Opioid agonist pharmacotherapy in New South Wales from 1985 to 2006: patient characteristics and patterns and predictors of treatment retention

Opioid agonist pharmacotherapy in New South Walesfrom 1985 to 2006: patient characteristics andpatterns and predictors of treatment retentionadd_2633 1363..1372

Lucy Burns1, Deborah Randall1, Wayne D. Hall2, Matthew Law3, Tony Butler4, James Bell5 &Louisa Degenhardt1

National Drug and Alcohol Research Centre, University of New South Wales, Sydney,1 School of Population Health, University of Queensland, Brisbane,2 NationalCentre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney,3 National Drug Research Institute, Curtin University of Technology,Perth4 and The Langton Centre, Sydney, Australia5

ABSTRACT

Aims The aims of this study were to: examine the number and characteristics of patients entering and re-enteringopioid replacement treatment between 1985 and 2006, to examine select demographic and treatment correlates ofleaving treatment between 1985 and 2000, and to compare retention rates in methadone and buprenorphine main-tenance treatment from 2001 to 2006. Design A retrospective cohort study using register data from the Pharma-ceutical Drugs of Addiction System. Setting Opioid substitution treatment in New South Wales (NSW), Australia.Participants A total of n = 42 690 individuals prescribed opioid replacement treatment between 1985 and 2006 inNSW. Measurements Client characteristics over time, retention in days in first treatment episode, number of episodesof treatment and proportion switching medication. Findings Overall, younger individuals were significantly morelikely to leave their first treatment episode than older individuals. In 2001–06, after controlling for age, sex and firstadministration point, the hazard of leaving treatment was 1.9 times for those on buprenorphine relative to those onmethadone. Retention in treatment varied somewhat across historical time, with those entering during 1995–2000more likely to leave at an earlier stage than those who entered before that time. Conclusions Retention in treatmentappears to fluctuate in inverse proportion to the availability of heroin. Individuals in contemporary treatment are olderusers with a lengthy treatment history. This study has provided population-level evidence to suggest that retention inmethadone and buprenorphine differ in routine clinical practice. Future work might investigate ways in which patientadherence and retention may be improved.

Keywords Buprenorphine maintenance, cohort studies, data linkage, heroin dependence rehabilitation, metha-done maintenance.

Correspondence to: Lucy Burns, National Drug and Alcohol Research Centre, University of NSW, Sydney, NSW 2052, Australia.E-mail: [email protected] 21 October 2008; initial review completed 12 January 2009; final version accepted 27 March 2009

INTRODUCTION

Illicit heroin markets developed in Australia in the late1960s, largely as a result of heroin-dependent Americansoldiers on ‘rest and recreation’ leave from Vietnam [1,2].The subsequent uptake of heroin by locals ensured thatdemand for heroin continued in the post Vietnam-warera after these servicemen departed Australian shores[2]. As the number of dependent users grew throughoutthe 1970s [3], so did the realization that treatment wasneeded for those requesting help for heroin addiction.

Methadone maintenance programmes were establishedin Australia in the 1970s to respond to this need, and theprogramme expanded after 1985 with Federal govern-ment funding for methadone maintenance treatmentunder the National Campaign Against Drug Abuse.

Methadone is a long-acting orally administered opioidagonist with a half-life of about 24–36 hours. Multiplerandomized controlled trials have found that methadonetreatment decreases illicit opioid use, improves socialfunctioning, decreases offending behaviours andimproves health [4,5]. Longer retention in opioid

RESEARCH REPORT doi:10.1111/j.1360-0443.2009.02633.x

© 2009 The Authors. Journal compilation © 2009 Society for the Study of Addiction Addiction, 104, 1363–1372

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replacement therapy (ORT) is associated with greaterimprovements in health and well-being, making it aproxy indicator for positive outcomes in opioid-dependentindividuals [4]. In this light, ORT in contemporary Aus-tralia is geared towards stabilization—where opioidintoxication and withdrawal are minimized, and there isno limitation on the length of time a client may remain intreatment. Rather, clients are encouraged to remain intreatment for at least 12 months to achieve enduringlife-style changes [6]. While the provision of an opioidsubstitute is the mainstay of the programme, clients mayalso receive additional counselling and social services,provided according to individual need.

