources, MMT clinics can provide an interim maintenance program without formal screening or actual admission to the site. By federal regulation, medication can be administered for up to 120 days with only minimal screening procedures.

Violent or threatening patients can be turned down, but I have been amazed at how understanding and supportive some of the staff are; it’s similar to the mentality emergency physicians use to treat those who are not the nicest people. MMT, like emergency medicine, is a service industry, and the customers often possess the mentality of the McDonald’s client. They want it now, they want it their way, and they don’t want to pay much for it. Frustrated clients who elope are, however, a loss for everyone. Programs are not free, and cash and insurance are accepted, but often the down-and-out addict qualifies for local aid.

Information, Collection, and Dissemination: During the first few visits, a substance abuse history is obtained, and treatment options are discussed. Consent to treat is elicited, and addicts must sign a bevy of documents that provide further information on the multifaceted MMT process. Patients must be 18 or have parental approval. Otherwise, the services are confidential even to family members. Confidential information is not given to any inquiry except the court. The specifics of the individual’s opioid addiction, including recent pattern changes and binges, are gathered. Other drugs such as benzodiazepines and alcohol are often confounding issues, and the patient’s daily pattern of opioid abuse is determined, essentially by his own admission.

The opioid withdrawal history and the energy required to maintain the addiction is sought. Many patients are in withdrawal when they come to the clinic, making historical information open to exaggeration, but many downplay their use (like the alcohol history obtained in the ED). Some withhold a history of other addictions, perhaps thinking they might supplement the methadone if needed. Blood tests for specific drugs are not required nor usually performed to quantify use. A serum drug level is of no value in this scenario. Questioning the history can intimidate the prospective client and set up an adversarial relationship at the beginning. Again, unlike the ED, MMT clinics put a lot of trust in the truthfulness of the addict.

Medical Assessment: The aim of medical assessment is to determine the safety of methadone use. The drug is often dispensed on the first visit because of withdrawal. It is generally required that someone be addicted for one year before admission. There appears to be some flexibility in this criterium, especially for prisoners, pregnant women, or those previously treated. There may be uncertainty about past narcotic use, but generally a broad definition is accepted for opioid addiction, and one need not administer Narcan to test for withdrawal.

Generally, the staff obtains a medical history that documents drug-related diseases such as hepatitis, AIDS, tuberculosis, or STDs. Within 14 days of admission, a basic physical examination is performed, including blood tests for HIV, syphilis, and hepatitis. Federal regulations do not require a full panel of laboratory tests; that appears to be a state issue. Patients usually are tested randomly by a urine screen immunoassay test for additional drug abuse at least eight times each year per SAMHSA. Because methadone does not yield a positive opioid result unless specifically tested, a positive opioid screen usually means exogenous drugs.

Multiple Substance Abuse: It is common knowledge that opioid addicts often abuse other substances, especially alcohol, amphetamines, benzodiazepines, prescription opioids, cocaine, sedatives, and marijuana. CNS depressants are particularly dangerous when combined with opioids. Patients generally are asked to report other substances they used in the past. The accuracy of this form depends, of course, on patient honesty. Alcohol is a favorite of most, and heroin addicts particularly like to add cocaine for additional euphoria. Benzodiazepines are commonly used to boost methadone and enhance the high. Patients also self-medicate because of withdrawal symptoms or because they are anxious, depressed, or lonely.

MMT clients all know using an exogenous substance can kill them and defeat the purpose of MMT. Using exogenous drugs negatively affects attendance rates and cooperation with other programs. Interestingly, patients are not frequently discharged from MMT because they abuse other substances. The main goal is to retain the patient in MMT, allowing for human frailty, lack of self-control, and poor judgment. MMT clients are given multiple chances despite violating explicit rules and regulations.

Drug Testing: Clients are randomly tested for other drugs, usually with an immunoassay urine screen. This is not a perfect system because it only identifies those using other substances frequently and only detects drugs that show up on a urine screen. Of course, it has to be your urine, and there is always someone around who wants to give a clean sample for the right price.

Periodic drug testing provides objective evidence of treatment success and monitors patient progress. Typical urine testing evaluates for commonly abused substances with a qualitative immunoassay technique that has cutoff concentrations. Testing drug levels in the blood is not helpful because tolerance, time of use, and the need to send the test to a reference lab does not allow for meaningful interpretation of data. Most drugs remain in the system and are excreted in the urine for two to four days following use. Measuring methadone serum levels during treatment has minimal value and is not done routinely, but this may be used to identify a rapid or slow metabolizer. Obviously, urine tests are not quantitative; they merely give positive or negative results.

