Maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Clinical studies indicate that about a third of patients in opioid maintenance therapy show increased alcohol consumption and alcohol use disorders. Comorbid alcohol use disorders have been identified as a risk factor for clinical outcome and can cause poor physical and mental health, including liver disorders, noncompliance, social deterioration and increased mortality risk. The effects of opioid maintenance therapy on alcohol consumption are controversial and no clear pattern has emerged. Most studies have not found a change in alcohol use after initiation of maintenance therapy. Methadone and buprenorphine appear to carry little risk of liver toxicity, but further research on this topic is required. Recent data indicate that brief intervention strategies may help reduce alcohol intake, but the existing evidence is still limited. This review discusses further clinical implications of alcohol use disorders in opioid dependence.

Epidemiology of Alcohol Use Disorders in Opioid Dependence

Substance use disorders, including opioid dependence, are defined by a cluster of somatic, psychological and behavioral symptoms. The worldwide prevalence of opioid use disorders is 0.4%, and about 12 million people use heroin worldwide [1, 2, 3]. In Europe, about 1.35 million individuals are affected [1]. In the USA, the 12-month prevalence of drug abuse was recently estimated at 5.7% [4]. Approximately 3.7 million individuals have used heroin at least once in their lives and 750,000-1,000,000 individuals are currently heroin dependent [5].

Opioid dependence is frequently associated with polysubstance use and alcohol use disorders (AUD), and the latter cause multiple health and social problems [3, 6, 7, 8]. This paper presents a comprehensive review of the existing literature on the prevalence and treatment of AUD in opioid dependence.

Opioid and alcohol abuse and dependence show some close neurobiological interrelations. In brief, like other drugs of abuse both alcohol and opioids induce dopamine release in the ventral tegmental area and nucleus accumbens; the psychotropic effects of alcohol are in part mediated via the opioid-endorphin system [9, 10, 11]. Alcohol stimulates the release of beta-endorphin, enkephalins and dynorphin [12, 13, 14, 15, 16], and opioids stimulate alcohol intake via the paraventricular nucleus [17]. Opioid receptor blockade decreases alcohol intake [18, 19, 20, 21]. Studies have provided broad evidence for a significant role of the opioid system in mediating the reinforcing effects of alcohol and the associated dopamine release in the mesolimbic brain area [15, 19, 22, 23, 24, 25, 26].

Clinically, both alcohol and opioids are ‘downers', i.e. they have a strong sedative effect and cause respiratory depression. Many studies have addressed the possible role of mu-opioid receptor polymorphisms in mediating the genetic risk for alcohol or substance use in general. The OPRM1 variant was found in a recent meta-analysis to have a modest protective effect on the risk for substance use in comparison to the 1799971 (A118G ASN40/ASP40) G allele [27]. This gene variant may modulate treatment response to the opioid antagonist naltrexone, which is used for alcohol treatment [28]. ASP40-ASN40 heterozygotes may respond better than ASP40 homozygotes to naltrexone [29].

A systematic literature search was performed in the Medline and Pubmed databases to identify clinical and epidemiogical studies on a possible association between opioid dependence and AUD. The search was not limited to certain years or languages. The indexing terms were ‘methadone AND alcoholism' (402 citations) and ‘buprenorphine AND alcoholism' (48 citations). In addition, the terms ‘opioids and alcohol' were screened. Papers focusing on epidemiology, diagnosis, therapy or other clinical issues were considered to be of special relevance.

A patient may present with the typical clinical picture of being intoxicated or generally drinking too much, i.e. alcohol breath, increased body sway, red skin, CNS symptoms such as irritability, anxiety and restlessness, or, in more severe cases, withdrawal symptoms such as sweating, tremor, tachycardia or increased blood pressure (table 1). A breathalyzer may help to verify alcohol consumption. Increased liver enzymes can also help to identify patients, but they have low specificity because many patients have hepatitis or other liver disorders. Increased mean corpuscular volume (MCV) or carbohydrate-deficient transferrin values are other relevant biomarkers for alcoholism [30, 31, 32]. More recently, direct alcohol metabolites, especially ethyl glucuronide, was reported to be useful for measuring alcohol consumption in patients on opioid maintenance therapy [33, 34, 35]. Also, the 5HTOL/HIAA ratio in urine was used to detect alcoholism in methadone maintenance patients [36].

Table 1

Detection of alcoholism in opioid dependence

Detection of alcoholism in opioid dependence
Detection of alcoholism in opioid dependence

The standardized Addiction Severity Index (ASI) interview or its European variant, the EuropASI [37], can be used in clinical studies to identify alcohol problems. The Alcohol Use Disorder Identification Test (AUDIT, 10 items) [38, 39] is recommended by the WHO for clinical use and to screen patients, and is frequently used in clinical studies (see below).

Prevalence estimates for AUD in opioid dependence vary. Approximately one third of the patients in methadone treatment are assumed to have alcohol problems [40, 41, 42]. More recent data by and large confirm these findings. An Irish study estimated the prevalence of problem alcohol use among patients attending primary care for methadone treatment at 35% [43]. Data from the British National Treatment Outcome Research Study (NTORS) suggest that almost half of the patients in residential programs drink alcohol and just over a third of those in community programs drink above the recommended levels [6]. A Swiss 2-year longitudinal study found occasional alcohol abuse in 38-47% of methadone patients and daily abuse in 20-24% [44]. A recent Australian study reported that 41% of opioid substitution clients were ‘AUDIT positive', indicating excessive alcohol use [45], but only half of them believed they drank too much.

In a large German study [46] in 1,685 heroin users and patients on opioid maintenance treatment (with methadone or codeine), 28% of participants consumed more than 40 g alcohol/day. The average alcohol consumption was significantly higher in heroin users than in methadone-treated patients. Predictors of alcohol use were male sex, daily cannabis and benzodiazepine consumption, and longer duration of drug use. Meta-analyses of US clinical trials found AUD in 38 and 45% of patients seeking treatment for opioid or stimulant use, respectively [47, 48].