However, as the number of individuals with opioiddependence increased in Australia throughout the 1980s[3], it became apparent that methadone treatment didnot meet the needs of all opioid-dependent individuals.Many people who left methadone treatment, particularlyafter short episodes, relapsed subsequently to heroin use[7]. The need for supervised daily dosing in a definedtreatment setting, together with recognition that metha-done did not halt illicit opioid use in all individuals,prompted the search for alternative treatment options[8].

Buprenorphine was made available as an ORT in NewSouth Wales (NSW) in 2001. Buprenorphine is a partialopioid receptor agonist that has been shown to be effec-tive in retaining people in treatment and suppressingheroin use [5]. As a partial agonist, buprenorphine is notassociated with the depression of respiration and con-sciousness that occurs with methadone, and therebyreduces the risk of fatal overdose. Buprenorphine has alonger duration of action than methadone, allowing lessthan daily dosing. It has the disadvantages of increasedtime to administer compared with methadone (taking4–10 minutes to be absorbed sublingually), and somepatients may be unable to achieve optimal absorptionthrough the oral route. Further, buprenorphine can alsobe diverted more easily to unintended uses, as it can besecreted in the mouth and removed later [6]. This poten-tial for diversion makes its use less attractive in correc-tional settings.

To date, most studies of treatment for opioid depen-dence have been undertaken as clinical trials testing theefficacy of alternative therapies, or they have examinedthe treatment patterns of methadone alone [9–11]. Arecent prospective German study of a nationally repre-sentative study of heroin-dependent patients in treat-ment found that 70% were retained in treatment atfollow-up, but did not examine factors associated withretention past the 12-month follow-up period [12].Studies conducted on small cohorts of individuals intreatment in NSW have shown that there is relatively lowretention in treatment in NSW compared to international

benchmarks, and that patients cycle in and out of treat-ment [13].

The current study represents the largest and mostcomprehensive examination of an ORT programme inAustralia, with data on every treatment episode forpatients receiving treatment in NSW between 1985 and2006 inclusive. The specific aims of this study were to:

1 examine the characteristics of the treatment cohortbetween 1985 and 2006;

2 examine retention in treatment and determine factorsassociated with leaving treatment prior to successfulcompletion between 1985 and 2000; and

3 track methadone and buprenorphine maintenancetreatment under conditions of routine clinical practicebetween 2001 and 2006.

METHODS

NSW is the most populous state in Australia, withapproximately 6 million residents, and it has the largestopioid replacement programme in Australia. The NSWmethadone programme requires central approval for anydispensation of methadone or buprenorphine used totreat opioid dependence, and the NSW PharmaceuticalDrugs of Addiction System (PHDAS) compiles a databasethat records each authority to dispense methadone orbuprenorphine in NSW once approved by the NSWHealth Department. This study examined de-identifiedunit record data from all people entering the PHDAS data-base between 1985 and 2006.

In PHDAS a new treatment programme is countedeach time an application to prescribe methadone orbuprenorphine to a particular client is approved by theNSW Director-General of Health, or if a client changestheir prescriber. A person may therefore have multipletreatment programmes. In this study, we defined anepisode of continuous treatment in ORT as one withno more than a 6-day break between treatment pro-grammes. Where a gap of 7 days or greater occurredbetween an exit date and a start date for a new pro-gramme, a new episode of treatment was defined. Weadopted this definition following consultation withexperts in clinical research and practice [13]. Recordswere excluded from the analysis if the person was on atemporary programme (usually interstate transfers), wasrecorded as ‘did not commence treatment’, was registeredon the buprenorphine clinical trial, had the same pro-gramme start and end date, or if the programme end datepreceded the start date.

Ethics clearance was obtained from the NSW Popula-tion and Health Services Research Ethics Committee. Allresearch involving access to State-wide data collectionsowned or managed by the NSW Health Department isreviewed by this committee.

