Wednesday, September 29, 2010

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Today we have the cooperation of the member of ICAPSI, Dr. D. Francisco Javier Trujillo Carrillo, Psychiatrist he earned with his work "MAINTENANCE PROGRAM VS. METHADONE DETOXIFICATION IN PREGNANT junkie "Award City Council of Santa Cruz de Tenerife of the Royal Academy of Medicine for the best prevention and management of drug dependence.
The presented here is a summary of the author for the blog.
On behalf of the Institute, very cordial greeting.

Miguel Pérez-Camacho Duque
ICAPSI Director of


HISTORICAL may already since the time of the ancient Sumerians knew about the psychological effects of opium on the first clear references the effects of this substance we can find in the writings of Theophrastus in the S. III BC are the Arabs who are responsible for introducing into East medical use of the substance mainly for control of dysentery. Paracelsus popular in Europe makes use of this substance as a drug late fifteenth century and first half of XVI.
The word "opium" comes from Greek opion, diminutive of opos (formerly Hoposa), which means a vegetable juice or sap, referring to the milky juice that flows from the cuts made to the green capsules of opium poppy (Papaver somniferum ), a plant which is extracted from the raw material for the production of this substance.
opium alkaloids has over 20 different Setürner in 1806 isolated a pure substance from opium, which he called morphine, in reference to Morpheus, the Greek god of dreams. After the discovery of morphine were isolating other opium alkaloids (codeine by Robiquet in 1832, papaverine by Merck in 1848. In the mid-nineteenth century spread throughout the medical world the use of pure alkaloids, rather than existing opium preparations.
Given the technical difficulty of synthesizing morphine in labs, even today this drug is still extracted from opium. The milky juice (latex), which emanates from the sections from the green capsules of Papaver somniferum opium dries and becomes opium powder, which contains several alkaloids, only some of them have clinical utility, particularly morphine, which obtained the heroin, codeine and papaverine, these alkaloids can be classified into two major groups that are phenanthrenes and benzilisoquinolonas. Among the principal phenanthrenes have morphine, codeine and thebaine in the second group is papaverine, a smooth muscle relaxant, and noscapine.
Heroin, diacetylmorphine hydrochloride, was discovered by acetylation of morphine, and proved itself more effective than morphine or codeine. The pharmaceutical company Bayer started production in 1898 of heroin on a commercial scale. An employee of this company, H. Dresser, called the derivative of morphine "hero." There is no accurate documentation we discuss the origin of this name, it is thought that this name is due probably to the "heroic medicine" that is intended to provide the substance.
The first clinical results were very promising and proved more effective than codeine in respiratory diseases. However, repeated administration of heroin led to the development of tolerance in patients, and they soon became "addicted" to it, becoming more demanding of requirements and even coming to forging prescriptions to obtain the substance. At the beginning of last century, morphine addicts discovered the euphoric properties of heroin and this effect was reinforced by intravenous administration.
Heroin became a narcotic substance abuse and spread rapidly, so it took international treaties that regulate their production, use and distribution. In 1924, Congress of Import and Export of Narcotic Drugs banned the importation of opium for the manufacture of heroin. In 1925 the International Opium Convention imposed control mechanisms that began to limit the supply of heroin to Europe. Following these events, quickly began clandestine heroin produced in China. The supply of opium from the Far East became a real source of morphine (raw material for processing of heroin).
As a result of strict control after 1931 there was a significant decline in production and consumption, while beginning to look like business object by other social sectors began to investigate illegal production and trafficking. As an indicator of the global heroin market, the amount seized in the drug experienced dramatic growth in the decade of the 70. There are currently illegal distribution channels, including smugglers, dealers, vendors.
The medical use of heroin was not banned in America until July 1956, with the approval of Public Law 728, which seized all inventories for delivery to the Federal Government in November of that year. For the past 50 years, the list of countries supplying smuggled opium for heroin production has increased alarmingly. Opium used for heroin production into the United States currently comes from four main sources:
- The Golden Triangle, bordered by Burma, China and Laos.
- The Southwest Asia, recognized as providers in this country in the world: Turkey, Iraq, Iran, Afghanistan, Pakistan, India, Lebanon and the newly formed independent states of the former Soviet Union.
- America Central Mexico and Guatemala are the two main suppliers of heroin in Central America.
- South America: The production of heroin in this part of the world is relatively recent. There has been the cultivation of opium along the Andes, especially between Colombia in the areas of Cauca, Huila, Tolima and Santana.

producing areas have special geographical characteristics of temperature, rainfall and soil properties that make them ideal for the cultivation and opium production, however, there are qualitative differences in the crops of opium and morphine content of the various producing areas.
From a medical standpoint, this drug has generated Numerous studies and research, and today is one of the most important in day to day professionals engaged in substance abuse, both from a diagnostic point of view as a preventative and therapeutic.


