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Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage
Drug and Alcohol Dependence 52 (1998) 167 – 171
Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage Daniela D’Ippoliti *, Marina Davoli, Carlo A. Perucci, Fulvia Pasqualini, Anna Maria Bargagli Department of Epidemiology, Lazio Regional Health Authority, Via Santa Costanza 53, 00198 Rome, Italy Received 4 November 1997; received in revised form 3 March 1998; accepted 14 April 1998
Abstract Retention in treatment among 1503 heroin users attending public treatment centres in 1995 was studied. Three different treatments were considered: methadone maintenance, drug-free program and naltrexone. The retention rate after 1 year was 40% for patients in methadone maintenance, 18% in naltrexone and 15% in drug-free program. For patients in maintenance, methadone dosage and clinic policy were the most important factors for retention. Patients taking ] 60 mg/day and 30–59 mg/day were respectively 70 and 50% more likely to remain in treatment than those receiving a B 30 mg daily dose. Patients in maintenance-oriented clinics were 30% more likely to remain in treatment than those in abstinence-oriented centres. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Drug abuse treatment; Retention; Methadone maintenance; Methadone dose; Clinic policy
1. Introduction The efficacy of methadone maintenance in reducing the frequency of injecting, the level of criminal activity and improving the social, physical and psychological well-being of drug users, is well documented ( Caplehorn et al., 1993a, Strain et al., 1993a,b, Caplehorn et al., 1994, Farrell et al., 1994, Hartel et al., 1995, Poser et al., 1995). There is evidence that mortality among drug injectors is higher outside methadone maintenance treatment than inside (Caplehorn et al., 1994, Poser et al., 1995) and that risk of death from overdose is higher immediately after drop-out (Davoli et al., 1993, Caplehorn et al., 1996), supporting the theory that methadone maintenance confers a protective effect when individuals are retained in treatment. Different factors have been suggested to affect response to methadone maintenance (Farrell et al., 1994). Among these, dosage is considered an important one (Caplehorn and Bell, * Corresponding author. Tel.: + 39 6 51686469; fax: + 39 6 51686463.
1991, Caplehorn et al., 1993a,b, Strain et al., 1993a,b, Caplehorn et al., 1994, Farrell et al., 1994, Hartel et al., 1995, Poser et al., 1995, Torrens et al., 1996). Despite the existing evidence, the practice of methadone prescription differs widely across countries (Gossop and Grant, 1991, Farrell et al., 1995). In Italy the provision of methadone treatment also differs from region to region, ranging from 23.1% of clients in Emilia Romagna to 81% in Lazio in 1995 (Ministero della Sanita`, 1995). Moreover, even in those regions where methadone treatment is offered to a high proportion of clients, such as Lazio, most patients are on a low-dose gradual detoxification regimen. In Italy treatment policies vary widely between centres and the other main interventions offered to drug users, besides methadone, are drug-free programs and naltrexone. Studies (Thamizan and Ritter, 1997) on highly motivated patients suggest high retention rates in naltrexone treatment, although not yet in a conclusive manner, while no evidence is available for drug-free treatment. The aim of this observational study is, firstly, to compare retention of patients in three different types of
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treatment: methadone maintenance, naltrexone and drug-free program; secondly, to investigate the effect of methadone dosage on retention of heroin users in maintenance treatment, also taking into account treatment policy.
2. Methods
2.1. Background The study was conducted in Lazio, a region with about 5 million inhabitants including the city of Rome. Overall, there are 47 public treatment clinics (PTCs) offering methadone both on detoxification and maintenance basis, naltrexone and drug-free treatment. All treatments are offered free of charge within the National Health Service. More than 95% of drug users attending PTCs are heroin users.