1364 Lucy Burns et al.


Variables examined in this study were: age, sex, type oftreatment (methadone or buprenorphine), first treatmentsetting (clinic, correctional facility, community phar-macy or other), date of commencement of a treatmentepisode, date and reason for leaving a treatment episodeand dates of subsequent entries and exits. Clinicsincluded private or public specialized centres staffedusually by multi-disciplinary teams; correctional facilitiescovered prisons and juvenile detention centres;community pharmacies included community and retailpharmacies authorized to provide methadone andbuprenorphine dosing; and others included public hospi-tals, general practitioners and any unknown dosingcentres [6]. To examine changing retention over time wecompared new entrants’profiles during five time-periods—1986, 1991, 1996, 2001 and 2006 using theCochrane–Armitage test for trends. Clients newly enter-ing treatment and those already retained in treatmentwithin these time-periods were compared using the c2

test. Both analyses were implemented in SAS (version9.1.3; SAS Institute Inc., Cary, NC, USA). Predictors ofretention in treatment were analysed using Cox pro-portional hazards regression using STATA statisticalsoftware (version 9.2; StataCorp LP, College Station,TX, USA). The final regression model was built usingbackwards elimination.

RESULTS

Characteristics of the treatment cohort, 1985–2006

Between 1985 and 2006, a total of 42 690 individualswere treated with ORT in NSW (Fig. 1). The number of‘new entrants’ to the programme (i.e. those who enteredORT in NSW for the first time) was 1837 in 1985, peakedin 2000 at 2832 and decreased to 1286 in 2006. Thetotal number of people with at least one treatmentepisode over a 1-year period increased steadily to a peak of19 693 in 2004 and dropped slightly to 19 359 in 2006

as result of fewer new entrants. The median episodelength in the cohort was 197 days and the averagenumber of episodes was 2.5.

Table 1 compares the characteristics of new andretained/returned clients in 1986, 1991, 1996, 2001and 2006. The proportion of new entrants aged 40 yearsor over increased over the time-period (Cochrane–Armitage test for trend Z = 15.7, P < 0.001) and themedian age of those retained in treatment increased overtime, suggesting that the cohort of opioid-dependentindividuals, in and out of treatment, is ageing. Propor-tionally fewer women than men commenced treatment in1986 (39%), and the percentage of new entrants whowere male increased from 61% in 1986 to 71% in 2006(Cochrane–Armitage test for trend Z = 5.3, P < 0.001).Individuals were most likely to be initiated into treatmentat a clinic. This proportion was highest in 1996 (when84% of new clients were first dosed at a clinic) anddecreased to 54% of new clients in 2006. The proportionfirst dosed at a correctional facility increased over time(from 5% in 1985 to 27% in 2006, Cochrane–Armitagetest for trend Z = 19.6, P < 0.001).

Retention in treatment, 1985–2000

Figure 2 shows the percentage of clients retained con-tinuously in treatment at 3, 6 and 12 months from1985 to 2000, before the introduction of buprenor-phine. In 1985, 65% of clients were retained in continu-ous treatment at 3 months, 59% at 6 months and 50%at 12 months. Retention rates peaked in 1989, when76%, 64% and 49% were retained at 3, 6 and 12months, respectively. Retention rates then decreased atall time-points until 1995 and appeared to rise again in2000, with 65% of clients still in their first treatmentepisode at 3 months, 54% at 6 months, and 41% at12 months.

A Cox proportional hazards analysis was used to deter-mine the predictors of leaving first treatment episode

Figure 1 Numbers of patients in theopioid replacement therapy by year

Retention in opioid agonist pharmacotherapy 1365


before successful completion for the period 1985–2000.The following variables were included in the model: sex,age group, first treatment setting and year of entry totreatment (Table 2). The analysis excluded those cases(n = 31) where there was an incorrect start or end date tothe programme (e.g. the end date was before the startdate) that could not be resolved through audit or review.Clients who completed their first treatment episode suc-cessfully (as noted in the database) were considered as‘not failing’ and were therefore censored at the end of

their first episode. Similarly, those clients who transferredinterstate were censored at the end of their episode inNSW.

For those first treated in a correctional facility, thehazards were not proportional over time. In order to takethis into account, the regression model included a func-tion of first administration type and time - admin ¥ ln(t),with time a dichotomous variable split at 9 months,approximately the time at which the risk of leaving treat-ment before completion changed among those in a

Table 1 Comparison of the characteristics of new and retained clients in opioid replacement therapy in 1986, 1991, 1996, 2001 and2006.