AUD are associated with an increased risk of fatal overdose [49](see below), hepatotoxicity (especially in hepatitis-positive individuals) [50], interactions with methadone [51, 52] and negative clinical outcome [53, 54]. Hepatitis infections are very common in opioid users [55]. Prevalence estimates of hepatitis C range from 64 to 100% in many cohorts [56, 57, 58, 59, 60, 61, 62]. Chronic alcohol intake is an important risk factor for progression to hepatic cirrhosis [50].

Alcohol dependence and AUD are usually considered to be risk factors for compliance and predictors for a negative treatment outcome, although this has not been reported in all studies [63]. According to recent data, substance use, including alcohol-related problems, may be attributed to perceived stress [64]. Stress management may therefore be a suitable approach to minimize the risk of alcohol intake.

Most patients with alcohol abuse show noncompliance and nonadherence to treatment [65]. Inadequate opioid dosage during maintenance therapy may explain alcohol or other drug use in some patients. Ottomanelli [7] found that non-alcohol-abusing clients request higher doses of opioids.

Sebanjo et al. [42] evaluated the effects of excessive alcohol consumption on the health-related quality of life in patients receiving methadone treatment and found significant impairments in various domains, including social functioning.

Genetic variables have hardly been studied to date. Wang et al. [66] reported that a kappa-opioid receptor 1 gene polymorphism is associated with alcohol use, among other things.

There is broad consensus that opioid-dependent patients have a substantial risk of premature death, mostly associated with fatal overdose or polysubstance intoxications [67]. Long-term studies in opioid-dependent individuals indicate a low abstinence and high mortality rate [67, 68, 69, 70]. The all-cause mortality rate was estimated at 2.09 per 100 person-years [71]. Problem drug users were found by the European Monitoring Centre for Drugs and Drug Addiction [1] to have a 10- to 20-fold higher mortality risk than their peers. Maintenance treatment significantly reduces mortality rates compared with untreated heroin dependence [71].

AUD are associated with an increased risk of fatal overdose in opioid dependence [72] and numerous studies have identified alcohol abuse or dependence as a risk factor for mortality in opioid-dependent patients [73]. Degenhardt et al. [74] recently published a comprehensive study on causes of death in the years 1995-2005 in a large Australian cohort (n = 43,789) of opioid-dependent people. Of the 3,685 deaths, the majority (52%) were drug related and were mostly accidental opioid deaths; 3% were alcohol related and 7% were liver related (3% chronic liver disease and 3% viral hepatitis). The standard mortality ratio for the most common causes of death for alcohol-related disorders was 5.4%. Because both heavy and dependent alcohol use have been described in older opioid-dependent people [75], screening for and treatment of hazardous alcohol use is recommended for this group [74]. Another recent large (n = 68,066) retrospective cohort study also found a high mortality rate: drug- or alcohol-induced deaths accounted for 23% of the cases [76].

A number of psychosocial approaches and therapies with the goal of abstinence from opioids have proven efficacy in opioid dependence, but overall abstinence rates are rather low and rarely exceed 20% [77]. Maintenance treatment with full or partial opioid agonists reduces opioid consumption, criminal behavior and psychosocial and medical morbidity, including rates of HIV and hepatitis B virus infections, as indicated by many studies and meta-analyses [78, 79, 80, 81, 82, 83, 84]. The efficacy of buprenorphine and its combination with naloxone in reducing substance use and improving social and clinical functioning in opioid-dependent individuals has been demonstrated by numerous studies [84, 85, 86, 87] and both methadone and buprenorphine are recommended as effective, first-line medications in the treatment of opioid dependence by relevant treatment guidelines [5, 88, 89, 90] and reviews [78, 80, 82, 83, 85, 91].

The interaction of opioid dependence, maintenance therapy and alcohol consumption is complex (table 2). Addressing opioid dependence adequately by increasing the dose of maintenance treatment does not automatically decrease alcohol consumption [92, 93]. For example, short-term methadone maintenance therapy was reported to decrease alcohol consumption and long-term treatment to increase it as indicated by the data reviewed by Caputo et al. [94]. Hser et al. [95] reported that alcohol consumption increases whenever narcotic use decreases, and Anglin et al. [96] also claimed that alcohol and heroin use are inversely related. Caputo et al. [94] reported a significant reduction in daily alcohol intake in methadone-treated, nonalcoholic, opioid-dependent patients compared to nonmethadone-dependent clients. In an 18-month longitudinal cohort study on exposure to treatment for heroin addiction, Schifano et al. [97] found that heroin, benzodiazepine and polydrug abuse decreased over time, but alcohol (and cannabis) use did not. Fishman et al. [98] reported on a female patient with an addiction to prescription opioids and comorbid depression and alcohol dependence who benefited from treatment with buprenorphine.

Table 2

AUD in opioid dependence

AUD in opioid dependence
AUD in opioid dependence

In some European countries heroin is used to treat opioid dependence. A secondary analysis of a randomized German study comparing heroin treatment with methadone treatment [99] found a significant reduction in carbohydrate-deficient transferrin values in both groups, but a reduction in the ASI alcohol subscore only in the heroin group. Interestingly, this result was discussed with respect to setting effects: daily dispensing of heroin may have prevented this group from consuming more alcohol. A reduction in the ASI alcohol subscore was also reported in a large German naturalistic follow-up study of 1,694 patients in opioid maintenance treatment for 6-7 years; the study also found a higher rate of ‘critical' alcohol consumption in methadone patients (36-50%) than in buprenorphine patients (24-27%) over time [100].

Some studies suggest that opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence. In a 12-month open randomized study, the effects of methadone (80, 120, 160 and 200 mg) and buprenorphine (8, 16, 24 and 32 mg) on opioid and alcohol consumption (as measured by ASI scores) were assessed in 218 patients [101]. Both treatments decreased opioid and alcohol consumption, but the only statistically significant finding was that the highest buprenorphine dose suppressed alcohol craving and intake more than the highest methadone dose.

Srivastava et al. [8] performed a systematic review of 15 studies on the effects of methadone treatment on alcohol consumption. Three studies indicated an increase in alcohol use during treatment and 3 indicated a decrease; 9 studies did not report any change. Apparently there is no clear pattern concerning the effects of opioid maintenance therapy on alcohol consumption.