2.2. Subjects and data collection All drug users entering methadone maintenance (n= 721), naltrexone (n =216) and the drug-free program (n = 566) in the first 6 months of 1995 in the region were included in the study and followed till the end of the year. Only for those subjects who dropped out, it was checked if they re-entered treatment during 1995 or the following year. Individual data on drug users’ socio-demographic characteristics, pattern of drug use, type of treatment and methadone dose are routinely collected by clinic staff and delivered to the Department of Epidemiology of the region which manages the surveillance system of drug addiction (D’Ippoliti et al., 1996).
2.3. Treatments In Italy different types of treatment are available for drug dependence, but with no standard protocols for decision making. Treatment strategies vary widely across PTCs and decisions are made by the clinic staff on the basis of drug dependence history, previous treatments, health status and behaviour. Methadone maintenance treatment is offered to patients with history of heavy drug abuse and/or in serious health conditions. Dosage is decided while taking into account these factors. There are no standard admission criteria. Naltrexone treatment is offered to highly motivated subjects after 10–14 days of complete opioid detoxification with clonidine and/or methadone. Complete detoxification is verified through urine analysis or challenge test. A standard dosage of 50 mg daily is offered. Only patients who completed detoxification were included in our study. The drug-free program does not include a
residential phase and consists of counselling, groups and behavioural therapy which are offered after a 2-week detoxification program.
2.4. Data analysis The outcome variable was time in treatment expressed in days. Retention in treatment, as of 31 December 1995, was analysed comparing the different types of treatment. Furthermore, for methadone maintenance, time in treatment was evaluated considering different dosages and clinic policy. Clinic policy was defined as maintenance-oriented if centres offered maintenance treatment to more than 50% of their patients and abstinence-oriented otherwise. Comparisons between groups were made using the x 2-square test for categorical data and by a one factor analysis of variance for continuous variables. Retention in treatment was estimated by the survival analysis method (Cox, 1972). Observations were censored if subjects were still in treatment at the end of the study. ‘Terminations’ referred to voluntary drop-out or forced discharge and ‘loss’ referred to drop-out for causes unrelated to the program (deaths, imprisonment, hospitalisation). For the purpose of the survival analysis, the last two groups were considered as one. For patients in methadone maintenance, the predictor variables of interest were maximum dose and clinic policy. The ‘maximum dose’ variable was categorised into three groups (B 30 mg, 30–59 mg, ] 60 mg) on the basis of the univariate distributions and findings from previous studies (Farrell et al., 1994). Potential confounding variables, identified from literature reviews (Farrell et al., 1994), were explored by bivariate analysis and comparing Kaplan-Meier curves. Outcome related variables were included in a Cox regression model and assessed for conformity to the proportional hazard assumption by plotting log(−log) curves of the Kaplan-Meier survival functions. All variables of interest satisfied the assumption.
3. Results
3.1. Retention in different treatments The characteristics of the 1503 heroin users included in the study are shown in Table 1. They were mostly male, single and with low educational level. The only significant differences among the three treatment groups were age and route of drug use. Subjects on methadone maintenance were older than those on drugfree program and naltrexone treatment, and more likely to be injectors (PB 0.05). The drop-out group (n=956) showed no significant differences in baseline socio-demographic characteris-
D. D’Ippoliti et al. / Drug and Alcohol Dependence 52 (1998) 167–171
169
Table 1 Characteristics of a study group of 1503 heroin users by type of treatment. Lazio, Italy 1995 Type of treatment Drug-free program
Methadone maintenance
Naltrexone
(n= 556)a n.
%
(n = 721)a n.
%
(n =216)a n.
%
Sex Male Female
503 63
88.9 11.1
581 140
80.6 19.4
195 20
90.7 9.3
Marital status Married Unmarried
111 438
20.2 79.8
183 505
26.6 73.4
40 167
19.3 80.7
Educational level Primary/Junior high school High school/university
424 94
81.9 18.1
504 129
79.6 20.4
152 42
78.4 21.6
Employment status Unemployed Ocassionally employed Employed
276 109 140
52.6 20.8 26.6
345 132 147
55.3 21.2 23.5
64 59 66
33.9 31.2 34.9
Route of drug use* Non injecting Injecting
96 434
18.1 81.9
64 611
9.5 90.5
56 144
28.0 72.0
Frequency of use Weekly Once a day More than once a day Age (S.D.)** Age at first use (S.D.)