YearTestfor trenda1986 1991 1996 2001 2006

Age % % % % %Started treatment <20 years 4.0 5.7 11.6 11.2 5.8

20–29 years 66.6 54.9 55.3 53.5 52.130–39 years 28.2 34.6 25.6 27.0 26.140+ years 1.2 4.9 7.5 8.3 15.9 Z = 15.7,

P < 0.001Median 27.5 28.3 26.4 26.5 28.2

Retained/re-entered <20 years 1.8 1.0 1.3 1.6 0.520–29 years 56.7 40.4 29.4 29.2 23.930–39 years 40.0 52.3 51.4 39.6 36.140+ years 1.6 6.3 17.9 29.6 39.6Median 29.0 31.2 33.8 34.9 37.0c2

(3) = 65 259 1486 1284 994P = <0.001 <0.001 <0.001 <0.001 <0.001

SexStarted treatment Female 39.0 34.6 31.2 35.3 28.7

Male 61.1 65.4 68.8 64.7 71.3 Z = 5.3,P < 0.001

Retained/re-entered Female 42.2 37.6 36.5 35.7 34.6Male 57.8 62.4 63.5 64.3 65.5c2

(1) = 4 4 25 0 18P = 0.053 0.036 <0.001 0.736 <0.001

First administration pointStarted treatment Clinic 59.8 77.8 83.9 68.3 53.7

Correctional facility 4.9 10.4 5.9 18.1 27.0 Z = 19.6,P < 0.001

Community pharmacy 16.2 6.8 7.9 10.9 10.2Other 19.2 5.1 2.4 2.7 9.2

Retained/re-entered Clinic 47.8 74.8 77.8 74.5 70.4Correctional facility 3.1 10.2 8.5 11.1 13.2Community pharmacy 31.0 9.3 10.7 11.9 12.7Other 18.1 5.8 3.0 2.5 3.8c2

(3) = 116 10 45 83 301P = <0.001 0.016 <0.001 <0.001 <0.001

Number started treatment 2018 1402 2467 1935 1286Number retained/re-entered treatment 1544 5937 11 113 16 029 18 073

aCochrane–Armitage test for trend.



correctional facility from being lower to higher thanthose in a clinic.

Of the variables in the model, age group had thebiggest impact on the risk of leaving treatment. Thehazard of leaving treatment decreased with increasingage: a person aged 40 years or older had less than half thehazard of leaving treatment than someone who was lessthan 20 years, if they were in the same categories on allother variables. The year of treatment had a lesser effecton retention: clients who started treatment between1995 and 2000 had an approximately 25% higher risk ofleaving treatment at any time than those in the earlier

(1985–1989) cohort. Males were slightly (although sig-nificantly) more likely to leave their first treatmentepisode than females.

Those whose first treatment episode was in a correc-tional facility were significantly less likely to leave treat-ment in the first 9 months than those who first started ina clinic. For clients who were still in treatment after 9months, however, the relationship changed direction andthose who started in corrections were more likely to leavetreatment than those who first started in a clinic. Acrossboth follow-up periods, those who were first treated in acommunity pharmacy were significantly less likely to

Figure 2 Percentage of clients first dosedwith methadone and subsequently in con-tinuous treatment at 3, 6 and 12 months, byyear of entry

Table 2 Cox proportional hazards model of leaving the first treatment episode, splitting the follow-up at 9 months.

Hazard ratio (95% CI) P-value

Predictor variablesMale 1.16 (1.13–1.19) P < 0.001Female Ref.

40+ 0.45 (0.42–0.49) P < 0.00130–39 0.55 (0.53–0.58) P < 0.00120–29 0.75 (0.72–0.79) P < 0.001<20 years Ref.1995–2000 1.24 (1.19–1.28) P = 0.0281990–94 0.96 (0.92–1.00) P < 0.0011985–89 Ref.First 9 months of treatment

Correctional facility 0.61 (0.56–0.65) P < 0.001Community pharmacy 0.68 (0.64–0.72) P < 0.001Other 0.83 (0.76–0.90) P < 0.001Clinic Ref.

P < 0.001After 9 months in treatment P < 0.001

Correctional facility 1.18 (1.09–1.28) P = 0.095Community pharmacy 0.86 (0.80–0.92) P < 0.001Other 1.09 (0.99–1.20)Clinic Ref.

Ref. = referent category; CI: confidence interval.



leave treatment than those whose first treatment wasa clinic.

Retention in treatment, 2001–06

Buprenorphine was introduced as an alternative ORT in2001. Between 2001 and 2006, 59% of new clientswere first prescribed methadone and 41% were first pre-scribed buprenorphine. Buprenorphine clients weremore likely to be prescribed from a clinic (73%) thanmethadone clients (59%), while methadone clients weremore likely to be prescribed from a correctional facilitythan buprenorphine clients (26% versus 4%; Table 3).There were only small differences in the age and sexprofile of those first prescribed buprenorphine andmethadone.