The US Substance Abuse and Mental Health Services Administration (SAMHSA) concluded the following in their clinical guidelines for the use of buprenorphine in the treatment of opioid addiction [102]: ‘Pharmacotherapy with buprenorphine for opioid addiction will not necessarily have a beneficial effect on an individual's use of other drugs. It is essential that patients be referred to treatment of addiction to other types of drugs when indicated. In addition, care must be exercised in the prescribing of buprenorphine for patients who abuse alcohol… because of the documented potential for fatal interactions.' This may be true for all drugs used for opioid maintenance treatment.

The issue of AUD in opioid-dependent patients has been widely neglected. A 1-year follow-up study found improvements in alcohol consumption in a minority of patients only [6]. Because many patients underestimate the risks associated with their alcohol consumption, alcohol use should be regularly assessed and brief alcohol interventions performed when necessary [45].

Only a few systematic studies have been published on AUD in opioid dependence [103, 104]. When preparing their systematic Cochrane review on this topic, Klimas et al. [105, 106] identified 4 studies with 594 participants. The studies measured 6 different psychosocial interventions grouped into 4 comparisons: cognitive-behavioral coping skills training versus 12-step facilitation (n = 41) [107], brief intervention versus treatment as usual (n = 110) [108], hepatitis health promotion versus motivational interviewing (n = 256) [65], and brief motivational intervention versus an assessment-only group (n = 187) [109]. The authors were not able to perform a meta-analysis of all the studies because of clinical and methodological differences between them. Most of the comparisons were not statistically significant, except for decreased alcohol use at 3 and 9 months with the control intervention in the studyby Feldman et al. [108]. Also, at 6 months participants receiving brief motivational intervention were significantly more likely than the control group to have reduced their alcohol use by 7 or more days in the past 30 days [109]. Similar to previous reviews [103, 104], the Cochrane review was unable to recommend using or ceasing psychosocial interventions for alcohol use problems in illicit drug users: ‘Given the high rates of co-occurrence of alcohol and drug problems, integration of alcohol- and drug-orientated interventions appears a logical action, but in light of this review remains without an evidence base' [105].

The same group is currently conducting a study to determine the feasibility of a complex intervention for problem alcohol use among problem drug users [110]. A new and interesting study has been performed on this topic: Darker et al. [111] studied the effectiveness of brief interventions to reduce hazardous and harmful alcohol consumption in opiate-dependent methadone-maintained patients and excluded alcohol-dependent patients. The study assessed the change in scores on the Alcohol Use Disorders Identification Test (AUDIT-C) from baseline to the 3-month follow-up in 160 patients (15 were lost to follow-up). This implementation study found a clear reduction in alcohol consumption after treatment. Brief interventions are frequently used in alcohol treatment [112], but not in treatment for addiction to illicit drugs.

So-called anti-craving drugs such as the opioid antagonists naltrexone and nalmefene [28, 113] and the putative glutamate modulator acamprosate [114] may help to reduce alcohol consumption. The first two substances precipitate opioid withdrawal and are contraindicated in opioid-dependent patients, while acamprosate has not been tested in opioid users. The anticraving drug acamprosate has no contraindication in opioid dependence and no pharmacological interactions with opioids.

The overall evidence for disulfiram as an effective medication in alcoholism is limited [115, 116] and basically restricted to supervised treatment settings. Since opioid maintenance therapy may be considered as such a supervised setting, disulfiram may fit in here. Disulfiram was also studied as a possible medication for the treatment of cocaine dependence in methadone-stabilized patients [117] and positive results were reported in patients maintained with buprenorphine [118], but disulfiram may also work in those with current alcohol use disorder [107]. Unlike cocaine and possibly methadone, disulfiram was not found to prolong the QTc interval [119].

Hepatotoxicity must be considered when addressing AUD in opioid dependence. While methadone has been considered to be safe, clinical reports of liver injury in patients with hepatitis have raised concerns about the hepatotoxicity of buprenorphine and the buprenorphine/naloxone combination [120, 121, 122, 123, 124, 125, 126]. Hervè et al. [127] reported on 7 cases of acute cytolytic hepatitis due to buprenorphine. Five of 7 patients presented with acute icteric hepatitis without abdominal pain or fever or evidence for liver failure; after reexposure some of the patients remained on a lower dose without further evidence of liver injury.

More systematic studies found little evidence for buprenorphine hepatotoxicity. Bogenschutz et al. [128] studied 152 patients randomized to 2 weeks' detoxification with buprenorphine-naloxone or 12 weeks' treatment with buprenorphine-naloxone and obtained at least one set of transaminase measurements for 111 patients. At least one elevated aspartate aminotransferase value was found in 8 of the 60 buprenorphine/naloxone patients and 12 of the 51 detoxification patients. Hepatitis C status was significantly associated with transaminase abnormalities. Taken together, this exploratory study found no evidence for hepatotoxicity of buprenorphine.

Saxon et al. [129] performed a controlled study of 1,269 opioid-dependent, treatment-seeking patients randomized to either buprenorphine or methadone and followed them for 32 weeks. A total of 731 participants met ‘evaluable' criteria, defined as completing 24 weeks of medication and providing at least 4 blood samples. Changes in transaminase levels did not differ by medication condition. The study found no evidence that buprenorphine is associated with liver injury. A recent phase IV study also found no evidence for liver toxicity associated with buprenorphine [31]. Data from a large study comparing short- and long-term effects of buprenorphine on liver function indicate that hepatitis C seroconversion was strongly associated with ALT elevations [130].

Methadone, but not buprenorphine, was found to have some rare cardiotoxic effects, including causing torsades de pointes [90]. The possibility of such side effects must be kept in mind when treating alcohol-dependent patients with possible cardiomyopathy. ECG controls are recommended.

The current data indicate that AUD are a significant problem in about a third of the patients in opioid maintenance therapy and have a significant impact on morbidity and mortality. According to most studies, opioid maintenance therapy does not change alcohol consumption, at least not in the majority of cases, but dose adjustments may help to reduce the risk of substance use, including alcohol. A simple diagnostic approach such as the use of a breathalyzer may be useful to detect affected patients. More research is needed on psychosocial strategies for use in patients with alcohol abuse. It is already difficult to define effective psychosocial interventions for the treatment of opioid use [131, 132], and therefore even more difficult to suggest evidence-based treatments for comorbid alcoholic patients. Brief interventions and treatment modifications, such as more regular visits or a more intense approach without prolonged periods at home, may be helpful. In more severe cases, selective (alcohol) detoxification may be considered.