63 44 292 27.9 20.0
12.6 28.9 58.5 (5.7) (4.1)
130 111 393 31.6 19.9
20.5 17.5 62.0 (6.2) (4.6)
27 45 124 26.6 20.5
13.8 23.0 63.2 (4.8) (4.3)
a
Total may vary because of missing data. * x 2 test, PB0.05. ** AVOVA analysis, PB0.05. No other variables were significantly different among treatment groups.
tics from patients remaining in treatment. Among subjects dropping-out, 396 were on methadone maintenance, 156 on naltrexone and 404 on drug-free treatment. A high proportion (85%), homogeneous across the three treatment groups, returned for new treatment during 1995 or the following year. Retention rates across the three treatment groups were significantly different (P B 0.05) throughout the study period. At the end of the year, the proportion of patients still in treatment was 40% for methadone maintenance, 18% for naltrexone treatment and 15% for drug-free program (Fig. 1). The median time in treatment was 217 days for patients on methadone maintenance compared to 80 days for those on naltrexone treatment and 57 days for clients on drug-free program. While allowing for age and route of drug use, the relative risk of leaving treatment within a year was 0.46 (95% confidence intervals: 0.40 – 0.53) for patients on methadone maintenance and 0.84 (95% confidence intervals: 0.69–1.00) for patients on naltrexone, using the
risk for those patients on drug-free program as the baseline.
3.2. Retention in methadone maintenance Methadone treatment was offered to 47.9% of patients. Out of 47 PTCs, 24 had a maintenance-oriented policy. The average maximum daily dose dispensed in methadone maintenance was 44 mg. Only 23.7% of patients received a dosage ] 60 mg. Retention in methadone maintenance by dosage is shown in Fig. 2. The highest retention rates were always found among patients receiving the highest dosages. Retention in treatment over a year was 54% for patients who received an average maximum daily dose of 60 mg or more, 40% for those between 30 and 59 mg/day and 23% for those with less than 30 mg/day. Retention in treatment is also related to clinic policy: the likelihood of leaving treatment within a year was 30% less (RR= 0.70; 95% CI: 0.56–0.87) for patients who entered maintenance-oriented clinic as compared to patients in abstinence-oriented clinic, independently
170
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Fig. 1. Retention in treatment by type of treatment observed in a study group of 1503 heroin users. Lazio, Italy 1995. Treatment: black line, methadone treatment; grey line, naltrexone; white line, drug free program.
of methadone dosage and age. No statistically significant differences in time in treatment for other variables were found, except for age; older age being associated with higher retention in treatment. The adjusted relative risks are presented in Table 2.
4. Discussion The results of our study confirm methadone maintenance as the most effective in retaining drug users in treatment. We didn’t find high retention rates with
naltrexone treatment. In fact, the retention rate after 1 year was 40% for patients in methadone maintenance, 18% for naltrexone and 15% for the drug-free program. Despite this evidence, in our region only 47.9% of patients entering treatment are offered methadone maintenance. The overall figure of 40% of patients still in treatment after 1 year of methadone maintenance is low when compared with other studies (Caplehorn and Bell, 1991, Caplehorn et al., 1993b, Strain et al., 1993a,b, Hartel et al., 1995, Torrens et al., 1996). This finding may well be explained by the higher average maximum dosage of
Fig. 2. Retention in treatment by methadone dosage observed in a study group 721 heroin users on methadone maintenance. Lazio, Italy, 1995. Maximum dosage: black line, ] 60 mg; grey line, 30–59 mg; white line, B 30 mg.