Between 2001 and 2005 (allowing a full year offollow-up to end 2006), 39% of those who were firsttreated with buprenorphine were still in continuous

treatment at 3 months. This dropped to 29% at 6 monthsand 21% at 12 months. This retention compared to 69%,57% and 44% at 3, 6 and 12 months, respectively, forclients who commenced on methadone (improving since2000; Fig. 2). During this time, buprenorphine was anew treatment and methadone was well established, andwhile 3- and 6-month retention percentages were stablefor buprenorphine, the percentage of clients retained at12 months increased from 19% to 24% (Cochrane–Armitage test for trend Z = 2.9, P = 0.003) (Fig. 3).

Those clients commencing treatment on buprenor-phine were more likely to switch medications at least once(c2

(2) = 341.2, P < 0.001). A change in medication wasnot considered a new treatment episode unless there wasa break of 7 days or more. Those clients who commencedtheir first treatment episode on buprenorphine werealso more likely to have multiple treatment episodes(c2

(2) = 453.3, P < 0.001): 17% of those who first startedon methadone had three or more subsequent treatment

Table 3 Patient profile by medication type (buprenorphine or methadone) in first treatment episode: 2001–06.

First medication type

Buprenorphine(n = 4493)

Methadone(n = 6336)

n Col % n Col %

Sex c2(1) = 10, P = 0.002

Female 1312 29.2 2027 32.0Male 3181 70.8 4309 68.0

Age group c2(3) = 14, P = 0.003

<20 years 401 8.9 581 9.220–29 years 2436 54.2 3209 50.630–39 years 1155 25.7 1762 27.840+ years 501 11.2 784 12.4

First administration point c2(3) = 1324, P < 0.001

Clinic 3263 72.6 3717 58.7Correctional facility 180 4.0 1668 26.3Community pharmacy 389 8.7 756 11.9Other 661 14.7 195 3.1

(a) Methadone (b) Buprenorphine

Figure 3 Percentage of clients firstdosed with methadone and subsequentlyin continuous treatment at 3, 6 and 12months by year of entry and first medica-tion type—2001–05. (a) Methadone; (b)buprenorphine



episodes while 32% who commenced on buprenorphinehad three or more.

Because of switching between medications during thefirst treatment episode, we examined the impact of treat-ment type on retention in the Cox regression model byusing a time-varying covariate for medication (Table 4).This meant that the risk of leaving treatment early bymedication type was based on the medication eachpatient was receiving when they left treatment ratherthan the medication first prescribed. This analysis waslimited to the time-period after buprenorphine was intro-duced (2001–06). As with the previous regression, weincluded a function of time and administration point (thetime before and after 6 months in treatment), and did notinclude the one case with a programme end date beforethe start date. After controlling for age, sex and firstadministration point, those who were prescribedbuprenorphine were almost twice as likely to drop out oftreatment at any point as those prescribed methadone(Table 4).

DISCUSSION

This paper provides a comprehensive population-basedexamination of the dynamics of opioid agonist pharma-cotherapy in those receiving this form of treatment inNSW over a 20-year period. It also compares the nature oftreatment episodes and retention in treatment for

patients receiving buprenorphine and methadone. Theseanalyses have revealed policy-relevant and clinicallyimportant findings.

Key findings

First, we found clear evidence of an ageing cohort ofopioid-dependent individuals over the study period. Thisis consistent with other data showing fewer youngerpeople initiating heroin use since 2001 [14–16]. Sec-ondly, we found that retention in methadone treatmentdid not change dramatically over time but it was lowerwhen other data indicated that heroin was very readilyavailable in NSW during the mid-1990s. Thirdly, the firsttreatment episode was shorter, on average, for thosewho commenced treatment on buprenorphine, com-pared with methadone. Buprenorphine clients were alsomore likely to switch subsequently to methadone thanwere methadone clients to switch to buprenorphine.

Characteristics of the treatment cohort

Our study found evidence of both an ageing cohort ofpatients in ORT and decreasing numbers of new entrantsto the ORT treatment programme. This is in concordancewith research that found the Australian reduction inheroin supply was associated with fewer treatment-naiveindividuals entering treatment [17]. These authorshypothesized that treatment-naive people may have beenless motivated to maintain use of a drug that had becomeless pure, more expensive and harder to obtain, and wereless motivated to enter treatment to replace heroin withan alternative opioid than older users with a longerhistory of heroin use.