As we mentioned in the previous section, the dependence on heroin in pregnancy is an aggravating element in the evolution and prognosis of the same. The prenatal effects of psychoactive substances on the fetus, especially its central nervous system, consisting of a biological vulnerability. Children born to mothers who abused substances during pregnancy have intrauterine growth retardation and neonatal neurobehavioral dysfunction (eg., irritability, difficulty in self care and alertness). The abuse of multiple substances, with poor nutrition, poor health and other intercurrent risk in this situation make it difficult to isolate the effects of a specific substance. Cocaine has been studied more selective and has been linked by vasoactive effects with abruptio placentae, premature labor, hemorrhage and cystic brain lesions, seizures, congenital abnormalities in the urogenital and gastrointestinal tracts and limb deformities. Opiate use during pregnancy directly affects the fetus and the newborn causing low birth weight and neonatal abstinence syndrome, which can stay with subacute up to 6 months, we must also take into account that a large proportion of pregnant women addicted to cocaine and heroin consumed in parallel with both drugs are excreted in small quantities in breast milk may cause or maintain the child dependency to these substances. Cannabis use during pregnancy has been associated with reduced fetal growth, reduced muscle mass development and lack of adipose tissue, following a pattern similar to that of infants of mothers consuming snuff. It has also shown a higher incidence of SIDS in the infant transitional anomalies and behavioral abnormalities. These children are at increased risk for various sexually transmitted diseases, including Acquired Immune Deficiency Syndrome (AIDS), hepatitis B or C if it is a consuming mother intravenously. It has also been shown to continue to have a very high risk of abuse and neglect after birth. When there are two situations: pregnancy and addiction to heroin, ideally, women abandon completely the use of any substance, legal or illegal, unfortunately the reality is different, programs outpatient drug-free patients often leave and resume the use of heroin, which the fetus is periodically subjected to situations of intoxication and withdrawal using the stress involved, and the risks of complications such as spontaneous abortion, stillbirth, prematurity and anomalies. Nor is it uncommon presentation of the patient at the time of delivery, without having previously received any medical or gynecological control and active consumption situation with a clear dependence on heroin. Children born in these conditions usually have a weight below 2.5 kg, which corresponds to a uterine growth retardation by direct action Heroin and other adverse circumstances such as the effects of having the drug adulterants, regular fetal hypoxia fetal suffering during times of abstinence from the mother, the lifestyle that often bring these patients, poor diet, infections, poor personal hygiene as well as little or no prenatal care. In these cases the newborn has a withdrawal syndrome, which in the case of women consuming heroin debut in the first 24 hours after birth. The main symptoms are vomiting, diarrhea, weight loss, irritability, hyperactivity sympathomimetic symptoms varying in intensity from mild to severe. Alternatives usual pharmacological treatment of heroin dependence, for example, the use of medication  2 adrenergic agonist or opioid antagonists have not been approved for use in pregnancy, the use of methadone for maintenance of the patient during pregnancy itself is approved, children are dependent on this substance at birth and require drug treatment if there has been adequate obstetric care during pregnancy, in principle there should be other problems. Should consider a methadone detoxification during pregnancy, it must be slow, we must bear in mind that if withdrawal occurs during the first quarter, is particularly troubling for fetal development, during the third quarter could precipitate premature labor. In case of withdrawal syndrome appear to methadone in the newborn, to have this substance have a longer half life than heroin, appears on the third or fourth day after birth, the symptoms are similar to those of withdrawal from heroin but less intense, but extend further in time.