D. D’Ippoliti et al. / Drug and Alcohol Dependence 52 (1998) 167–171 Table 2 Factors associated with retention in treatment for 721 heroin users on methadone maintenance. Lazio, Italy 1995
a
RR
95% CI
Maximum dosage B30 mg 30–59 mg ]60 mg
1 0.48 0.34
0.37–0.63 0.25–0.47
Centers policy Abstinence-oriented Maintenance-oriented
1 0.70
0.56–0.87
Age B25 years 25–35 years \35 years
1 0.82 0.75
0.61–1.11 0.53–1.05
a
Results from Cox regression model. RR, adjusted relative risk of leaving treatment; 95% CI, 95% confidence intervals.
60 – 80 mg/day reported by these studies compared with the 44 mg used in our region. In fact only 23.7% received a dose that is more likely to reduce injecting and illicit opiate use and to result in retention in treatment. Moreover, our results confirm that methadone dosage and clinic policy are important factors associated with improved retention in treatment. The risk of leaving treatment for patients who received a maximum daily dose of 60 mg or more was almost 70% lower than for those taking less than 30 mg a day. We also found that, while allowing for the effect of methadone dosage, maintenance-oriented clinic policies were associated with increased retention in treatment. However, only 50% of PTCs in our region were found to be maintenance-oriented. Some limitations of this study should be taken into account. Firstly, as in any observational study, results might have been affected by selection bias. In our study, however, none of the other patients’ study variables proved to be independently associated with retention in treatment. Secondly, we cannot exclude the possibility that patients who leave treatment did stop using heroin; however, a high proportion of drop-outs, uniform across treatment groups, returned for a new treatment. In conclusion, despite the evidence of benefit, there is overall gross under provision of methadone maintenance treatment and, even when provided by maintenance-oriented clinics, it seems to be biased towards low dosage. The result is an overall retention in treatment over a 1 year-period of less than half of the cases. Thus, our results suggest that in our region appropriateness and effectiveness of treatments offered by PTCs would be significantly improved by a change in treatment strategies.
171
Acknowledgements The authors are very grateful to Michael Farrell, Bruce R. Aylward, Patrick A. O’Hare and Annette D. Verster for their helpful comments on earlier drafts of this paper.
References Caplehorn, J.R.M., Bell, J., 1991. Methadone dosage and retention of patients in maintenance treatment. Med. J. Aust. 154, 195–199. Caplehorn, J.R.M, Bell, J., Kleinbaum, D.G., Gebski, V.J., 1993a. Methadone dose and heroin use during maintenance treatment. Addiction 88, 119 – 124. Caplehorn, J.R.M., McNeil, D.R., Kleinbaum, D.G., 1993b. Clinic policy and retention in methadone maintenance. Int. J. Addict. 28 (1), 73 – 89. Caplehorn, J.R.M., Dalton, M.S.Y.N., Cluff, M., Petrenas, A.M., 1994. Retention in methadone maintenance and heroin addicts’ risk of death. Addiction 89, 203 – 209. Caplehorn, J.R.M., Dalton, M.S.Y.N., Haldar, F., Petrenas, A.M., Nisbet, J.G., 1996. Methadone maintenance and addicts’ risk of fatal heroin overdose. Subst. Use Misuse 31 (2), 177 – 196. Cox, D.R., 1972. Regression models and life tables. J. R. Stat. Soc. B 34, 187 – 202. Davoli, M., Perucci, C.A., Forastiere, F., et al., 1993. Risk factors for overdose mortality: a case-control study within a cohort of intravenous drug users. Int. J. Epidemiol. 