The author thanks Jacquie Klesing, Board-Certified Editor in the Life Sciences (ELS), for editing assistance with the manuscript.

No funding was received for the preparation of this paper. For the past 5 years, the author has worked as a consultant or received research or travel grants from Sanofi Aventis, Reckitt Benckiser, Lundbeck, Prempharm and Phoenux.

1.
EMCDDA: Mortality Related to Drug Use in Europe: Public Health Implications. Lisbon, EMCDDA, 2011.
2.
Mathers BM, Degenhardt L, Phillips B, Wiessing L, Hickman M, Strathdee SA, Wodak A, Panda S, Tyndall M, Toufik A, Mattick RP: Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review. Lancet 2008;372:1733-1745.
[PubMed]
3.
United Nations Office on Drugs and Crime: 2006 World Drug Report. Vienna, UNODC, 2006.
4.
Kessler RC, Avenevoli S, Costello EJ, Georgiades K, Green JG, Gruber MJ, He JP, Koretz D, McLaughlin KA, Petukhova M, Sampson NA, Zaslavsky AM, Merikangas KR: Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry 2012;69:372-380.
[PubMed]
5.
Kleber HD, Weiss RD, Anton RF Jr, George TP, Greenfield SF, Kosten TR, O'Brien CP, Rounsaville BJ, Strain EC, Ziedonis DM, Hennessy G, Connery HS, McIntyre JS, Charles SC, Anzia DJ, Cook IA, Finnerty MT, Johnson BR, Nininger JE, Summergrad P, Woods SM, Yager J, Pyles R, Cross CD, Peele R, Shemo JP, Lurie L, Walker RD, Barnovitz MA, Gray SH, Saxena S, Tonnu T, Kunkle R, Albert AB, Fochtmann LJ, Hart C, Regier D: Treatment of patients with substance use disorders, second edition. American Psychiatric Association. Am J Psychiatry 2007;164:5-123.
[PubMed]
6.
Gossop M, Marsden J, Stewart D, Rolfe A: Patterns of drinking and drinking outcomes among drug misusers. 1-year follow-up results. J Subst Abuse Treat 2000;19:45-50.
[PubMed]
7.
Ottomanelli G: Methadone patients and alcohol abuse. J Subst Abuse Treat 1999;16:113-121.
[PubMed]
8.
Srivastava A, Kahan M, Ross S: The effect of methadone maintenance treatment on alcohol consumption: a systematic review. J Subst Abuse Treat 2008;34:215-223.
[PubMed]
9.
Koob GF, Le Moal M: Neurobiology of Addiction. Amsterdam, Academic Press, 2006.
10.
Spanagel R: Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev 2009;89:649-705.
[PubMed]
11.
Spanagel R, Vengeliene V: New pharmacological treatment strategies for relapse prevention. Curr Top Behav Neurosci 2013;13:583-609.
[PubMed]
12.
Dai X, Thavundayil J, Gianoulakis C: Differences in the peripheral levels of beta-endorphin in response to alcohol and stress as a function of alcohol dependence and family history of alcoholism. Alcohol Clin Exp Res 2005;29:1965-1975.
[PubMed]
13.
Koob GF, Roberts AJ, Kieffer BL, Heyser CJ, Katner SN, Ciccocioppo R, Weiss F: Animal models of motivation for drinking in rodents with a focus on opioid receptor neuropharmacology. Recent Dev Alcohol 2003;16:263-281.
[PubMed]
14.
Marinelli PW, Bai L, Quirion R, Gianoulakis C: A microdialysis profile of Met-enkephalin release in the rat nucleus accumbens following alcohol administration. Alcohol Clin Exp Res 2005;29:1821-1828.
[PubMed]
15.
Marinelli PW, Lam M, Bai L, Quirion R, Gianoulakis C: A microdialysis profile of dynorphin A(1-8) release in the rat nucleus accumbens following alcohol administration. Alcohol Clin Exp Res 2006;30:982-990.
[PubMed]
16.
Marinelli PW, Quirion R, Gianoulakis C: An in vivo profile of beta-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol. Neuroscience 2004;127:777-784.
[PubMed]
17.
Barson JR, Carr AJ, Soun JE, Sobhani NC, Rada P, Leibowitz SF, Hoebel BG: Opioids in the hypothalamic paraventricular nucleus stimulate ethanol intake. Alcohol Clin Exp Res 2010;34:214-222.
[PubMed]
18.
Herz A: Endogenous opioid systems and alcohol addiction. Psychopharmacology (Berl) 1997;129:99-111.
[PubMed]
19.
Hubbell CL, Abelson ML, Burkhardt CA, Herlands SE, Reid LD: Constant infusions of morphine and intakes of sweetened ethanol solution among rats. Alcohol 1988;5:409-415.
[PubMed]
20.
Hubbell CL, Czirr SA, Hunter GA, Beaman CM, LeCann NC, Reid LD: Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administrations. Alcohol 1986;3:39-54.
[PubMed]
21.
Oswald LM, Wand GS: Opioids and alcoholism. Physiol Behav 2004;81:339-358.
[PubMed]
22.
Goeders NE, Lane JD, Smith JE: Self-administration of methionine enkephalin into the nucleus accumbens. Pharmacol Biochem Behav 1984;20:451-455.
[PubMed]
23.
Jarjour S, Bai L, Gianoulakis C: Effect of acute ethanol administration on the release of opioid peptides from the midbrain including the ventral tegmental area. Alcohol Clin Exp Res 2009;33:1033-1043.
[PubMed]
24.
Reid LD: Endogenous opioids and alcohol dependence: opioid alkaloids and the propensity to drink alcoholic beverages. Alcohol 1996;13:5-11.
[PubMed]
25.
Belluzzi JD, Stein L: Enkephalin may mediate euphoria and drive-reduction reward. Nature 1977;266:556-558.
[PubMed]
26.
Gianoulakis C: Endogenous opioids and addiction to alcohol and other drugs of abuse. Curr Top Med Chem 2004;4:39-50.
[PubMed]
27.
Schwantes-An T-HL, Zhang J, Chen L-S, Hartz SM, Culverhouse RC, Chen X, Coon H, Frank J, Kamens HM, Konte B, Kovanen L, Latvala A, et al: Collaborative meta-analysis demonstrates modest association of the OPRM1 variant rs1799971 (A118G) with non-specific liability to substance dependence. Mol Psychiatry, submitted.
