G. Fontana Centre for the Study and Treatment of Alcohol Addiction, Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Via Massarenti n°9, 40138 Bologna,
1 Institute of Internal Medicine, Catholic University of Rome,
2 Service for Addiction Treatment, Piacenza,
3 Service for Addiction Treatment, Budrio,
4 Department of Internal Medicine, Ospedale degli Infermi, Faenza and
5 Services for Addiction Treatment (SAT), Emilia Romagna, Italy
Received 2 January 2001; in revised form 25 July 2001; accepted 30 July 2001
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ABSTRACT |
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INTRODUCTION |
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Alcohol dependence affects nearly 10% of the general population both in the United States (McGinnis and Foege, 1993) and in European countries (Hupkens et al., 1993
). In particular, alcohol abuse and its medical complications, together with cocaine use and HIV infection, are the most serious problems found among methadone patients (Bickel et al., 1987
; Stastny and Potter, 1991
; El-Bassel et al., 1993
). Depending on how alcohol addiction is defined, rates of alcoholism vary from 5 to 49% among participants in MMT programmes (Brown, 1973
; Liebson et al., 1973
; El-Bassel et al., 1993
). Up to now, however, data on alcohol consumption during MMT have been controversial (Ottomanelli, 1999
). Some studies suggest that alcoholism increases in methadone patients after their admission to MMT (D'Aunno and Vaughn, 1992
), while others reported a steady alcohol intake (Ball and Ross, 1991
; Fairbank et al., 1993
; Rittmannsberger et al., 2000
). Moreover, methadone patients were less likely to engage in chronic drinking and had a lower intoxication frequency when compared with subjects attending drug education programmes for imprisoned substance abusers and therapeutic communities (Herd, 1993
). Alcohol consumption prior to admission to MMT is also debated: while some authors found that excessive drinking usually existed before admission (Joseph and Appel, 1985
; El-Bassel et al., 1993
; Rittmannsberger et al., 2000
), others reported an inverse relationship between the use of heroin and alcohol long before admission to MMT (Anglin et al., 1989
). However, from 11 to 26% of drop-outs from MMT seem to be due to alcohol use (Joseph and Appel, 1985
), and pre-admission alcohol use appears to be predictive of post-admission level of alcohol misuse in MMT programmes (Kaufman, 1982
; Hunt et al., 1986
; Fairbank et al., 1993
). These data, as a whole, suggest that methadone patients have high rates of alcohol dependence or heavy drinking that adversely affect their programme compliance and physical and mental status (El-Bassel et al., 1993
; Ottomanelli, 1999
).
In the majority of studies performed among methadone patients, alcohol dependence did not represent a criterion for exclusion at the time of admission, and the follow-up period investigating alcohol intake ranged from 3 to 12 months (Rounsaville et al., 1982; Fairbank et al., 1993
; Chatham et al., 1995
; Rittmannsberger et al., 2000
) so that, at present, the effect of methadone administration on alcohol intake by heroin addicts without alcohol dependence in the short term is not known.
The aim of the present study was to investigate changes in alcohol consumption among a population of heroin addicts without alcohol dependence at the time of admission to a treatment programme (TP) within a period of 4 weeks of methadone administration. This evaluation was performed as part of a study carried out by 24 Italian Centres of Addiction Treatment to evaluate drinking habits among a population of illicit drug abuse/dependence subjects admitted to a TP (Caputo et al., 2000).
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PATIENTS AND METHODS |
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In N-MMT patients, symptomatic pharmacological treatment was used to attenuate withdrawal symptoms and support counselling interventions. Most patients followed the commonly used symptom-oriented approach (Schuckit, 2000a), consisting of 0.1500.300 mg of oral clonidine three times daily (t.i.d.) or four times daily (q.i.d.) for 710 days, followed by tapering to zero over the next few weeks. Further treatment, when needed, included: 1216 mg of oral pridinol t.i.d. or q.i.d. to antagonize muscle pain (n = 201; 90.5%); oral metochlopramide (3040 mg) was occasionally used in case of nausea (n = 73; 32.9%); oral lorazepam (7.510 mg t.i.d.) for tearing, sweating and/or insomnia (n = 98; 44.1%); oral promazine (25 mg/day) for restless sleep (n = 86; 38.7%).
In addition to weekly counselling sessions and pharmacological therapy, self-help groups, such as Narcotics Anonymous and social services, were offered and actually used by our patients [n = 68 (64.7%) in MMT group; n = 147 (66.2%) in N-MMT group].