22 (2), 273 – 277. D’Ippoliti, D., Davoli, D., Bargagli, A.M., Pasqualini, F., Perucci, C.A., 1996. Characteristics and outcome of interventions offered to drug users attending public treatment centres in Lazio. Epidemiol. Prev. 20, 37 – 43. Farrell, M., Ward, J., Mattick, R., et al., 1994. Methadone maintenance treatment in opiate dependence: a review. Br. Med. J. 309, 997 – 1001. Farrell, M., Neeleman, J., Gossop, M., Buning, E., Finch, E., Strang, J., 1995. The National Addiction Centre, London, UK (1995) Methadone provision in the European Union. Int. J. Drug Policy 6 (3), 168 – 172. Gossop, M., Grant, M., 1991. A six country survey of the content and structure of heroin treatment programmes using methadone. Br. J. Addict. 86, 1151 – 1160. Hartel, D.M., Schoenbaum, E.E., Selwyn, P.A., et al., 1995. Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use. AJPH 85 (1), 83 – 88. Ministero della Sanita`-Sistema Informativo Sanitario-Dipartimento della Prevenzione e dei Farmaci (1995). Rilevazione attivita` nel settore tossicodipendenze. Poser, W., Koc, J., Ehrenreich, H., 1995. Methadone treatment can reduce mortality. Br. Med. J. 310, 463. Strain, E.C., Stitzer, M.L., Liebson, I.A., Bigelow, G.E., 1993a. Dose-response effects of methadone in the treatment of opioid dependence. Ann. Intern. Med. 119, 23 – 27. Strain, E.C., Stitzer, M.L., Liebson, I.A., Bigelow, G.E., 1993b. Methadone dose and treatment outcome. Drug Alcohol Depend. 33, 105 – 117. Thamizan, T., Ritter, A., 1997. Naltrexone: A literature review. In: Ritter, A., Kutin, J., Lintzeris, N., Bammer, G. (Eds.), Expanding Treatment Options For Heroin Dependence In Victoria: Buprenorphine, LAAM, Naltrexone and Slow-Release Oral Morphine. New Pharmacotherapies Project-Feasibility Phase. Turning Point Alcohol and Drug Centre, Fitzroy, Victoria. Torrens, M., Castillo, C., Perez-Sola, V., 1996. Retention in a lowthreshold methadone maintenance program. Drug Alcohol Depend. 41, 55 – 59.
Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage Daniela D’Ippoliti *, Marina Davoli, Carlo A. Perucci, Fulvia Pasqualini, Anna Maria Bargagli Department of Epidemiology, Lazio Regional Health Authority, Via Santa Costanza 53, 00198 Rome, Italy Received 4 November 1997; received in revised form 3 March 1998; accepted 14 April 1998
Abstract Retention in treatment among 1503 heroin users attending public treatment centres in 1995 was studied. Three different treatments were considered: methadone maintenance, drug-free program and naltrexone. The retention rate after 1 year was 40% for patients in methadone maintenance, 18% in naltrexone and 15% in drug-free program. For patients in maintenance, methadone dosage and clinic policy were the most important factors for retention. Patients taking ] 60 mg/day and 30–59 mg/day were respectively 70 and 50% more likely to remain in treatment than those receiving a B 30 mg daily dose. Patients in maintenance-oriented clinics were 30% more likely to remain in treatment than those in abstinence-oriented centres. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Drug abuse treatment; Retention; Methadone maintenance; Methadone dose; Clinic policy
1. Introduction The efficacy of methadone maintenance in reducing the frequency of injecting, the level of criminal activity and improving the social, physical and psychological well-being of drug users, is well documented ( Caplehorn et al., 1993a, Strain et al., 1993a,b, Caplehorn et al., 1994, Farrell et al., 1994, Hartel et al., 1995, Poser et al., 1995). There is evidence that mortality among drug injectors is higher outside methadone maintenance treatment than inside (Caplehorn et al., 1994, Poser et al., 1995) and that risk of death from overdose is higher immediately after drop-out (Davoli et al., 1993, Caplehorn et al., 1996), supporting the theory that methadone maintenance confers a protective effect when individuals are retained in treatment. Different factors have been suggested to affect response to methadone maintenance (Farrell et al., 1994). Among these, dosage is considered an important one (Caplehorn and Bell, * Corresponding author. Tel.: + 39 6 51686469; fax: + 39 6 51686463.