Urine collection may be monitored to avoid contamination or substitution. There are no firm and fast rules for the method of testing, and direct observation is not mandatory. The most common test is an enzyme-multiplied immunoassay technique (EMIT), which uses antibodies to specific drugs or metabolites. Oxycodone is often not identified with this test; nor are clonazepam, Seroquel, hallucinogens, fentanyl, Demerol, dextromethorphan, propoxyphene, and a variety of street drugs. On-site dipstick urine testing is common, but some clinics will confirm the initial clinic screen via a reference laboratory. Many clinics test patients at intake to prove they used opioids recently. The continued use of heroin or other opioids may prompt an increase in the methadone dose because it’s common to supplement during withdrawal.

Retaining Patients in MMT: The longer the patient stays in MMT, the less likely he will revert to using opioids. Staying in MMT for more than a year is associated with constructive lifestyles changes, decreased criminal behavior, and less transmission of infectious diseases. Older patients and those not in the criminal justice system tend to stay in the program longer. Those who have tried it before and failed are better candidates for retention the next time around.

But the key to MMT success, as this HHS publication notes, is: Adequate individualized medication dosages are probably the most important factor in patient retention because they contribute to patient comfort and satisfaction by reducing withdrawal symptoms and craving. The serum half-life of methadone is stated to be 24 to 36 hours, but in reality there is an extremely wide range (13-58 hours). Excessive methadone use occurs when daily visits and individual dose adjustment are not made.

Take-Home Medication: Methadone is usually dispensed daily in a liquid form, and ingestion is witnessed. This keeps patients from diverting tablets. Methadone diversion is a huge problem in this country, but that methadone is usually not obtained from clinics. A single take-home dose is common on Sundays and holidays. After six months to a year, compliant and reliable patients can take home one to four weeks of methadone, but initially, doses are only dispensed daily at the clinic. The requirement to show up every day can be problematic.

Figure. Christine Ad…

Dosing Schedule: A dose of 30 mg to 40 mg of methadone is the upper limit for the initial dose, per regulation. Initial dosing should be followed by increases over subsequent days until withdrawal symptoms are suppressed. A steady state of a dose is not reached for three to five, sometime seven days after a dosage change. The goal is to reach 80 mg to 120 mg methadone per day, a level that has been proven to improve compliance to the program. Using smaller doses or failing to increase the dose when withdrawal is still present is ineffectual and counterproductive. Withdrawal often prompts exogenous drug use or elopement.

The actual schedule is not set in stone, but daily dose increases of 5 mg to 10 mg a day for the first five to seven days to reach 60 mg a day are common. The 60 mg per day dose is maintained under daily observation to reach a steady state. The first week or two of MMT are the most dangerous for the patient and the time during which most fatalities occur. With daily observation and individual dose adjustments, induction is safe and effective as long as the patient is truthful and abstains from other drugs.

The quoted serum half-life of methadone can be misleading, and provides only a rough estimate to forecast dosing requirements and effectiveness. Methadone is eliminated more quickly from the blood and the effects wear off sooner until sufficient levels are obtained to saturate tissues, especially the liver. Smokers have increased clearance, and significant liver damage slows clearance. The optimal dose can only be determined by observing the individual daily, debriefing him on how he feels, and altering dosages in a safe, effective manner.

There is no uniformly suitable dose range or limit for all patients. Some require 400 mg to 700 mg a day while others do well on 80 mg to 120 mg a day. During induction, clinical observation and patient symptoms are the best indicators of whether a dose is too small or large. When this protocol is followed, methadone induction is safe and effective.

Comment: There are eight MMT clinics in Philadelphia, usually for heroin addiction, but more frequently for prescription opioid addiction. Most opioid addicts know the concepts of MMT well, and visit various clinics off and on throughout their addiction. The rules of MMT are straightforward, and each state is allowed some latitude on various issues. Some addicts have learned to work or abuse the system, but MMT is a godsend, if not a true lifeline, for many opioid addicts.

Addiction to hydrocodone, hydromorphone, and oxycodone is likely more widespread than street heroin. There is little difference between the prescription pill addict and the hardcore street heroin user on everyday issues or potential benefit from MMT. The well-to-do business man, the bored housewife, the professional athlete, or the Hollywood celebrity seem to prefer pills over the needle. Some physicians readily prescribe a slew of addicting medications, prescriptions are stolen or altered, and anyone can buy a few Percocet at the local high school. The Internet provides drugs as well as directions on use and how to beat drug tests and avoid overdose. Of course, heroin can be smoked and snorted as well, but there is less of a stigma involved with popping a pill than buying a bag of heroin on a lonely street corner.

I am quite impressed with the understanding approach to MMT and the dedication of the clinic personnel. Methadone manufacturers stress that their product should be used only under strict HHS guidelines, and they actually reference the Federal Register code in the package insert. The dangers of inappropriate methadone use are well-reported in the literature, but it’s likely an underused drug for chronic pain control.