The amount of alcohol intake (recorded as g/day of absolute alcohol) was evaluated on the basis of the participant's self-evaluation and a family member interview at admission and at the end of the first 4 weeks of TP. Moreover, the assessment of abstinence, performed as above, and the determination of urine- and blood-alcohol concentrations, and alcohol in saliva (by Quantitative Ethanol Determination; Enzymatics Inc., Horshman, UK) were carried out at each out-patient control.
Results are expressed as means ± SD. The 2-test was utilized to compare subjects' demographic characteristics. The statistical significance of the difference in alcohol intake between the MMT and N-MMT groups was assessed by the MannWhitney U-test. Comparison of daily alcohol intake both prior to, and 4 weeks after, the beginning of the TP within the N-MMT and MMT groups was performed by the Wilcoxon matched-pairs signed-ranks test. P < 0.05 was considered to be statistically significant.
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RESULTS |
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During the first 4 weeks of TP, alcohol consumption significantly decreased in MMT patients (from 86.2 ± 128.1 to 37.3 ± 67.8 g/day; P < 0.0001), but not in N-MMT patients (from 52.1 ± 85.3 to 49.7 ± 81.5 g/day; P = 0.1).
Out of the total number of patients, 115 (35.2%) [33 (28.7%) in the MMT group and 82 (71.3%) in the N-MMT group] were abstinent. During the follow-up period, 90 (78.3%) of them began to drink alcohol. This occurred more frequently in the N-MMT [70 subjects (85.3%)] than in the MMT group [20 subjects (60.6%); P = 0.006].
Alcohol intake variations in subjects with different methadone dosages are shown in Table 2. In the MMT group, 93 (88.6%) patients were maintained on 5080 mg/day of methadone (mean ± SD: 59.3 ± 8.9 mg/day) and 12 (11.4%) on 90120 mg/day (mean: 97.4 ± 10.6 mg/day). The reduction in alcohol intake reported above reached statistical significance in patients given 5080 mg/day of methadone (from 86.7 ± 126.3 to 36.6 ± 69.9 g/day; P < 0.0001; patients given 90120 mg/day: from 82.7 ± 147.3 to 41.7 ± 49.3 g/day; P = 0.58) (Table 2
). It should also be noted that while subjects who took 50, 60 and 80 mg/day of methadone significantly reduced their drinking (P = 0.009, P = 0.003 and P = 0.04 respectively), the reduction found in those given 70 mg/day did not reach statistical significance (P = 0.26) (Table 2
).
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DISCUSSION |
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Unfortunately, the management of simultaneous heroin and alcohol misuse represents a challenge. In fact, while naltrexone is effective in reducing the number of drinks/day, maintaining abstinence from alcohol and reducing the relapse rate in alcoholic patients (O'Malley et al., 1992; Volpicelli et al., 1992
), it is no more beneficial than placebo in drinking-related outcomes when administered to patients affected by both alcohol dependence and cocaine and opiate abuse (Swift, 1999
). Buprenorphine is efficient in reducing heroin (Wodak, 1994
; O'Connor and Fiellin, 2000
; Pani et al., 2000
), and cocaine (Johnson et al., 2000
) use, but no data are available concerning its use in alcohol addiction. Likewise, no information is available for levomethadyl acetate.
The novel finding of the present study is that short-term methadone administration led to a reduction in alcohol consumption in heroin-addicted patients without alcohol dependence, while N-MMT patients did not significantly reduce their alcohol intake. Moreover, the modification of drinking habits in subjects who were abstinent at the time of admission to TP strengthens our results; in fact, more subjects began to drink alcohol in the N-MMT than in the MMT group. This is an important finding, since the major objective in addiction treatment is to achieve abstinence and avoid new addiction behaviours.
The mechanism(s) by which methadone treatment may elicit a reduction of alcohol consumption cannot be ascertained by our study. However, it can be hypothesized that such an effect may have been due to its action on the µ-receptor system, which may enhance the reward mechanism through dopamine release (Markou et al., 1998). Thus, methadone may act as a substitute rewarding substance with respect to alcohol, which induces a specific craving through this kind of mechanism (Schuckit, 2000b
).