28.
Rosner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M: Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010;12:CD001867.
[PubMed]
29.
Chamorro AJ, Marcos M, Miron-Canelo JA, Pastor I, Gonzalez-Sarmiento R, Laso FJ: Association of micro-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis. Addict Biol 2012;17:505-512.
[PubMed]
30.
Anderson P, Gual A, Colom J: Alcohol and Primary Care: Guidelines on Identification and Brief Interventions. Barcelona, Department of Health of the Government of Catalonia, 2005.
31.
Soyka M, Bachmund M, Schmidt P, Apelt S: Buprenorphine-naloxone treatment in opioid dependence and risk of liver enzyme elevation - results from a 12-month observational study. Am J Addict 2014;23:563-569.
[PubMed]
32.
Teplin D, Raz B, Daiter J, Varenbut M, Plater-Zyberk C: Screening for alcohol use patterns among methadone maintenance patients. Am J Drug Alcohol Abuse 2007;33:179-183.
[PubMed]
33.
Dahl H, Voltaire Carlsson A, Hillgren K, Helander A: Urinary ethyl glucuronide and ethyl sulfate testing for detection of recent drinking in an outpatient treatment program for alcohol and drug dependence. Alcohol Alcohol 2011;46:278-282.
[PubMed]
34.
Wurst FM, Dursteler-MacFarland KM, Auwaerter V, Ergovic S, Thon N, Yegles M, Halter C, Weinmann W, Wiesbeck GA: Assessment of alcohol use among methadone maintenance patients by direct ethanol metabolites and self-reports. Alcohol Clin Exp Res 2008;32:1552-1557.
[PubMed]
35.
Wurst FM, Haber PS, Wiesbeck G, Watson B, Wallace C, Whitfield JB, Halter C, Weinmann W, Conigrave KM: Assessment of alcohol consumption among hepatitis C-positive people receiving opioid maintenance treatment using direct ethanol metabolites and self-report: a pilot study. Addict Biol 2008;13:416-422.
[PubMed]
36.
Stenbacka M, Beck O, Leifman A, Romelsjo A, Helander A: Problem drinking in relation to treatment outcome among opiate addicts in methadone maintenance treatment. Drug Alcohol Rev 2007;26:55-63.
[PubMed]
37.
Gsellhofer B, Kuefner H, Vogt M, Weller D: European Addiction Severity. Index-EuropASI. Manual for Training and Execution. Stuttgart, Scheider Verlag, 1999.
38.
Babor TF, Grant M: From clinical research to secondary prevention international collaboration in the development of the Alcohol Use Disorders Identification Test (AUDIT). Alcohol Health Res World 1989;13:371-374.
39.
Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG: AUDIT. The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Health Care, ed 2. Geneva, World Health Organization, 2001.
40.
Bennett GA, Edwards S, Bailey J: Helping methadone patients who drink excessively to drink less: short-term outcome of a pilot motivational intervention. J Subst Use 2002;7:191-197.
41.
Rittmannsberger H, Silberbauer C, Lehner R, Ruschak M: Alcohol consumption during methadone maintenance treatment. Eur Addict Res 2000;6:2-7.
[PubMed]
42.
Sebanjo R, Wolff K, Marshall J: Excessive alcohol consumption is associated with reduced quality of life among methadone patients. Addiction 2006;102:257-263.
[PubMed]
43.
Ryder N, Cullen W, Barry J, Bury G, Keenan E, Smyth BP: Prevalence of problem alcohol use among patients attending primary care for methadone treatment. BMC Fam Pract 2009;10:42.
[PubMed]
44.
Dobler-Mikola A, Hattenschwiler J, Meili D, Beck T, Boni E, Modestin J: Patterns of heroin, cocaine, and alcohol abuse during long-term methadone maintenance treatment. J Subst Abuse Treat 2005;29:259-265.
[PubMed]
45.
Islam MM, Day CA, Conigrave KM, Topp L: Self-perceived problem with alcohol use among opioid substitution treatment clients. Addict Behav 2013;38:2018-2021.
[PubMed]
46.
Backmund M, Schutz CG, Meyer K, Eichenlaub D, Soyka M: Alcohol consumption in heroin users, methadone-substituted and codeine-substituted patients - frequency and correlates of use. Eur Addict Res 2003;9:45-50.
[PubMed]
47.
Hartzler B, Donovan DM, Huang Z: Comparison of opiate-primary treatment seekers with and without alcohol use disorder. J Subst Abuse Treat 2010;39:114-123.
[PubMed]
48.
Hartzler B, Donovan DM, Huang Z: Rates and influences of alcohol use disorder comorbidity among primary stimulant misusing treatment-seekers: Meta-analytic findings across eight NIDA CTN trials. Am J Drug Alcohol Abuse 2011;37:460-471.
[PubMed]
49.
White J, Irvine R: Mechanisms of fatal opioid ‘overdose': a review. Addiction 1996;91:1765-1772.
50.
Ostapowicz G, Watson KJ, Locarnini SA, Desmond PV: Role of alcohol in the progression of liver disease caused by hepatitis c virus infection. Hepatology 1998;27:1730-1735.
[PubMed]
51.
Bickel WK, Amass L: The relationship of mean daily blood alcohol levels to admission MAST, clinic absenteeism and depression in alcoholic methadone patients. Drug Alcohol Depend 1993;32:113-118.
[PubMed]
52.
Kreek MJ: Metabolic interactions between opiates and alcohol. Ann NY Acad Sci 1981;362:36-49.
[PubMed]
53.
Joseph H, Appel P: Alcoholism and methadone treatment: consequences for the patient and program. Am J Drug Alcohol Abuse 1985;11:37-53.
[PubMed]
54.
Ferri M, Finlayson AJ, Wang L, Martin PR: Predictive factors for relapse in patients on buprenorphine maintenance. Am J Addict 2014;23:62-67.
[PubMed]
55.
Smyth BP, Keenan E, O'Connor JJ: Bloodborne viral infection in Irish injecting drug users. Addiction 1998;93:1649-1656.
