Optimizing heroin-assisted treatment (HAT): Assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use
Introduction
Opioid dependence is a major public health problem in many countries associated with high rates of morbidity, life-threatening complications, emergency room visits, crime and premature death from drug overdose, violence, suicide, and alcohol-related causes (Darke and Ross, 2002, European Monitoring Centre for Drugs, 2008). Although numerous medications for the treatment of opioid dependence are under development or have been developed (Vocci et al., 2005), methadone maintenance treatment (MMT) has been established as the treatment of choice for the vast majority of heroin-dependent patients (Kreek and Vocci, 2002, Ward et al., 1999). However, some opiate dependent patients fail to benefit from MMT while others do not feel comfortable with the pharmacological profile of methadone. Therefore, heroin-assisted treatment offering the prescription of pharmaceutical heroin (diacetylmorphine) has been established as a second-line treatment in several countries, including Great Britain, Germany, the Netherlands and Switzerland (Lintzeris, 2009). Alcohol use and related disorders are common clinical problems among opioid users (Wurst et al., 2008). Studies of opioid-dependent individuals have consistently shown a high prevalence of alcohol use including risky alcohol intake, before and during MMT (Wurst et al., 2008, Nyamathi et al., 2009, Teplin et al., 2007). Alcohol use among patients receiving maintenance treatment for opioid dependence may cause significant disability and put a large burden on health care resources (Ryder et al., 2009). For example, MMT patients who drink alcohol are at significantly higher risk of cirrhosis, oesophageal varices and other medical conditions (Nyamathi et al., 2009). Higher mortality and morbidity rates have also been reported for alcohol-using MMT patients (Rowan-Szal et al., 2000). Furthermore, alcohol use may be associated with poor treatment outcome (Li et al., 2007). With the increasing acceptance and more widespread use of HAT, the issue of alcohol consumption is of great clinical relevance since some studies indicate that illicit substance use among HAT patients decreases while alcohol use does not (Perneger et al., 1998). Heavy alcohol consumption may accelerate the progression of hepatitis C (HCV)-related liver disease and/or limit efforts at antiviral treatment in these patients (Peters and Terrault, 2002). Moreover, it might negatively affect the adherence to HAT.
Direct ethanol metabolites such as ethyl glucuronide (EtG) in serum, urine and hair and ethyl sulphate (EtS) in serum and urine may represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers (Wurst et al., 2008, Hannuksela et al., 2007). Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake—EtG and EtS in urine from hours up to 7 days, EtG in hair for months after ethanol has left the body (Wurst et al., 2003, Wurst et al., 2006, Wurst et al., 2008, Kerekes et al., 2009, Weinmann et al., 2004, Halter et al., 2008, Høiseth et al., 2009).
This study is the first to employ direct ethanol metabolites in urine and hair and assess the usefulness in addition to self-reports of alcohol intake among patients on HAT.
Section snippets
Participants
Participants were recruited from the centre for HAT at the Psychiatric Hospital of the University of Basel, Switzerland. This specialized centre offers HAT to a maximum of 150 opioid-dependent patients with multiple and often severe comorbidities. In this treatment program, doses of injectable and oral diacetylmorphine (DAM) are tailored to the needs and the substance-use history of the individual patient and are provided as part of a comprehensive treatment program covering a broad range of
Assessment of alcohol use
Structured (a) and semi-structured (b) instruments were used to assess alcohol use:
- (a)
The 10-item Alcohol Use Disorders Identification Test (AUDIT) is a screening questionnaire developed by the World Health Organization to identify harmful or hazardous alcohol consumption (Saunders et al., 1993). Its utility as a screening instrument for hazardous drinking has also been shown in drug-dependent patients, with a sensitivity of 97%, a specificity of 69% and a positive predictive value of 65% (Skipsey
Statistical analysis
Statistical analysis was performed using SPSS 17 (SPSS Inc., Chicago, IL, USA). Descriptive data are presented as median and range for variables with skewed distribution. Correlations were calculated using Spearman's rank correlation coefficient. The Mann-Whitney test was used to test for sex differences and differences between binge drinkers and non-binge drinkers. All statistical tests were considered significant at p < 0.05.
Results
Of the total of 54 study participants, 41 (75.9%) were HCV positive and 3 (5.6%) were HIV positive (Table 2). AUDIT scores were ≥8 for men in 16 and ≥5 for women in 2 cases, respectively. For direct ethanol metabolites the following results (median, min., max., standard deviation) were found: 26 UEtG positives (10, 0.10–39, 11.65 mg/L); 29 UEtS positives (2.8, 0.10–46.0, 11.13 mg/L); HEtG (60.50, 26.30–142, 36.13 pg/mg): in 1 case no material, 21 abstinent/low alcohol intake, 16 social drinkers
Discussion
This is the first study to assess alcohol intake in HAT patients using direct ethanol metabolites in urine and hair compared to self-reports. The main findings of the study are: (a) HEtG identified 20 cases of daily ethanol intake of more than 20 g that would have been missed by the sole use of questions 1 (frequency) and 2 (quantity) of the AUDIT; (b) using the total score of the AUDIT, HEtG detected 14 additional cases positive for relevant alcohol consumption; and (c) of the 26 participants
Role of funding source
No author mentioned a funding or financial support.