Interestingly, the reduction in alcohol intake in the MMT group was found over a large range of methadone dosages, although no statistical significance was reached in patients consuming 70 and >90 mg/day. It should be noted, however, that the number of subjects in these groups was small, and this may have affected the result of the statistical analysis. Of course, we cannot speculate whether a methadone dosage lower than 50 mg/day may also be effective in reducing alcohol intake, but dosages below 50 mg usually fail to attenuate the effects of injected heroin during MMT (Wodak, 1994; Farrell et al., 1994
; Lowinson et al., 1998
; Ward et al., 1999
; Johnson et al., 2000
).
Our results appear to be in contrast with literature reports showing that alcohol use either increased (D'Aunno and Vaughn, 1992) or did not change during MMT (Ball and Ross, 1991
; Fairbank et al., 1993
; Rittmannsberger et al., 2000
). Moreover, several studies suggest that alcohol consumption in patients interrupting methadone treatment increases, probably to obtain relief from the symptoms of narcotic craving without relapsing into the use of heroin (Bickel et al., 1987
; Ottomanelli, 1999
). However, the majority of studies evaluating alcohol consumption during MMT were carried out on alcohol-dependent subjects, who had been excluded from our study. Alcohol dependence may represent a possible confounding factor, as it may exert a negative impact on the reduction of alcohol consumption during MMT. A further explanation could be the different duration of the follow-up period. While we monitored our patients after 4 weeks of treatment, most previous studies analysed the changes in alcohol consumption after 3, 6 or 12 months of MMT (Rounsaville et al., 1982
; Fairbank et al., 1993
; Chatham et al., 1995
; Rittmannsberger et al., 2000
), and may have missed a possible efficacy of methadone in the first stage of MMT.
Our results are also at variance with the literature in relation to the number of drop-outs we recorded in the N-MMT group, which was considerably lower than that reported by others (O'Connor et al., 1997). The main reason for this discrepancy is probably our short follow-up period (4 weeks). This conclusion is supported by the finding that the main reason for dropping out in our patients (34.4% of cases) was abandonment, which closely matches that found by O'Connor et al. (1997). On the other hand, the drop-out rate of subjects following different kinds of TP varies considerably in different studies. Consistent with our observations, some authors found similar rates between symptomatic and substitute treatments (O'Connor et al., 1997
), while others reported that fewer patients were retained in symptomatic, than in substitute, treatments (Schuckit, 2000a
). On the whole, these results suggest that an unpredictable clinical variability in drop-out rates has to be expected in subjects entering TP.
Our study presents some limitations. First, the subjects enrolled in the study were not randomly assigned to the two treatment groups, but their clinical conditions were such that randomization to different kinds of treatment would have proved impossible to accomplish. For example, subjects who refused methadone therapy or had experienced previous failure of MMT would almost inevitably fail if admitted to MMT. Second, baseline mean alcohol intake differed considerably between the MMT and N-MMT groups, and this may have generated a selection bias, despite the lack of statistically significant differences. On the other hand, the main aim of the present study was to evaluate the possible efficacy of methadone in reducing alcohol intake or maintaining abstinence from alcohol in heroin addicts. In this respect, the number of drinkers did not differ between the MMT and N-MMT groups, thus attenuating the impact of a possible selection bias. Third, information concerning the variations in alcohol intake was entrusted to the patient's own account and interview of a family member. These methods may not always be reliable or sufficient to assess changes in alcohol intake. However, the results of previous studies performed in alcoholics (Addolorato et al., 2000) or methadone patients (Rittmannsberger et al., 2000
) have revealed a satisfactory degree of correspondence between participants' self-evaluation associated with family member interview and variations of laboratory parameters of alcohol misuse.
In conclusion, administration of methadone in heroin-addicted patients without alcohol dependence reduces alcohol intake in a period of 4 weeks and helps to maintain abstinence in subjects who are already abstinent at the time of admission to the treatment programme. This finding is of interest, since methadone might prevent the risk of developing a further condition of dependence involving alcohol as the primary substance of misuse. It is well documented that when patients stop heroin use, their alcohol intake increases, probably due to the use of alcohol as a substitute substance (Bickel et al., 1987; Ottomanelli, 1999
; Caputo et al., 2000
). Despite the favourable results currently achieved (Hutchinson et al., 2000
), the methadone approach for opiate addiction treatment is still controversial, mainly because of the notion that treating a drug-dependent subject with a drug potentially developing addiction is not fully acceptable. The awareness of a dual action of methadone in reducing both opiate craving and heroin use, and alcohol intake could make physicians and practitioners more inclined towards the use of this drug, particularly in heroin addicts with a concurrent alcohol consumption.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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