[PubMed]
56.
Abraham HD, Degli-Esposti S, Marino L: Seroprevalence of hepatitis C in a sample of middle class substance abusers. J Addict Dis 1999;18:77-87.
[PubMed]
57.
Diaz T, Des Jarlais DC, Vlahov D, Perlis TE, Edwards V, Friedman SR, Rockwell R, Hoover D, Williams IT, Monterroso ER: Factors associated with prevalent hepatitis C: differences among young adult injection drug users in lower and upper Manhattan, New York City. Am J Public Health 2001;91:23-30.
[PubMed]
58.
Murrill CS, Weeks H, Castrucci BC, Weinstock HS, Bell BP, Spruill C, Gwinn M: Age-specific seroprevalence of HIV, hepatitis B virus, and hepatitis C virus infection among injection drug users admitted to drug treatment in 6 US cities. Am J Public Health 2002;92:385-387.
[PubMed]
59.
Novick DM, Kreek MJ: Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients. Addiction 2008;103:905-918.
[PubMed]
60.
Patrick DM, Tyndall MW, Cornelisse PG, Li K, Sherlock CH, Rekart ML, Strathdee SA, Currie SL, Schechter MT, O'Shaughnessy MV: Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection. CMAJ 2001;165:889-895.
[PubMed]
61.
Rosenblum A, Nuttbrock L, McQuistion HL, Magura S, Joseph H: Hepatitis C and substance use in a sample of homeless people in New York City. J Addict Dis 2001;20:15-25.
[PubMed]
62.
Wittchen HU, Buhringer G, Rehm JT, Soyka M, Trader A, Mark K, Trautmann S: Der Verlauf und Ausgang von Substitutionspatienten unter den aktuellen Bedingungen der deutschen Substitutionsversorgung nach 6 Jahren. Suchtmed 2011;13:232-246.
63.
Potter JS, Marino EN, Hillhouse MP, Nielsen S, Wiest K, Canamar CP, Martin JA, Ang A, Baker R, Saxon AJ, Ling W: Buprenorphine/naloxone and methadone maintenance treatment outcomes for opioid analgesic, heroin, and combined users: findings from Starting Treatment with Agonist Replacement Therapies (START). J Stud Alcohol Drugs 2013;74:605-613.
[PubMed]
64.
Moitra E, Anderson BJ, Stein MD: Perceived stress and substance use in methadone-maintained smokers. Drug Alcohol Depend 2013;133:785-788.
[PubMed]
65.
Nyamathi A, Shoptaw S, Cohen A, Greengold B, Nyamathi K, Marfisee M, de Castro V, Khalilifard F, George D, Leake B: Effect of motivational interviewing on reduction of alcohol use. Drug Alcohol Depend 2010;107:23-30.
[PubMed]
66.
Wang SC, Tsou HH, Chung RH, Chang YS, Fang CP, Chen CH, Ho IK, Kuo HW, Liu SC, Shih YH, Wu HY, Huang BH, Lin KM, Chen AC, Hsiao CF, Liu YL: The association of genetic polymorphisms in the kappa-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance. J Clin Psychopharmacol 2014;34:205-211.
[PubMed]
67.
Hser YI, Anglin D, Powers K: A 24-year follow-up of California narcotics addicts. Arch Gen Psychiatry 1993;50:577-584.
[PubMed]
68.
Bargagli AM, Hickman M, Davoli M, Perucci CA, Schifano P, Buster M, Brugal T, Vicente J: Drug-related mortality and its impact on adult mortality in eight European countries. Eur J Public Health 2006;16:198-202.
[PubMed]
69.
Bjornaas MA, Bekken AS, Ojlert A, Haldorsen T, Jacobsen D, Rostrup M, Ekeberg O: A 20-year prospective study of mortality and causes of death among hospitalized opioid addicts in Oslo. BMC Psychiatry 2008;8:8.
[PubMed]
70.
Termorshuizen F, Krol A, Prins M, van Ameijden EJ: Long-term outcome of chronic drug use: the Amsterdam cohort study among drug users. Am J Epidemiol 2005;161:271-279.
[PubMed]
71.
Degenhardt L, Bucello C, Mathers B, Briegleb C, Ali H, Hickman M, McLaren J: Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies. Addiction 2011;106:32-51.
[PubMed]
72.
Darke S, Zador D: Fatal heroin ‘overdose': a review. Addiction 1996;91:1765-1772.
[PubMed]
73.
Huang CL, Lee CW: Factors associated with mortality among heroin users after seeking treatment with methadone: a population-based cohort study in Taiwan. J Subst Abuse Treat 2013;44:295-300.
[PubMed]
74.
Degenhardt L, Larney S, Randall D, Burns L, Hall W: Causes of death in a cohort treated for opioid dependence between 1985 and 2005. Addiction 2014;109:90-99.
[PubMed]
75.
Shand FL, Degenhardt L, Slade T, Nelson EC: Sex differences amongst dependent heroin users: histories, clinical characteristics and predictors of other substance dependence. Addict Behav 2011;36:27-36.
[PubMed]
76.
Veldhuizen S, Callaghan RC: Cause-specific mortality among people previously hospitalized with opioid-related conditions: a retrospective cohort study. Ann Epidemiol 2014;24:620-624.
[PubMed]
77.
Berglund M, Thelander S, Jonsson E: Treating Alcohol and Drug Abuse - An Evidence Based Review. Weinheim, Wiley-VCH, 2003.
78.
Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP: An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. J Subst Abuse Treat 2005;28:321-329.
[PubMed]
79.
Bukten A, Skurtveit S, Gossop M, Waal H, Stangeland P, Havnes I, Clausen T: Engagement with opioid maintenance treatment and reductions in crime: a longitudinal national cohort study. Addiction 2012;107:393-399.
[PubMed]
80.
Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, Fry-Smith A, Day E, Lintzeris N, Roberts T, Burls A, Taylor RS: Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. Health Technol Assess 2007;11:1-171, iii-iv.
[PubMed]
81.
Maremmani I, Gerra G: Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment. Am J Addict 2010;19:557-568.