The Methadone Maintenance Programs (MMP) developed by Dole and Nyswander since 1964, emerge as alternative treatments for opiate dependence. These authors maintained the existence of an endogenous dysregulation or molecular disorder at the Central Nervous System etiopathogenic basis of the dependency process of morphine or heroin addicts who had treatment-resistant with a tendency toward complete abstinence.
These conditions could only be balanced, according to these authors, by the continued administration of a legal opiate, methadone, with the main aim of getting the psychosocial rehabilitation of these patients, whereas abstinence, but should remain the ultimate goal was not always feasible in the short term.
The introduction of Methadone Maintenance Programs, marked a milestone in addressing opioid dependence, both for the innovativeness of the proposal, as to present a new conceptualization of the disorder itself, allowing a large number of addicts leave the heroin use, improve their health and quality of life and enabling family and social adaptation. Since then, the PMM has undergone many changes and is now viewed as essential therapeutic alternative in patients resistant management strategies and harm reduction.
In the last decade, the phenomenon of drug addiction has undergone major changes relacionados, fundamentalmente, con las nuevas problemáticas sanitarias y sociales asociadas al consumo de drogas por vía parenteral.
Cuando se iniciaron los PMM, la población dependiente de opiáceos se caracterizaba por consumir mayoritariamente heroína como droga primaria y presentar como principal motivo de preocupación sanitaria la hepatitis. Actualmente estos pacientes presentan, cada vez más, múltiples adicciones, principalmente alcohol, cocaína y ansiolíticos, a la vez que una morbilidad y marginalidad crecientes. Estas diferencias, fundamentalmente el aumento de la morbilidad ligada al SIDA han tenido un gran impacto en la totalidad de los programas de intervención en drogodependencias, y de una manera particularly on the Methadone Maintenance Program.
These programs have gained in recent years a progressive political commitment to reducing harm associated with addiction.


In recent decades, methadone maintenance treatment has proved to be most effective in the treatment of opioid dependence. Four randomized controlled studies have shown that methadone maintenance decreases illicit opioid use, criminal activity and adult mortality rates in heroin addicts. Although pregnant women were excluded from these randomized studies, from the 70 it is accepted that methadone maintenance is a therapeutic strategy for treatment of opioid dependence during pregnancy and has recently been recommended as the standard in the care of pregnant women dependent on opioids a Consensus Panel of the National Institute of Health American. The beneficial effects of methadone substitution therapy in adequate doses in pregnant women include, among others, protection of the fetus against the deleterious effects of sudden changes in blood concentration of opioids, improved medical monitoring of pregnancy, and prevention of prematurity and Newborn underweight.
The daily dose of methadone maintenance during pregnancy remains controversial and often based on an attempt to reduce or prevent the incidence of neonatal abstinence, rather than get an effective therapeutic dose. Recently, a study has analyzed the use of higher doses of methadone during pregnancy and its effect on women and the fetus, leading to the conclusion that it was associated with an increased risk in terms of symptoms of withdrawal in the neonate and yes, however, had a positive effect on maternal addiction. That is why, to limit arbitrarily the methadone dose, in an attempt to minimize the risk of occurrence withdrawal symptoms in the newborn, is not sufficiently supported in the literature. At the other extreme, it has been reported isolated cases of acute poisoning by uncontrolled and unusually high intake of methadone, resulting in death.
Several studies have shown that the metabolism of methadone in pregnant women is different from those not pregnant. During pregnancy, the placenta functions as an extrahepatic organ for biotransformation of drugs, although the amount and activity of enzymes in this case are lower than in the liver. The dose of methadone in the mother does not correlate with neonatal withdrawal and therefore the therapeutic benefits of a dose appropriate for the mother are not limited by the probable effect on the newborn.
There is controversy about whether methadone detoxification treatment in pregnant patients is safe or not. Despite the general tendency not to make the pregnant opioid detoxification in the second or third trimester of pregnancy, there is no clear evidence to support the concept that the removal of methadone is detrimental in opioid-dependent pregnant women. In a large series of 101 women addicted to opioids, methadone detoxification treatment was not associated with an increase in abortions in the second quarter and an increase of premature births in the third.
The effects on neonatal drug abuse by the mother include: weights, lengths and lower head circumference, increasing signs of CNS and autonomic nervous system, and an increase in the percentage of children referred to centers of child protection . In particular, opioid dependence has been associated at the time of birth with fetal death, low birth weight, prematurity, meconium aspiration and neonatal abstinence syndrome. Similar problems have been reported in methadone-dependent women during childbirth, although the occurrence of neonatal abstinence syndrome may be delayed for several weeks in this case. Some authors found that administration methadone to the mother has significant effects on fetal functions (heart rate, acceleration / deceleration periodic variability, motor activity, and link between fetal movements and heart rate) that are independent of the effects on the mother.
Most studies of pregnant heroin addicts in methadone treatment center on issues such as teratogenicity, prenatal and neonateles results, etc., It is interesting to see if the state of pregnancy may influence the development of heroin addicts in methadone treatment in this regard highlights a study conducted between 1999 and 2003 in a group of 102 patients in methadone treatment, 51 pregnant and 51 did not, we compared demographic characteristics, psychiatric comorbidity and retention rates and consumption within the program, while there were significant differences in demographic variables, retention and substance use, yes found a significant difference between psychiatric disorders, psychiatric comorbidity was observed more in the group of non embararazadas.
When comparing pregnant women who conceived and developed throughout the pregnancy under methadone treatment to those who began this treatment in the second or third trimester, relate better to the newly born in the first group of patients.
Finally, with regard to treatment withdrawal of the newborn, there is some heterogeneity in the therapeutic approach in the published literature. It seems clear that opioids are the preferred initial treatment, and in the last twenty years there are different jobs that support the use of morphine hydrochloride therapy recommended, over other drugs such as phenobarbital or diazepam.