1991, Caplehorn et al., 1993a,b, Strain et al., 1993a,b, Caplehorn et al., 1994, Farrell et al., 1994, Hartel et al., 1995, Poser et al., 1995, Torrens et al., 1996). Despite the existing evidence, the practice of methadone prescription differs widely across countries (Gossop and Grant, 1991, Farrell et al., 1995). In Italy the provision of methadone treatment also differs from region to region, ranging from 23.1% of clients in Emilia Romagna to 81% in Lazio in 1995 (Ministero della Sanita`, 1995). Moreover, even in those regions where methadone treatment is offered to a high proportion of clients, such as Lazio, most patients are on a low-dose gradual detoxification regimen. In Italy treatment policies vary widely between centres and the other main interventions offered to drug users, besides methadone, are drug-free programs and naltrexone. Studies (Thamizan and Ritter, 1997) on highly motivated patients suggest high retention rates in naltrexone treatment, although not yet in a conclusive manner, while no evidence is available for drug-free treatment. The aim of this observational study is, firstly, to compare retention of patients in three different types of
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treatment: methadone maintenance, naltrexone and drug-free program; secondly, to investigate the effect of methadone dosage on retention of heroin users in maintenance treatment, also taking into account treatment policy.
2. Methods
2.1. Background The study was conducted in Lazio, a region with about 5 million inhabitants including the city of Rome. Overall, there are 47 public treatment clinics (PTCs) offering methadone both on detoxification and maintenance basis, naltrexone and drug-free treatment. All treatments are offered free of charge within the National Health Service. More than 95% of drug users attending PTCs are heroin users.
2.2. Subjects and data collection All drug users entering methadone maintenance (n= 721), naltrexone (n =216) and the drug-free program (n = 566) in the first 6 months of 1995 in the region were included in the study and followed till the end of the year. Only for those subjects who dropped out, it was checked if they re-entered treatment during 1995 or the following year. Individual data on drug users’ socio-demographic characteristics, pattern of drug use, type of treatment and methadone dose are routinely collected by clinic staff and delivered to the Department of Epidemiology of the region which manages the surveillance system of drug addiction (D’Ippoliti et al., 1996).
2.3. Treatments In Italy different types of treatment are available for drug dependence, but with no standard protocols for decision making. Treatment strategies vary widely across PTCs and decisions are made by the clinic staff on the basis of drug dependence history, previous treatments, health status and behaviour. Methadone maintenance treatment is offered to patients with history of heavy drug abuse and/or in serious health conditions. Dosage is decided while taking into account these factors. There are no standard admission criteria. Naltrexone treatment is offered to highly motivated subjects after 10–14 days of complete opioid detoxification with clonidine and/or methadone. Complete detoxification is verified through urine analysis or challenge test. A standard dosage of 50 mg daily is offered. Only patients who completed detoxification were included in our study. The drug-free program does not include a
residential phase and consists of counselling, groups and behavioural therapy which are offered after a 2-week detoxification program.
2.4. Data analysis The outcome variable was time in treatment expressed in days. Retention in treatment, as of 31 December 1995, was analysed comparing the different types of treatment. Furthermore, for methadone maintenance, time in treatment was evaluated considering different dosages and clinic policy. Clinic policy was defined as maintenance-oriented if centres offered maintenance treatment to more than 50% of their patients and abstinence-oriented otherwise. Comparisons between groups were made using the x 2-square test for categorical data and by a one factor analysis of variance for continuous variables. Retention in treatment was estimated by the survival analysis method (Cox, 1972). Observations were censored if subjects were still in treatment at the end of the study. ‘Terminations’ referred to voluntary drop-out or forced discharge and ‘loss’ referred to drop-out for causes unrelated to the program (deaths, imprisonment, hospitalisation). For the purpose of the survival analysis, the last two groups were considered as one. For patients in methadone maintenance, the predictor variables of interest were maximum dose and clinic policy. The ‘maximum dose’ variable was categorised into three groups (B 30 mg, 30–59 mg, ] 60 mg) on the basis of the univariate distributions and findings from previous studies (Farrell et al., 1994). Potential confounding variables, identified from literature reviews (Farrell et al., 1994), were explored by bivariate analysis and comparing Kaplan-Meier curves. Outcome related variables were included in a Cox regression model and assessed for conformity to the proportional hazard assumption by plotting log(−log) curves of the Kaplan-Meier survival functions. All variables of interest satisfied the assumption.