There were more males in the treatment cohort thanfemales, and the proportion of males increased over thestudy period, due partly to the increasing treatment pro-vision in correctional facilities.

Retention in treatment 1985–2000

According to the NSW clinical guidelines for treatment,‘patients should be encouraged to remain in treatment forat least 12 months to achieve enduring lifestyle changes’[6]. Duration of first treatment episode has been found topredict retention in later treatment episodes [13], so thiswas the focus of our analysis on treatment retention.Overall, retention in methadone treatment has notchanged demonstrably over time. There have been somefluctuations: clients starting treatment between 1995and 2000 were more likely to leave treatment than thosein the first cohort of 1985–89. These fluctuations intreatment retention may reflect patterns of heroinavailability [17]. Retention declined when heroin useincreased in the mid-1990s in response to historically low

Table 4 Cox proportional hazards model of leaving the firsttreatment episode between 2001 and 2006.

Hazard ratios P-value

Predictor variablesBuprenorphine 1.89 (1.79–1.99) P < 0.001Methadone Ref.Male 1.14 (1.08–1.21) P < 0.001Female Ref.40+ 0.55 (0.49–0.61) P < 0.00130–39 0.75 (0.69–0.82) P < 0.00120–29 0.84 (0.77–0.91) P < 0.001<20 years Ref.First 6 months of treatment

Correctional facility 0.76 (0.69–0.83) P < 0.001Community pharmacy 0.44 (0.38–0.50) P < 0.001Other 0.96 (0.85–1.08) P = 0.512Clinic Ref.

P < 0.001After 6 months of

treatmentP < 0.001

Correctional facility 1.94 (1.76–2.15) P < 0.001Community pharmacy 0.65 (0.56–0.76) P < 0.001Other 0.63 (0.49–0.82)Clinic Ref.

Ref. = referent category.



prices and an estimated 60% purity [18]. Retention inmethadone treatment improved after 2001, following adramatic decline in the availability of heroin, initially inSydney then Australia-wide—the so-called ‘heroin short-age’ when heroin prices rose steeply, and purity declinedto less than 20% [19]. Several Australian drug use indi-cators suggest that the availability of heroin in Australiahas currently not returned to pre-shortage levels [15].

There was a clinically significant age effect, withyounger clients most likely to leave before successfulcompletion. Males were slightly more likely to leave theirfirst treatment episode than were females. We foundretention was poorer when a client was first dosed in aclinic in comparison to a pharmacy. In New South Wales,dosing point is dependent upon a range of factors, bothindividual and agency. These include: the availability ofplaces at the dosing point and hours of opening, as well asclient characteristics such as functionality and financialstatus. Clinics are recommended as the most appropriatedispensing points for more vulnerable patients whorequire greater monitoring and supervision [6]. Asclients of clinics are more likely to be functioning atpoorer levels than those dosed at a pharmacy, this pro-vides the most likely explanation for the poorer retentionin the clinic group.

Retention was initially better for those first treated in acorrectional facility but after 9 months, on average,retention was lower. The NSW state prison methadoneprogramme commenced in 1986 and has expanded sincethat time [20]. The interaction between time and firsttreatment in a correctional facility probably reflects thelength of sentence and supervision levels, with the risk ofleaving treatment increasing immediately after releasefrom prison. The immediate post-release period has beenshown to be a period of critical overdose risk, particularlyfor those who cease ORT [21].

Retention in treatment 2001–06

Among clients who commenced treatment between2001 and 2006, those who commenced on buprenor-phine were more likely to leave their first treatmentepisode than those who commenced on methadone. Thislower retention in buprenorphine has been shown incontrolled-trial research [5,22,23]. The recently updatedCochrane Review [5] of clinical trials found that reten-tion rates while in methadone treatment were signifi-cantly better than while in buprenorphine treatment inflexible-dose trials and low-dose trials. For medium-dosetrials, two trials found methadone had better retention,and four others found no significant differences. A recentflexible-dose clinical trial from Germany found no signifi-cant difference in retention over 26 weeks [24]. We alsofound that clients who commenced their first treatment

episode on buprenorphine were more likely to have mul-tiple treatment episodes, and switch medications moreoften. There is a risk that switching from methadone tobuprenorphine may precipitate withdrawal, so this mayexplain the higher rates of switching for those who com-mence on buprenorphine [6]. Also, drug users area heterogeneous group with differing treatment needs.Although buprenorphine was associated with poorerretention in the first episode, as a partial agonist/antagonist it is the preferable option when consideringoverdose risk.