Society has written off many opioid addicts or would drop them in a heartbeat at any sign of deceit or additional drug use. Not so for MMT clinics; they bend over backwards to give everyone yet another chance. Using additional substances during MMT is very common. Klonopin, Xanax, Soma, and Seroquel are popular in my area to boost methadone’s high, and none show on a urine screen. It’s easy to buy any of these on the street, usually right outside the door of the clinic. It’s best to never underestimate the ingenuity or resourcefulness of an opioid addict so MMT works best in an environment of mutual trust and truthfulness. Lying to the counselor about past or present drug use or beating the drug test is tempting, but in the end, it can be a fatal error.

people with addiction see a
primary care or urgent care
physician every 6 months, and many
others are regularly seen by other medical

These physicians are
therefore in a prime position to help patients
who may have drug abuse problems
by recognizing and diagnosing the
addiction, helping to direct patients to
a program that can meet their treatment
needs, and helping to monitor
progress after specialty treatment and
during recovery.3-6

Many physicians,
however, find the domain of drug abuse
particularly daunting and often avoid
the issue with their patients. This is understandable
given the relatively short
shrift drug abuse is given in formal
medical education. There is a widespread
misperception that drug abuse
treatment is not effective, which may
account for the reluctance of physicians
to even broach the subject of drug
abuse or treatment with their patients.
On the other hand, over the past 15
to 20 years, advances in science have
revolutionized our fundamental understanding
of the nature of drug abuse
and addiction and what to do about it.
In addition, there are now extensive
data showing that addiction is eminently
treatable if the treatment is welldelivered
and tailored to the needs of
the particular patient.

There is an array
of both behavioral and pharmacological
treatments that can effectively
reduce drug use, help manage drug
cravings and prevent relapses, and restore
people to productive functioning
in society.7-9
Of course, not all drug abuse treatments
are equally effective, and there
is no single treatment appropriate for
all patients. Fortunately, recent scientific
advances have provided insights
both into the nature of drug abuse and
addiction and into the principles that
characterize the most effective treatment
approaches and programs.10 These
treatment principles should make the
primary care or nonaddiction specialty
care physician’s tasks of screening
and referral much easier.

Read more: 20.03.10

Background: The objective of this research was to evaluate data from a randomized clinical trial that tested injectable
diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with
a Bayesian approach.
Methods: Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized
to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period
was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index
accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with
Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On
adding the data from the present study to update the a priori information, the distribution of the difference in response rates
were obtained and used to build credibility intervals and relevant probability computations.

Read more: heroin_vs_methadone_2_2009

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.

Read more: http://informahealthcare.com/doi/abs/10.1517/14740338.6.6.641

INTRODUCTION: Subjects using opioids on a chronic basis have been reported to have a high prevalence of abnormal sleep architecture and central sleep apnea (CSA). The severity of CSA is, in part, related to blood opioid concentration. The aim of this study was to investigate subjective daytime sleepiness and daytime function in patients who are on stable methadone maintenance treatment (MMT) and to assess the possible mechanisms involving abnormal sleep architecture, CSA severity, and blood methadone concentration. METHODS: Fifty patients on MMT and 20 normal control subjects matched for age and body mass index were tested using polysomnography, blood toxicology, Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire (FOSQ), and Beck Depression Inventory (BDI). RESULTS: The patients receiving MMT had significantly worse daytime function, were depressed, and had increased daytime sleepiness when compared with the control subjects (FOSQ 15.47 +/- 3.19 vs 19.4 +/- 0.47, BDI 14.64 +/- 10.58 vs 2.05 +/- 2.46, ESS 7.1 +/- 5 vs 2.05 +/- 1.76; all p values < 0.001). Nevertheless, daytime sleepiness in the patients receiving MMT was, on average, within the normal range (ESS < or = 10). Multiple regression analysis demonstrated that the severity of CSA, blood methadone concentration, and abnormalities in sleep architecture were not significant in predicting the variance of ESS or FOSQ (all p values > 0.05) in these patients receiving MMT. The BDI was the best predictive variable for FOSQ, explaining 16% of the variance (p = 0.004). CONCLUSIONS: Patients on stable MMT have, in general, normal subjective daytime sleepiness but impaired daytime function that partially relates to depression. The changes in sleep architecture, presence of CSA, and blood methadone concentrations do not significantly affect subjective daytime sleepiness and daytime function in these patients.

Study objectives: Methadone, a long-acting μ-opioid agonist, is an effective treatment for heroin addiction. Our previous data show that 6 of 10 methadone maintenance treatment (MMT) patients had central sleep apnea (CSA). This study aims to confirm these results and to investigate the pathogenesis of the CSA.