[PubMed]
82.
Mattick RP, Breen C, Kimber J, Davoli M: Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009;3:CD002209.
[PubMed]
83.
Mattick RP, Kimber J, Breen C, Davoli M: Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2008;2:CD002207.
[PubMed]
84.
Soyka M, Zingg C, Koller G, Kuefner H: Retention rate and substance use in methadone and buprenorphine maintenance therapy and predictors of outcome: results from a randomized study. Int J Neuropsychopharmacol 2008;11:641-653.
[PubMed]
85.
Orman JS, Keating GM: Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence. Drugs 2009;69:577-607.
[PubMed]
86.
Kakko J, Svanborg KD, Kreek MJ, Heilig M: 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet 2003;361:662-668.
[PubMed]
87.
Kamien JB, Branstetter SA, Amass L: Buprenorphine-naloxone versus methadone maintenance therapy: a randomised double-blind trial with opioid-dependent patients. Heroin Addict Relat Clin Probl 2008;10:5-18.
88.
National Institute for Health and Clinical Excellence: Drug Misuse: Opioid Detoxification. London, NICE, 2007.
[PubMed]
89.
New South Wales Department of Health: Opioid Treatment Program: Clinical Guidelines for Methadone and Buprenorphine Treatment. Sydney, NSW Government, 2006.
90.
Soyka M, Kranzler HR, van den Brink W, Krystal J, Moller HJ, Kasper S: The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of substance use and related disorders. Part 2: opioid dependence. World J Biol Psychiatry 2011;12:160-187.
[PubMed]
91.
Mammen K, Bell J: The clinical efficacy and abuse potential of combination buprenorphine-naloxone in the treatment of opioid dependence. Expert Opin Pharmacother 2009;10:2537-2544.
[PubMed]
92.
Fairbank JA, Dunteman GH, Condelli WS: Do methadone patients substitute other drugs for heroin? Predicting substance use at 1-year follow-up. Am J Drug Alcohol Abuse 1993;19:465-474.
[PubMed]
93.
Gossop M, Marsden J, Stewart D, Treacy S: Change and stability of change after treatment of drug misuse: 2-year outcomes from the National Treatment Outcome Research Study (UK). Addict Behav 2002;27:155-166.
[PubMed]
94.
Caputo F, Addolorato G, Domenicali M, Mosti A, Viaggi M, Trevisani F, Gasbarrini G, Bernardi M, Stefanini GF: Short-term methadone administration reduces alcohol consumption in non-alcoholic heroin addicts. Alcohol Alcohol 2002;37:164-168.
[PubMed]
95.
Hser YI, Anglin MD, Powers K: Longitudinal patterns of alcohol use by narcotics addicts. Recent Dev Alcohol 1990;8:145-171.
[PubMed]
96.
Anglin MD, Almog IJ, Fisher DG, Peters KR: Alcohol use by heroin addicts: evidence for an inverse relationship. A study of methadone maintenance and drug-free treatment samples. Am J Drug Alcohol Abuse 1989;15:191-207.
[PubMed]
97.
Schifano F, Martinotti G, Cunniff A, Reissner V, Scherbaum N, Ghodse H: Impact of an 18-month, NHS-based, treatment exposure for heroin dependence: results from the London Area Treat 2000 study. Am J Addict 2012;21:268-273.
[PubMed]
98.
Fishman MJ, Wu LT, Woody GE: Buprenorphine for prescription opioid addiction in a patient with depression and alcohol dependence. Am J Psychiatry 2011;168:675-679.
[PubMed]
99.
Haasen C, Eiroa-Orosa FJ, Verthein U, Soyka M, Dilg C, Schäfer I, Reimer J: Effects of heroin-assisted treatment on alcohol consumption: findings of the German randomized controlled trial. Alcohol 2009;43:259-264.
[PubMed]
100.
Wittchen HU, Buhringer G, Rehm JT, Klotsche J: Die Stabilität der 6-Jahres-Langzeitbefunde in Premos: Ein Vergleich mit den 7-Jahresdaten ein Jahr später. Suchtmed 2011;13:269-271.
101.
Nava F, Manzato E, Leonardi C, Lucchini A: Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: preliminary results of an open randomized study. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1867-1872.
[PubMed]
102.
Center for Substance Abuse Treatment (US): Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) series 40. DHHS publication No. (SMA) 04-3939. Rockville, Substance Abuse and Mental Health Services Administration, 2004.
[PubMed]
103.
Arias AJ, Kranzler HR: Treatment of co-occurring alcohol and other drug use disorders. Alcohol Res Health 2008;31:155-167.
[PubMed]
104.
Bickel WK, Marion I, Lowinson JH: The treatment of alcoholic methadone patients: a review. J Subst Abuse Treat 1987;4:15-19.
[PubMed]
105.
Klimas J, Field CA, Cullen W, O'Gorman CS, Glynn LG, Keenan E, Saunders J, Bury G, Dunne C: Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users: Cochrane review. Syst Rev 2013;2:3.
[PubMed]
106.
Klimas J, Field CA, Cullen W, O'Gorman CS, Glynn LG, Keenan E, Saunders J, Bury G, Dunne C: Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Cochrane Database Syst Rev 2012;11:CD009269.
[PubMed]
107.
Carroll KM, Nich C, Ball SA, McCance E, Rounsavile BJ: Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction 1998;93:713-727.
[PubMed]
108.
Feldman N, Chatton A, Khan R, Khazaal Y, Zullino D: Alcohol-related brief intervention in patients treated for opiate or cocaine dependence: a randomized controlled study. Subst Abuse Treat Prev Policy 2011;6:22.
[PubMed]
109.
Stein MD, Charuvastra A, Maksad J, Anderson BJ: A randomized trial of a brief alcohol intervention for needle exchangers (BRAINE). Addiction 2002;97:691-700.
[PubMed]
110.