3. Results
3.1. Retention in different treatments The characteristics of the 1503 heroin users included in the study are shown in Table 1. They were mostly male, single and with low educational level. The only significant differences among the three treatment groups were age and route of drug use. Subjects on methadone maintenance were older than those on drugfree program and naltrexone treatment, and more likely to be injectors (PB 0.05). The drop-out group (n=956) showed no significant differences in baseline socio-demographic characteris-
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169
Table 1 Characteristics of a study group of 1503 heroin users by type of treatment. Lazio, Italy 1995 Type of treatment Drug-free program
Methadone maintenance
Naltrexone
(n= 556)a n.
%
(n = 721)a n.
%
(n =216)a n.
%
Sex Male Female
503 63
88.9 11.1
581 140
80.6 19.4
195 20
90.7 9.3
Marital status Married Unmarried
111 438
20.2 79.8
183 505
26.6 73.4
40 167
19.3 80.7
Educational level Primary/Junior high school High school/university
424 94
81.9 18.1
504 129
79.6 20.4
152 42
78.4 21.6
Employment status Unemployed Ocassionally employed Employed
276 109 140
52.6 20.8 26.6
345 132 147
55.3 21.2 23.5
64 59 66
33.9 31.2 34.9
Route of drug use* Non injecting Injecting
96 434
18.1 81.9
64 611
9.5 90.5
56 144
28.0 72.0
Frequency of use Weekly Once a day More than once a day Age (S.D.)** Age at first use (S.D.)
63 44 292 27.9 20.0
12.6 28.9 58.5 (5.7) (4.1)
130 111 393 31.6 19.9
20.5 17.5 62.0 (6.2) (4.6)
27 45 124 26.6 20.5
13.8 23.0 63.2 (4.8) (4.3)
a
Total may vary because of missing data. * x 2 test, PB0.05. ** AVOVA analysis, PB0.05. No other variables were significantly different among treatment groups.
tics from patients remaining in treatment. Among subjects dropping-out, 396 were on methadone maintenance, 156 on naltrexone and 404 on drug-free treatment. A high proportion (85%), homogeneous across the three treatment groups, returned for new treatment during 1995 or the following year. Retention rates across the three treatment groups were significantly different (P B 0.05) throughout the study period. At the end of the year, the proportion of patients still in treatment was 40% for methadone maintenance, 18% for naltrexone treatment and 15% for drug-free program (Fig. 1). The median time in treatment was 217 days for patients on methadone maintenance compared to 80 days for those on naltrexone treatment and 57 days for clients on drug-free program. While allowing for age and route of drug use, the relative risk of leaving treatment within a year was 0.46 (95% confidence intervals: 0.40 – 0.53) for patients on methadone maintenance and 0.84 (95% confidence intervals: 0.69–1.00) for patients on naltrexone, using the
risk for those patients on drug-free program as the baseline.