As we discussed in previous sections, gestation in a patient becomes heroin addict, regardless of the problems directly related to the drug, such as low birth weight or the development of dependence in the fetus, in a high risk with an evolving and potentially adverse perinatal outcomes that will require some special care and follow all in relation to the style of life they lead these patients, the use of other substances, the risks of infections, poor health of the patient control, etc. The drug-free outpatient treatment, with non-opioid drugs are not indicated in these patients, thus making the methadone as one of the few valid therapeutic options with acceptable perinatal outcomes.
On the other hand, the fact administer treatment to ensure, practically from the beginning, the physical welfare of the patient, creates a greater recruitment of the same and less likely to abandon the program, which will encourage other interventions, not only in the health area, but also in psychological and social, are often severely affected, thereby providing comprehensive assistance to this complex problem.
There is no universal agreement on what treatment regimen to do, but we accept two major approaches: 1) Methadone maintenance and 2) methadone detoxification. In this paper we, prospectively, to study the results of one form or another treatment in a group of pregnant women heroin users.
There are few publications that analyze the perinatal results of these treatments. With this work we established the following objectives:
1) To verify the clinical efficacy and variability of these types of treatment in pregnant heroin users.
2) analyze the perinatal outcome in both treatments.
3) develop a protocol for comprehensive care for these patients.


PATIENTS Between January 2004 and October 2007 were prospectively recruited to carry out this work a total of 94 patients treated pregnant heroin users Methadone sent to Hospital Universitario de Canarias (HUC), according to protocol established between the referral assistance of gestation at high risk of addiction, HIV, Department of Obstetrics and HUC Care Centers Drug Addiction in Tenerife (CAD). From this initial group led to the birth care in the same hospital a total of 80 patients constituting the final study group. The remaining 14 patients were eliminated from the study because of spontaneous abortion (6 patients) or lack of follow-up protocol (8 patients). Once evaluated
toxic and clinical criteria were included in a first group (Group 1) to 30 pregnant women for program Methadone maintenance and a second group (Group 2) to 50 pregnant for methadone detoxification program.
The age of these patients are presented in Table I. Displaying patients of all ages and groups, no significant differences.
Regarding medical history found in the groups studied in Group 1 highlight an incidence of 26% positive for antibodies to hepatitis B and 25% against hepatitis C, found no antibodies for HIV. In one case of heart disease and the rest of the sample had no relevant medical history. In Group 2 showed an incidence of 23% of antibodies against hepatitis B and 19% against hepatitis C, there was a case of antibodies to HIV and one case of chronic obstructive pulmonary disease, the rest of the sample showed no relevant medical history.
As a gynecological history of patients referred, 88% of pregnant members of Group 1 had no history of interest in the same way that 89% in Group 2, no significant differences between the two samples this variable (p = 0.55), two pregnant women in the first group and one in the second, had a history of intrauterine fetal death.
The review of the obstetric history of patients shows no difference when analyzing the gesture (p = 0.66), parity (p = 0.63), number of previous abortions (p = 0.88) and the number of abortions (p = 0.33). Respect
drug profile of patients, 85% were consumers of snuff in Group 1 and 79.5% in Group 2. Heroin as the only drug of abuse was found in only 11% of pregnant women in the maintenance program and 7% of the group of detoxification. The majority of consumer profile in both groups was consistent with a pattern of polydrug use, collecting the background of the use of two or more substances in 89% of cases belonging to Group 1 and 93% for Group 2. The main drugs of abuse in Group 1, in addition to heroin and snuff, and in order of frequency were: cannabis (44%), cocaine (41%), alcohol and psychotropic drugs (18.5% both). As regards Group 2, the order of frequency is: cocaine (75%), cannabis (68%), alcohol (41%) and psychotropic drugs (36%). METHODS