Klimas J, Anderson R, Bourke M, Bury G, Field CA, Kaner E, Keane R, Keenan E, Meagher D, Murphy B, O'Gorman CS, O'Toole TP, Saunders J, Smyth BP, Dunne C, Cullen W: Psychosocial interventions for alcohol use among problem drug users: protocol for a feasibility study in primary care. JMIR Res Protoc 2013;2:e26.
[PubMed]
111.
Darker CD, Sweeney BP, El Hassan HO, Smyth BP, Ivers JH, Barry JM: Brief interventions are effective in reducing alcohol consumption in opiate-dependent methadone-maintained patients: results from an implementation study. Drug Alcohol Rev 2012;31:348-356.
[PubMed]
112.
Babor TF, Higgins-Biddle JC: Brief intervention for hazardous and harmful drinking. A manual for use in primary care. Geneva, World Health Organization, 2001.
113.
Soyka M: Nalmefene for the treatment of alcohol dependence: a current update. Int J Neuropsychopharmacol 2014;17:675-684.
[PubMed]
114.
Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M: Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010;9:CD004332.
[PubMed]
115.
Carroll KM, Nich C, Shi JM, Eagan D, Ball SA: Efficacy of disulfiram and twelve step facilitation in cocaine-dependent individuals maintained on methadone: a randomized placebo-controlled trial. Drug Alcohol Depend 2012;126:224-231.
[PubMed]
116.
Jorgensen CH, Pedersen B, Tonnesen H: The efficacy of disulfiram for the treatment of alcohol use disorder. Alcohol Clin Exp Res 2011;35:1749-1758.
[PubMed]
117.
Oliveto A, Poling J, Mancino MJ, Feldman Z, Cubells JF, Pruzinsky R, Gonsai K, Cargile C, Sofuoglu M, Chopra MP, Gonzalez-Haddad G, Carroll KM, Kosten TR: Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients. Drug Alcohol Depend 2011;113:184-191.
[PubMed]
118.
Schottenfeld RS, Chawarski MC, Cubells JF, George TP, Lappalainen J, Kosten TR: Randomized clinical trial of disulfiram for cocaine dependence or abuse during buprenorphine treatment. Drug Alcohol Depend 2014;136:36-42.
[PubMed]
119.
Atkinson TS, Sanders N, Mancino M, Oliveto A: Effects of disulfiram on QTc interval in non-opioid-dependent and methadone-treated cocaine-dependent patients. J Addict Med 2013;7:243-248.
[PubMed]
120.
Berson A, Fau D, Fornacciari R, Degove-Goddard P, Sutton A, Descatoire V, Haouzi D, Letteron P, Moreau A, Feldmann G, Pessayre D: Mechanisms for experimental buprenorphine hepatotoxicity: major role of mitochondrial dysfunction versus metabolic activation. J Hepatol 2001;34:261-269.
[PubMed]
121.
Berson A, Gervais A, Cazals D, Boyer N, Durand F, Bernuau J, Marcellin P, Degott C, Valla D, Pessayre D: Hepatitis after intravenous buprenorphine misuse in heroin addicts. J Hepatol 2001;34:346-350.
[PubMed]
122.
Bruce RD, Altice FL: Case series on the safe use of buprenorphine/naloxone in individuals with acute hepatitis c infection and abnormal hepatic liver transaminases. Am J Drug Alcohol Abuse 2007;33:869-874.
[PubMed]
123.
Houdret N, Asnar V, Szostak-Talbodec N, Leteurtre E, Humbert L, Lecomte-Houcke M, Lhermitte M, Paris JC: Hepatonephritis and massive ingestion of buprenorphine (in French). Acta Clin Belg Suppl 1999;1:29-31.
[PubMed]
124.
Petry NM, Bickel WK, Piasecki D, Marsch LA, Badger GJ: Elevated liver enzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine. Am J Addict 2000;9:265-269.
[PubMed]
125.
Peyriere H, Tatem L, Bories C, Pageaux GP, Blayac JP, Larrey D: Hepatitis after intravenous injection of sublingual buprenorphine in acute hepatitis C carriers: report of two cases of disappearance of viral replication after acute hepatitis. Ann Pharmacother 2009;43:973-977.
[PubMed]
126.
Zuin M, Giorgini A, Selmi C, Battezzati PM, Cocchi CA, Crosignani A, Benetti A, Invernizzi P, Podda M: Acute liver and renal failure during treatment with buprenorphine at therapeutic dose. Dig Liver Dis 2009;41:e8-e10.
[PubMed]
127.
Hervè S, Riachi G, Noblet C, Guillement N, Tanasescu S, Goria O, Thuillez C, Tranvouez JL, Ducrotte P, Lerebours E: Acute hepatitis due to buprenorphine administration. Eur J Gastroenterol Hepatol 2004;16:1033-1037.
[PubMed]
128.
Bogenschutz MP, Abbott PJ, Kushner R, Tonigan JS, Woody GE: Effects of buprenorphine and hepatitis C on liver enzymes in adolescents and young adults. J Addict Med 2010;4:211-216.
[PubMed]
129.
Saxon AJ, Ling W, Hillhouse M, Thomas C, Hasson A, Ang A, Doraimani G, Tasissa G, Lokhnygina Y, Leimberger J, Bruce RD, McCarthy J, Wiest K, McLaughlin P, Bilangi R, Cohen A, Woody G, Jacobs P: Buprenorphine/naloxone and methadone effects on laboratory indices of liver health: a randomized trial. Drug Alcohol Depend 2013;128:71-76.
[PubMed]
130.
Lucas GM, Young A, Donnell D, Richardson P, Aramrattana A, Shao Y, Ruan Y, Liu W, Fu L, Ma J, Celentano DD, Metzger D, Jackson JB, Burns D: Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand. Drug Alcohol Depend 2014;142:139-145.
[PubMed]
131.
Amato L, Minozzi S, Davoli M, Vecchi S: Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Cochrane Database Syst Rev 2011;10:CD004147.
[PubMed]
132.
Dutra L, Stathopoulou G, Basden SL, Leyro TM, Powers MB, Otto MW: A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry 2008;165:179-187.
[PubMed]
133.
Nyamathi A, Cohen A, Marfisee M, Shoptaw S, Greengold B, de Castro V, George D, Leake B: Correlates of alcohol use among methadone-maintained adults. Drug Alcohol Depend 2009;101:124-127.
[PubMed]