3.2. Retention in methadone maintenance Methadone treatment was offered to 47.9% of patients. Out of 47 PTCs, 24 had a maintenance-oriented policy. The average maximum daily dose dispensed in methadone maintenance was 44 mg. Only 23.7% of patients received a dosage ] 60 mg. Retention in methadone maintenance by dosage is shown in Fig. 2. The highest retention rates were always found among patients receiving the highest dosages. Retention in treatment over a year was 54% for patients who received an average maximum daily dose of 60 mg or more, 40% for those between 30 and 59 mg/day and 23% for those with less than 30 mg/day. Retention in treatment is also related to clinic policy: the likelihood of leaving treatment within a year was 30% less (RR= 0.70; 95% CI: 0.56–0.87) for patients who entered maintenance-oriented clinic as compared to patients in abstinence-oriented clinic, independently
170
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Fig. 1. Retention in treatment by type of treatment observed in a study group of 1503 heroin users. Lazio, Italy 1995. Treatment: black line, methadone treatment; grey line, naltrexone; white line, drug free program.
of methadone dosage and age. No statistically significant differences in time in treatment for other variables were found, except for age; older age being associated with higher retention in treatment. The adjusted relative risks are presented in Table 2.
4. Discussion The results of our study confirm methadone maintenance as the most effective in retaining drug users in treatment. We didn’t find high retention rates with
naltrexone treatment. In fact, the retention rate after 1 year was 40% for patients in methadone maintenance, 18% for naltrexone and 15% for the drug-free program. Despite this evidence, in our region only 47.9% of patients entering treatment are offered methadone maintenance. The overall figure of 40% of patients still in treatment after 1 year of methadone maintenance is low when compared with other studies (Caplehorn and Bell, 1991, Caplehorn et al., 1993b, Strain et al., 1993a,b, Hartel et al., 1995, Torrens et al., 1996). This finding may well be explained by the higher average maximum dosage of
Fig. 2. Retention in treatment by methadone dosage observed in a study group 721 heroin users on methadone maintenance. Lazio, Italy, 1995. Maximum dosage: black line, ] 60 mg; grey line, 30–59 mg; white line, B 30 mg.
D. D’Ippoliti et al. / Drug and Alcohol Dependence 52 (1998) 167–171 Table 2 Factors associated with retention in treatment for 721 heroin users on methadone maintenance. Lazio, Italy 1995
a
RR
95% CI
Maximum dosage B30 mg 30–59 mg ]60 mg
1 0.48 0.34
0.37–0.63 0.25–0.47
Centers policy Abstinence-oriented Maintenance-oriented
1 0.70
0.56–0.87
Age B25 years 25–35 years \35 years
1 0.82 0.75
0.61–1.11 0.53–1.05
a
Results from Cox regression model. RR, adjusted relative risk of leaving treatment; 95% CI, 95% confidence intervals.
60 – 80 mg/day reported by these studies compared with the 44 mg used in our region. In fact only 23.7% received a dose that is more likely to reduce injecting and illicit opiate use and to result in retention in treatment. Moreover, our results confirm that methadone dosage and clinic policy are important factors associated with improved retention in treatment. The risk of leaving treatment for patients who received a maximum daily dose of 60 mg or more was almost 70% lower than for those taking less than 30 mg a day. We also found that, while allowing for the effect of methadone dosage, maintenance-oriented clinic policies were associated with increased retention in treatment. However, only 50% of PTCs in our region were found to be maintenance-oriented. Some limitations of this study should be taken into account. Firstly, as in any observational study, results might have been affected by selection bias. In our study, however, none of the other patients’ study variables proved to be independently associated with retention in treatment. Secondly, we cannot exclude the possibility that patients who leave treatment did stop using heroin; however, a high proportion of drop-outs, uniform across treatment groups, returned for a new treatment. In conclusion, despite the evidence of benefit, there is overall gross under provision of methadone maintenance treatment and, even when provided by maintenance-oriented clinics, it seems to be biased towards low dosage. The result is an overall retention in treatment over a 1 year-period of less than half of the cases. Thus, our results suggest that in our region appropriateness and effectiveness of treatments offered by PTCs would be significantly improved by a change in treatment strategies.
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Acknowledgements The authors are very grateful to Michael Farrell, Bruce R. Aylward, Patrick A. O’Hare and Annette D. Verster for their helpful comments on earlier drafts of this paper.
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