The criteria for inclusion of pregnant women in the group of maintenance or detoxification group based in several respects. One of the most important is the assessment of the patient's social and family situation (whether or not of support at the time of starting treatment). Others are the presence of organic or psychiatric illnesses that contraindicate a detox, the age of consumption, the amount of heroin, gestational age at diagnosis of drug dependence (as it was not well known before pregnancy). The evaluation of patients prior to the award of a maintenance or detoxification is undertaken on a multidisciplinary, comprehensive analysis in a case.
regard to methadone maintenance program, as referred in the Introduction, there is currently no consensus on it regarding the optimal dose. In our study, so parallel to the most recent publications, the treatment was instituted with the minimum effective starting dose, meaning that minimum dose in which the patient feels no physical or psychological discomfort or craving. For its part, the detoxification program is designed individually, starting in each case a gradual decrease in dose, depending on the presenting symptoms during pregnancy. In patients with starting dose medium-low (≤ 30 mg / day) was started detoxification from week 32, those with higher initial doses, is beginning earlier. The decrease of the dose is provided weekly.
The approach drug involves a multidisciplinary intervention. Apart from a higher administrative expense and effort, a pregnancy of these characteristics requires a greater number of queries from therapists who follow the case (doctors, psychologists, nurses, etc.), On the other hand, it is a major expense in reagents Laboratory monitoring of urine more frequently and more broadly, since it must control the withdrawal of more substances are potentially harmful to fetal development (opiates, cocaine, benzodiazepines, amphetamines and derivatives, cannabis, etc.). There is also a greater analytical control of blood parameters (hemogram, comprehensive study of iron, serology for hepatitis, HIV, syphilis, etc., biochemical complete, especially lipid profiles and blood glucose).
not forget that the control and monitoring gynecological high-risk pregnancy, as is the question, requires a gynecological increase with respect to a normal pregnancy and a greater number of tests (ultrasound, records CTG, preterm birth screening, etc.).