Methods: Twenty-five male and 25 female MMT patients and 20 age-, sex-, and body mass index (BMI)-matched normal subjects were tested with polysomnography, blood toxicology, and ventilatory responses to hypoxia and hypercapnia. Resting cardiorespiratory tests were performed in the MMT group

Results: MMT patients and normal subjects were 35 ± 9 years old (mean ± SD), and BMI values were 27 ± 6 kg/m2 and 27 ± 5 kg/m2, respectively. Thirty percent of MMT patients had a central apnea index (CAI) > 5, and 20% had a CAI > 10. All normal subjects had a CAI < 1, and no difference was found in obstructive apnea-hypopnea index between the two groups. Methadone blood concentration was the only significant variable (t = 2.33, p = 0.025) associated with CAI and explains 12% of the variance. Awake Paco2, antidepressant use, reduced ventilatory response to hypercapnia, and widened awake alveolar-arterial oxygen pressure gradient together explain a further 17% of the CAI variance.

Conclusions: Thirty percent of stable MMT patients have CSA, a minority of which can be explained by blood methadone concentration. Other physiologic variables may also play a role in the pathogenesis of CSA in MMT patients, and further research is indicated in this area.

The present review aims to clear up the issue of the neurological processes underlying the personality changes induced by chronic opioid use. The effects of methadone treatment on brain functions have been analyzed, too. Brain disintegration becomes evident very soon after an onset of chronic heroin abuse and continues throughout the period of drug consumption. A considerable proportion of opioid addicts are characterized by conspicuous neuropsychological deficits, which preclude the maintenance of complete opioid abstinence in this patient subgroup. At present, there are no data to testify that the effects of methadone maintenance on brain functions exceed the adverse neurological effects of chronic heroin use.

Polunina_9(2)2007 02.10.

MethadoneUsersandRiskydecisions 12

Reinforcing properties of psychoactive substances are considered to be critically involved in the development and maintenance of
substance dependence. While accumulating evidence suggests that the sensitivity to reinforcement values may generally be altered in
chronic substance users, relatively little is known about the influence reinforcing feedback exerts on ongoing decision-making in these
individuals. Decision-making was investigated using the Cambridge Risk Task, in which there is a conflict between an unlikely large reward
option and a likely small reward option. Responses on a given trial were analyzed with respect to the outcome on the previous trial,
providing a measure of the impact of prior feedback in modulating behavior. Five different groups were compared: (i) chronic
amphetamine users, (ii) chronic opiate users in methadone maintenance treatment (MMT), (iii) chronic users of illicit heroin, (iv) ex-drug
users who had been long-term amphetamine/opiate users but were abstinent from all drugs of abuse for at least 1 year and (v) matched
controls without a history of illicit substance use. Contrary to our predictions, choice preference was modified in response to feedback
only in opiate users enrolled in MMT. Following a loss, the MMT opiate group chose the likely small reward option significantly less
frequently than controls and heroin users. Our results suggest that different opiates are associated with distinctive behavioral responses
to feedback. These findings are discussed with respect to the different mechanisms of action of heroin and methadone.


An estimated 25 000 heroin addicts live in the Netherlands
(population 16 000 000 inhabitants).1 Most users
(75-90%) inhale heroin (“chasing the dragon”).2 About
three quarters of these addicts are served by a comprehensive
treatment system, including various kinds of
abstinence oriented treatment facilities and a wide
range of facilities focusing on stabilisation or
minimisation of harm.1 However, 5000-8000 people
on methadone maintenance treatment regularly use
illegal heroin, have serious physical and mental health
problems, and live in socially marginalised conditions,
characterised by illegal activities and a lack of social
contacts outside the drug scene.3–5
A large cohort study in Switzerland ascertained the
feasibility, safety, and efficacy ofmedical prescription of
injectable heroin to 1969 addicts. There were considerable
improvements in physical and mental health, various
aspects of social integration, and illegal drug use in
237 patients who completed 18 months of heroin
treatment.6 Although this study indicated that heroin
assisted substitution treatment is feasible, the effectiveness
of treatment was difficult to judge because no
(random) controls were available, before and after
comparisons were restricted to those who completed
treatment, and participants were obliged to take part in
mandatory psychosocial counselling and care.7–9 In a
small randomised controlled trial (n = 51) in which
intravenous heroin was compared with some standard
treatment, functioning of the participants in the heroin
group was significantly better after six months.10 However,
these positive effects could have been the result of
the additional, and mandatory, psychosocial interventions
in the group allocated to heroin.
We examined the effectiveness of medically coprescribed
heroine in two open label randomised controlled
trials among heroin addicts who had responded
insufficiently to methadone maintenance treatment.