Contributors
FMW, GAW and KD designed the study and wrote the protocol. KD, BL and JS made substantial contributions to the acquisition of data, MY, CH, NT and WW for the analysis and interpretation of data. FMW, NT, KD managed the literature searches and summaries of previous related work. Authors FMW, NT, KD, BL undertook the statistical analysis. FMW, NT, GS, GAW and KD wrote the first draft of the manuscript or revised it critically for important intellectual content. All authors contributed to and have
Conflict of interest
All other authors declare that they have no conflicts of interest. No author mentioned a conflict of interest or financial support.
References (41)
- et al.
Forensic confirmatory analysis of ethyl sulfate – a new marker for alcohol consumption – by liquid-chromatography/electrospray ionization/tandem mass spectrometry
J. Am. Soc. Mass Spectrom.
(2004) Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment
Addict. Behav.
(1978)- et al.
Alcohol use outcomes and heavy drinking at 4–5 years among a treatment sample of drug misusers
J. Subst. Abuse Treat.
(2003) - et al.
Effects of heroin-assisted treatment on alcohol consumption: findings of the German randomized controlled trial
Alcohol
(2009) - et al.
Blood kinetics of ethyl glucuronide and ethyl sulphate in heavy drinkers during alcohol detoxification
Forensic Sci. Int.
(2009) - et al.
History and current status of opioid maintenance treatments: blending conference session
J. Subst. Abuse Treat.
(2002) - et al.
Correlates of alcohol use among methadone-maintained adults
Drug Alcohol Depend.
(2009) - et al.
Utility of the AUDIT for identification of hazardous or harmful drinking in drug-dependent patients
Drug Alcohol Depend.
(1997) - et al.
Role of maintenance treatment in opioid dependence
Lancet
(1999) - et al.
Confirmatory analysis of ethylglucuronide in urine by liquid-chromatography/electrospray-tandem-mass-spectrometry
J. Am. Soc. Mass Spectrom.
(2004)
Antibody testing and RT-PCR results in hepatitis C virus (HCV) infection: HCV-RNA detection in PBMC of plasma viremia-negative HCV-seropositive persons
Infection
Diagnostic value of self-report of alcohol use in patients enrolled in a methadone maintenance treatment program (MMTP)
J. Addict. Dis.
Suicide among heroin users: rates, risk factors and methods
Addiction
Annual Report 2008—The State of the Drugs Problem in Europe
Clinical Global Impression. ECDEU Assessment Manual for Psychopharmacology, Revised National Institute of Mental Health
Heroin-assisted treatment for opioid dependence: randomised controlled trial
Br. J. Psychiatry
Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake
Int. J. Legal Med.
Biochemical markers of alcoholism
Clin. Chem. Lab. Med.
Mass spectrometric identification of ethyl sulfate as an ethanol metabolite in humans
Clin. Chem.
Ethyl glucuronide determination: head hair versus non-head hair
Alcohol Alcohol.
Cited by (13)
Usefulness of hair analysis and psychological tests for identification of alcohol and drugs of abuse consumption in driving license regranting
2018, Forensic Science InternationalCitation Excerpt :Also Wurst et al. [24], after investigated whether biomarkers of alcohol consumption (EtG or FAEE) in hair would provide additional information to the use of the AUDIT test in pregnant women, concluded that the combined use of the AUDIT questionnaire and direct ethanol metabolites identify more potential alcohol consumers than does the sole use of the AUDIT questionnaire. The combined use of self-reports and direct ethanol metabolites seemed also promising to assess alcohol use among patients receiving maintenance treatment for opioid dependence [25,26]. Recently, Ferraguti et al. [27] agreed that the diagnosis of maternal alcohol consumption during pregnancy only based on indirect methods, such as questionnaires, might significantly underestimate alcohol use.
Ethyl glucuronide and ethyl sulfate
2014, Advances in Clinical ChemistryCitation Excerpt :Subjects undergoing opioid maintenance therapy often abuse alcohol, but often deny it with negative AUDIT scores. Urine and hair EtG measurement identified cases of excess alcohol intake in subjects on a methadone maintenance program [81–83]. Many of these would have been missed using self-report alone.
Can ethyl glucuronide in hair be determined only in 3cm hair strands?
2012, Forensic Science InternationalCitation Excerpt :For somewhat other reasons, possibly an easier interpretation of combined EtGH and fatty acids ethyl esters (FAEE) analysis, the first Consensus of the Society of Hair Testing [10] suggested the use of 3 cm hair length for both alcohol markers. There are several studies which document the use of EtGH in hair lengths longer than 3 cm [5,8,11–15]. Unlike FAEE, many studies as the ones mentioned above have shown that EtG concentrations in hair are not dependent on hair length.
Prolonged use of benzodiazepines is associated with childhood trauma in opioid-maintained patients
2011, Drug and Alcohol DependenceCitation Excerpt :There might be more false negative cases, but false positives are rare (Hardt and Rutter, 2004; Hardt et al., 2006). Furthermore, self-reported drug use has been shown to be a reliable measure to assess substance use (Wurst et al., 2008, 2011), which was also demonstrated by the high convergence with urinalysis. Additionally, unwitting ingestion of BZD used to cut street drugs is possible, because 13 of 14 subjects reporting no BZD use but with positive urinalysis, also tested positive for heroin or cocaine.
Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users
2018, Cochrane Database of Systematic ReviewsPrevalence of Heavy Alcohol Use Among People Receiving Methadone Following Change to Methadose
2018, Substance Use and Misuse
- 1
Both authors contributed equally to this work.