DISCUSSION Factors affecting directly and indirectly the health of pregnant women and newborns are multiple, should be taken into account in the obstetric management. Drug use has been an increase in women of childbearing age and pregnant, and has significant medical and social consequences. Multidisciplinary teams are needed tolerant and free from prejudices about this social problem, which act not only during pregnancy and the neonatal period, but long term. The main drugs of abuse are illegal opiates (heroin, methadone), cannabis and cocaine. Far from the traditional consumption patterns, currently dominates the pattern of polydrug use, meaning that the simultaneous use of two or more substances. Opioid dependence during pregnancy represents a special problem for the health system are well known because of the serious consequences for the mother and fetus. In a recently published work which examined a large series of pregnant patients who used opioids, the prematurity rate was as high as 30% and neonatal deaths a figure of 18/1000 infants.
As mentioned in the last 30-40 years, methadone maintenance has proved to be the most effective treatment for opioid dependence. With the substitution therapy with methadone to pregnant women, in addition to protecting the fetus from the stress of constant changes in concentration of opiates, the adverse effects and suffering Fetal that this entails, we provide the patient a better medical management of pregnancy, both from the point of view of addiction as from the obstetrical point of view, so is best prevented prematurity, low birth weight and other intercurrent complications in pregnancy while involved in other areas so affected in these patients such as family and social and psychological.
also recently reported good results when replacement therapy is high dose buprenorphine instead of methadone, and even some work (though not randomized) gives more advantages to this drug.
still remains a matter of controversy appropriate maintenance doses in pregnant heroin users in many cases still prevailing approach to prevent withdrawal symptoms in the neonate on to achieve an effective dose to eliminate maternal distress. Recent studies of pregnant women with high doses of methadone have found no relationship between dose and severity in the effects of withdrawal in the newborn, as limiting the doses of methadone in pregnant women to avoid the appearance of withdrawal symptoms in the newborn, is not sufficiently supported in the literature. As noted in the results of our study, with a low incidence of neonatal abstinence syndrome, the appearance the same could not be correlated with methadone dose received by the mother during childbirth.
Other recent studies have come to lead on this occasion to find no positive association between methadone dose received by the mother and the severity of neonatal abstinence syndrome. It makes us think, also according to our study, the lack of justification for the commitment to detoxification with methadone in cases which were not recommended.
In another sense, the tendency not to detoxify pregnant patients in the second or third quarter, preventing the complications of maternal withdrawal, it is not clear. As discussed in the treatment section in a series of 101 pregnant women addicted to opiates receiving methadone detoxification treatment, there was no increase in abortions in the second quarter and increased rate of prematurity in the third quarter. In our study, treatment with methadone detoxification has not been at any time associated with an adverse outcome on fetal development with employees monitoring methods (ultrasound and cardiotocography registration), the behavior of the fetus during labor and perinatal outcome .
regard to the effects described that may lead to opioids in the newborn such as fetal death, weight loss at birth, prematurity, meconium aspiration and neonatal abstinence syndrome in the group of methadone patients in our study can not speak at all about the existence of this pathological association. Special mention must
only adverse perinatal outcome in our series that corresponded to a patient of 27 years, hepatitis B and C positive, in keeping with 15 mg of methadone, whose pregnancy was uneventful and entering labor, detected at that time the patient died of the fetus which weighed 3200 gr. This means that this is a case of intrauterine exitus of unknown cause, possibly related to a cable car accident the absence of further clinical evidence. In any case, not in this case signs that might suggest that this painful outcome may be related to use pathology at hand.
We found in both study groups the incidence of prematurity, a variable that has traditionally presented high values \u200b\u200bin pregnant heroin users, can be equated to that of the general population of our country. The same observation can do other variables also referred to as the greatest impact on this type of pregnant women, we now refer to the prevalence of diabetes during pregnancy (especially urinary tract infections, lower genital tract and anemia), greater incidence of disorders in fetal development (intrauterine growth retardation and / or decrease the amount of amniotic fluid and / or greater degree of placental aging) and, finally, low birth weight.
The most plausible reason we can claim to give an explanation for these results can be found in the "normalization" of these patients leads to real equality to the general population in obstetric and perinatal outcomes. Once again we must insist that this is a complex and multidisciplinary and that the term "normalization" we used refers not only to the medical aspects (Detection and treatment of disease, mineral supplementation, diet correction, etc..), But other areas of psychosocial nature will also make these patients eligible for follow-up plans of their pregnancy to correct social status variables and family which significantly hinder the successful development and outcome of pregnancy.
Finally, although the present study can be considered preliminary, requiring a larger sample, we can deduce from the results that there are important differences between a form or another for the treatment of heroin addiction in pregnant women. We should note that the indication treatment or the other should always be assessed individually based on a multidisciplinary analysis, and the loyalty of pregnant women to such treatment is a fundamental aspect that must prevail over fear to handle high doses of methadone. Neither our work nor in most of the literature, correlation was found between the dose of methadone and pathology during pregnancy, or between the dose at the end of pregnancy and poor perinatal outcomes, including abstinence syndrome neonate.


1. In the series of pregnant heroin users studied by us have found results in the development of pregnancy, during delivery and perinatal that no significant variation with respect to the general population of pregnant women in our midst.
2. The monitoring protocols high-risk pregnancy and delivery care in these patients followed, according to the comments on the finding number 1, have been shown clinically effective.
3. These favorable results were obtained with a peer group both in detoxification and methadone maintenance.
4. The methadone abstinence syndrome in the newborn, we have found in 12%, failed to correlate with the dose of methadone ingested by the mother during childbirth.
5. In the group of pregnant women treated with methadone detoxification program is able to reduce the dose of the same until total suspension in 25% of patients. However, the rest could be reduced considerably administered methadone (average 62% of the initial dose).
6. In the patient group targeted at methadone maintenance plan according to established criteria had to increase the initial dose in 59% of cases (with an average increase of 48% compared to the initial dose).
7. According to the above, we believe that in the clinical management of these patients should prevail getting a physical state with the required dose of methadone detoxification against thereof.
8. The cause of the good results we found that due to the multidisciplinary approach to these patients.


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