Induction to methadone and buprenorphine involvestitrating dosage level until a therapeutic dose is reached.One explanation for lower retention in first treatmentepisode when treated with buprenorphine may be thatthe average first dose of buprenorphine in the naturalsetting was lower than the equivalent dose for metha-done, and hence less therapeutic for a subgroup ofclients. However, treatment guidelines indicate thatbuprenorphine dose can be increased at a greater ratethan methadone dose [6], so this is unlikely. Previousstudies of routine Australian prescribing doses havefound estimated average doses of 70 mg/day for metha-done and 12 mg/day for buprenorphine [25,26], bothof which are at the lower end of the recommendedrange [6].

Alternatively, it may be that the length of timebetween buprenorphine doses for first episodes is greaterthan necessary, producing withdrawal and craving.Further work is required at the population level to deter-mine the subgroup of clients for whom buprenorphineproves most effective and the point in the treatmentregime when this occurs (which may not be in first epi-sodes for all new clients).

Study limitations

In interpreting these findings, it should be noted that thePharmaceutical Drugs of Addiction Database was notdesigned for epidemiological analysis, but as an adminis-trative database. For this reason there are some limita-tions to the present study. A major constraint was the lackof reliable information on methadone dosage or treat-ment policies in clinics. These are critical factors affectingboth retention and outcomes. There were also no vari-ables such as clinic policies, client treatment programmesother than pharmacotherapy, client income, other druguse during treatment and co-morbidity. The aim of thestudy, however, was to describe treatment retention andits relationship to patient characteristics under condi-tions of routine clinical practice.

There were a number of data entry issues that alsorequire consideration. A small number of ‘new entrants’to the programme in 1985–2006 may have had a previ-



ous treatment episode between 1980 and 1985. Patientswere excluded from this count (and from all analyses) ifthey were on a temporary programme (usually tempo-rary interstate transfers), part of a clinical trial, wererecorded as not having commenced their programme inthe ‘reason for leaving’ field in the database, or wererecorded as completing their programme on the same daythat they were supposed to commence. There were also asmall number of cases (n = 40) where their only treat-ment programme had an exit date prior to the entry date.These were removed from the analysis.

CONCLUSIONS

In sum, we found that patterns of ORT in NSW havechanged over time, with fewer new clients registering intreatment. The profile of those in treatment is now one ofolder users with a long treatment history, reflectingperhaps the lack of attraction for younger users of ahighly risky life-style involved in purchasing and usingheroin and engaging in criminal behaviours to fund suchuse. This study has provided population-level evidence tosuggest that retention in methadone and buprenorphinediffer in routine clinical practice. Future work mightinvestigate ways in which patient adherence and reten-tion may be improved.

Conflicts of interest

Louisa Degenhardt has been provided with funding byReckitt Benckiser in the form of an untied educationalgrant to monitor the extent of injection ofbuprenorphine–naloxone injection after its introductionin Australia and to compare this with the injection ofother OST forms. James Bell has received researchfunding from Reckitt Benckiser for conduct of clinicaltrials, and has been sponsored to attend conferences byReckitt Benckiser and Schering Plough.

Acknowledgements

The National Drug and Alcohol Research Centre andthe National Centre in HIV Epidemiology and ClinicalResearch is funded by the Australian GovernmentDepartment of Health and Aging, and is affiliated withthe Faculty of Medicine at the University of New SouthWales. This study is funded through the National Healthand Medical Research Centre project grant 455451.Louisa Degenhardt is supported by a NHMRC SeniorResearch Fellowship (ID #510279). Tony Butler is sup-ported by a NHMRC Career Award (ID #:350992). Wealso wish thank Ms Pia Salmalanien of the Pharmaceu-tical Services Branch, NSW Health, for her assistancewith data extraction and interpretation.

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Opioid agonist pharmacotherapy in New South Wales from 1985 to 2006: patient characteristics and patterns and predictors of treatment retention