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      Pharmacologic treatments for opioid dependence: detoxification and maintenance options Translated title: Tratamientos farmacológicos para la dependencia de opioides: opciones para la detoxificación y el mantenimiento Translated title: Traitements pharmacologiques de la dépendance aux opioïdes: détoxification et traitement d'entretien

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          Abstract

          While opioid dependence has more treatment agents available than other abused drugs, none are curative. They can, however, markedly diminish withdrawal symptoms and craving, and block opioid effects due to lapses.

          The most effective withdrawal method is substituting and tapering methadone or buprenorphine, α-2 Adrenergic agents can ameliorate untreated symptoms or substitute for agonists if not available. Shortening withdrawal by precipitating it with narcotic antagonists has been studied, but the methods are plagued by safety issues or persisting symptoms. Neither the withdrawal agents nor the methods are associated with better long-term outcome, which appears mostly related to post-detoxification treatment.

          Excluding those with short-term habits, the best outcome occurs with long-term maintenance on methadone or buprenorphine accompanied by appropriate psychosocial interventions. Those with strong external motivation may do well on the antagonist naltrexone. Currently, optimum duration of maintenance on either is unclear. Better agents are needed to impact the brain changes related to addiction.

          Translated abstract

          Aun cuando la dependencia de opioides tiene más agentes terapéuticos disponibles que otras drogas de abuso, ninguno de ellos resulta curativo. Sin embargo, estos agentes pueden disminuir marcadamente los síntomas de abstinencia y el craving, y bloquear los efectos de los opioides debidos a las recaídas. El metodo más efectivo para tratar la abstinencia es la sustitución y disminución progresiva con metadona o buprenorfina. Los agentes α-2 adrenérgicos pueden reducir los síntomas no tratados o reemplazar a los agonistas si no se dispone de ellos. Se ha estudiado la reducción del período de abstinencia utilizando antagonistas narcóticos, pero los temas de seguridad o de la persistencia de síntomas han dificultado su desarrollo. La mejor evolución a largo plazo no se relaciona ni con los metodos ni con los agentes usados para manejar la abstinencia, sino que se asocia con el tratamiento post-detoxificación. Excluyendo a aquellos pacientes que cambian de hábito en el corto plazo, la mejor evolución ocurre cuando se mantiene metadona o buprenorfina a largo plazo, junto con adecuadas intervenciones psicosociales. En aquellos pacientes con una fuerte motivación externa puede ser útil el uso del antagonista naltrexona. Actualmente no hay claridad respecto a la duración de los tratamientos de mantenimiento. Se require de mejores agentes para combatir los cambios cerebrales relacionados con la adicción.

          Translated abstract

          Les traitements de la dépendance aux opioides, bien que plus nombreux que ceux des autres substances addictogènes, ne sont pas curatifs. Ils peuvent néanmoins diminuer notablement les symptômes de sevrage et la compulsion de consommation et bloquer les effets opioides dus aux récidives.

          La méthode de sevrage la plus efficace est celle de la substitution et de la réduction progressive par la méthadone et la buprénorphine. Les agents α-2 adrénergiques peuvent améliorer les symptômes non traités ou remplacer les agonistes s'ils ne sont pas disponibles, On a cherché à raccourcir la période de sevrage en la déclenchant par des antagonistes narcotiques mais des problèmes de tolérance ou de persistance des symptômes en ont gêné le déroulement. L'amélioration à long terme n'est liée ni aux produits de sevrage ni aux méthodes mais plutôt au traitement qui suit la détoxification.

          En excluant les produits avec lesquels I'accoutumance survient à court terme, les meilleurs résultats sont obtenus avec le maintien au long cours de la méthadone ou de la buprénorphine accompagné d'interventions psychosociales adaptées. Les patients dont la motivation externe est forte pourront préférer l'antagoniste naltrexone. Actuellement, la durée optimale de maintien de l'un ou de l'autre n'est pas bien définie. De meilleurs produits sont attendus pour traiter les modifications cérébrales liées à la dépendance.

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          Most cited references174

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          Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial.

          Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited. To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients. A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection. An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention. The event rate of heavy drinking days in the intent-to-treat population. Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups. Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence.
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            An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research.

            To summarize the major findings of the five Cochrane reviews on substitution maintenance treatments for opioid dependence. We conducted a narrative and quantitative summary of systematic review findings. There were 52 studies included in the original reviews (12,075 participants, range 577-5894): methadone maintenance treatment (MMT) was compared with methadone detoxification treatment (MDT), no treatment, different dosages of MMT, buprenorphine maintenance treatment (BMT), heroin maintenance treatment (HMT), and l-alpha-acetylmethadol (LAAM) maintenance treatment (LMT). Outcomes considered were retention in treatment, use of heroin and other drugs during treatment, mortality, criminal activity, and quality of life. Retention in treatment: MMT is more effective than MDT, no treatment, BMT, LMT, and heroin plus methadone. MMT proved to be less effective than injected heroin alone. High doses of methadone are more effective than medium and low doses. Use of heroin: MMT is more effective than waiting list, less effective than LAAM, and not different from injected heroin. No significant results were available for mortality and criminal activity. These findings confirm that MMT at appropriate doses is the most effective in retaining patients in treatment and suppressing heroin use but show weak evidence of effectiveness toward other relevant outcomes. Future clinical trials should collect data on a broad range of health outcomes and recruit participants from heterogeneous practice settings and social contexts to increase generalizability of results.
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              Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.

              Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                Professor of Psychiatry, Columbia University College of Physicians & Surgeons, NY, USA; Director, Division on Substance Abuse, The New York State Psychiatric Institute, NY, USA
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                December 2007
                December 2007
                : 9
                : 4
                : 455-470
                Affiliations
                Professor of Psychiatry, Columbia University College of Physicians & Surgeons, NY, USA; Director, Division on Substance Abuse, The New York State Psychiatric Institute, NY, USA
                Author notes
                Article
                10.31887/DCNS.2007.9.2/hkleber
                3202507
                18286804
                3ba16866-87e5-44d7-826e-2f697fe96e0e
                Copyright: © 2007 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Pharmacological Aspects

                Neurosciences
                maintenance,methadone,clonidine,opioid dependence,pharmacologic treatment,detoxification,naltrexone,buprenorphine

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