**1. Introduction**

The opiates, especially the heroin could be the main problem in the matter of drugs at world level, as statistics on the treatment request show. Heroin use dominates the demand for treatment in Europe (around 80% of new opioid-related treatment demands) [1]. However, the opiates consuming is relatively stable at the world level, with an estimated 33 million users of opiates and prescription opioids, according to the latest world report on drugs [2]. European

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

statistics show that heroin is the most commonly used illicit opioid in Europe, but synthetic opioids such as methadone, buprenorphine, and fentanyl are also misused. The average prevalence of high-risk opioid use among general EU population (15–64 years) is estimated at 0.4%, the equivalent of 1.3 million high-risk opioid users in Europe in 2015 [1].

The methadone maintenance therapy (MMT) is an intervention of harm reduction type, because the patient does not become abstinent (i.e., the patient does not cure, i.e., he/ she does not give up any substance consumption); instead, a series of positive changes such as managing opioid withdrawal, reducing craving, returning to a job, education, and a family happens [11]. The methadone is orally administrated and due to its halflife, between 24 and 36 hours, it may be administered once a day. Administered in doses of 80–120 mg/a day (adjustments are possible according to each patient), the methadone blocks the euphoric effects of the heroin, and moreover, eliminates the craving for heroin; they are some of the most important factors in case of relapses. Methadone maintenance programs decrease mortality by approximately 50% among persons with opioid-use disorders, decreased prevalence of significant infections such as HIV and hepatitis, decrease crime, reduces illicit opioid use, improve social functioning, and increase the rate of reten-

Methadone Treatment for Heroin Dependence http://dx.doi.org/10.5772/intechopen.78066 119

The use of the methadone in the substitution treatment of the patients addicted to opiates is well-documented and its efficacy is well established but responses vary. Despite successful outcomes, the MMT and the influence of methadone pharmacodynamics and pharmacokinetics on dose requirements continue to remain controversial [13]. A relationship between methadone dose and plasma methadone concentration in addicted patients during substitution therapy has been suggested, the plasma level depends on different factors [14, 15]. However, research conducted so far have demonstrated fully and unequivocally follows: patients receiving inadequate doses of methadone will continue to use heroin; these patients do not respond to behavioral therapies or they need maintenance treatment with methadone for long periods; when doses of methadone are tailored and individualized favorable trends are observed in these patients [16, 17, 18]. Optimal treatment can only be determined if one takes into account the factors that determine differences in drug response and only when the dosage is determined based on diagnosis, severity, and stage of the disease and on the presence of other diseases or concomitant therapy. This allows pre-evaluation of efficacy and acceptable toxicity limits. If these assessments are not done properly before treatment, if patients are not appropriately monitored during treatment,

In this context, we conducted a study, on a period of a year, on a group of patients with a diagnosis of heroin addiction, who have voluntarily submitted to an addiction treatment center in Bucharest, for inclusion in the program of methadone substitution treatment. The objective of the study was to define the profile of the patient entering the methadone substitution therapy

The group to be studied consisted of 82 drug addicts, consumers of heroin; these patients were examined from the psychological point of view at the Addiction Section, were hospitalized and monitored during the detoxification which was carried inpatient, under strict medical supervision, for a period of 10–14 days, then in the outpatient treatment (methadone

tion in rehabilitation programs [12].

there is a risk that the therapy to be ineffective.

and to evaluate the adherence to treatment.

**2. Study design**

In addition, opioids remain major drugs of potential harm and health consequences. There are several complications, which are derived from the illicit opioids consumption, among which there are overdoses, transmissible infections, the increase of criminality, reduction of workforce, and general life quality [3, 4].

The addiction to opioids, a complex disease, necessitates a long-term treatment, which mainly consists in the substitution therapy, also called, according to WHO, "agonist pharmacotherapy," "agonist replacement therapy" or "agonist-assisted therapy"; this is a key component of the treatment resources [5]. WHO defines it as the administration under medical supervision of prescription psychoactive substances, which are pharmacologically related to the one producing dependence, to people with addiction, for achieving defined treatment goals.

Several tries of substitution treatments of the opiates addiction took place at the beginning of the twentieth century and they used the morphine. The morphine did not prove to be a corresponding substance for substitution (tolerance used to rapidly install, the patient needed to have several injections per day). Since 1960s, starting with the discovery of the methadone, the substitution treatment began to be reevaluated.

In 2005, WHO added methadone and buprenorphine in the list of essential drugs for the treatment of opioid dependence [6]. This decision was based on numerous studies that have shown that using these two drugs in substitution therapy bring benefits for physical and mental health, improves quality of life, and reduces injection behaviors associated with high risks. Therefore, international guidelines recommend methadone and buprenorphine as first-line medication treatment for opioid dependence [7]. The studies were conducted in countries with different socio-economic conditions and different treatment systems for drug addiction. These studies have shown that therapy with methadone or buprenorphine is safe and effective [5]. The substitution therapy with methadone or buprenorphine gives addicted people the possibility to function normally within their families, jobs, and communities [8]. However, methadone was shown to have higher treatment retention rates than buprenorphine-naloxone, and it is preferred over buprenorphine-naloxone for patients at higher risk of treatment dropout [9].

A standard terminology for the treatment with methadone, classified into four categories, has been proposed:


Usually, the term "substitution therapy" is utilized as an equivalent to "substitution maintenance therapy" [10].

The methadone maintenance therapy (MMT) is an intervention of harm reduction type, because the patient does not become abstinent (i.e., the patient does not cure, i.e., he/ she does not give up any substance consumption); instead, a series of positive changes such as managing opioid withdrawal, reducing craving, returning to a job, education, and a family happens [11]. The methadone is orally administrated and due to its halflife, between 24 and 36 hours, it may be administered once a day. Administered in doses of 80–120 mg/a day (adjustments are possible according to each patient), the methadone blocks the euphoric effects of the heroin, and moreover, eliminates the craving for heroin; they are some of the most important factors in case of relapses. Methadone maintenance programs decrease mortality by approximately 50% among persons with opioid-use disorders, decreased prevalence of significant infections such as HIV and hepatitis, decrease crime, reduces illicit opioid use, improve social functioning, and increase the rate of retention in rehabilitation programs [12].

The use of the methadone in the substitution treatment of the patients addicted to opiates is well-documented and its efficacy is well established but responses vary. Despite successful outcomes, the MMT and the influence of methadone pharmacodynamics and pharmacokinetics on dose requirements continue to remain controversial [13]. A relationship between methadone dose and plasma methadone concentration in addicted patients during substitution therapy has been suggested, the plasma level depends on different factors [14, 15]. However, research conducted so far have demonstrated fully and unequivocally follows: patients receiving inadequate doses of methadone will continue to use heroin; these patients do not respond to behavioral therapies or they need maintenance treatment with methadone for long periods; when doses of methadone are tailored and individualized favorable trends are observed in these patients [16, 17, 18]. Optimal treatment can only be determined if one takes into account the factors that determine differences in drug response and only when the dosage is determined based on diagnosis, severity, and stage of the disease and on the presence of other diseases or concomitant therapy. This allows pre-evaluation of efficacy and acceptable toxicity limits. If these assessments are not done properly before treatment, if patients are not appropriately monitored during treatment, there is a risk that the therapy to be ineffective.

In this context, we conducted a study, on a period of a year, on a group of patients with a diagnosis of heroin addiction, who have voluntarily submitted to an addiction treatment center in Bucharest, for inclusion in the program of methadone substitution treatment. The objective of the study was to define the profile of the patient entering the methadone substitution therapy and to evaluate the adherence to treatment.
