Introduction

Offenders as a socially excluded group of people demonstrate significant drug use and subsequent health problems. Studies investigating the prevalence of drug dependence in UK prisons report variable figures of 10% (Gunn et al., 1991), 39% (Brooke et al., 1996) and 33% (Mason et al., 1997). In a review article, the estimated prevalence of drug abuse among male and female prisoners was estimated to be 10 to 48% and 30 to 60%, respectively (Fazel et al., 2006). A recent survey carried out on the Swedish criminal justice system found that 70% of all individuals had substance abuse problems (including alcohol, drugs or both), with a slightly lower percentage among females compared with the whole group (67%) (Klientkartlaggningen, 2015). These numbers can be compared with the general population in Sweden where 1% of all men and 0.5% of all women fulfil the criteria for drug dependence or abuse (Ramstedt et al., 2013). Similar trends have been reported elsewhere. In France, 30% of prison inmates are heroin addicted, and in Australia, 59% of prison inmates report injecting (primarily heroin) drug use histories. In 2018 in the USA, an estimated 6,410,000 persons were held in prisons or jails, or were on probation or parole (Maruschak and Minton, 2020). Of the prison population, 85% are likely to have an active substance use disorder or were incarcerated for a crime involving drugs or drug use according to the US National Institute on Drug Abuse (National Institute on Drug Abuse (NIDA), 2020). In the US, it is recognised that many offenders need treatment to tackle their drug use (Lo and Stephens, 2000). The link between drug use, subsequent health, social and criminological consequences is well documented in the literature (Michel and Maguet, 2005), and offenders have a high risk of death from opioid overdose within 2 weeks of release from prison (Binswanger et al., 2007, Bird and Hutchinson, 2003, Kinner et al., 2013, Merrall et al., 2010). Substance use disorders are linked to criminal behaviour and are a significant burden on the criminal justice system. Approximately 30% of acquisitive crime is committed by individuals supporting drug use with the use of criminal acts (Magura et al., 1995).

Internationally, methadone maintenance has been the primary choice for chronic opioid dependence in prisons and jails, including those in the Netherlands, Australia, Spain and Canada. As a result, it is increasingly implemented in the criminal justice setting (Moller et al., 2007, Stallwitz and Stover, 2007) with the exception of the US which has not generally endorsed the use of methadone treatment. For example, of the 30,000 individuals a year who enter prison or jail nearly 90% of those receiving prescribed methadone are forced to stop or taper off this treatment (Fiscella et al., 2004. Reasons for this lack of expansion suggest that public opinion and that of the criminal justice system providers consider methadone treatment as substituting one addiction for another. In contrast, buprenorphine appears not to carry the same social stigma associated with methadone treatment and has been used in France, Austria and Puerto Rico (Catania, 2003, Garcia et al., 2007, Gordon et al., 2017, Reynaud-Maurupt et al., 2005). This is noted because unlike methadone it can be administered on alternate days, a feature that would make buprenorphine use more efficient in correctional settings than methadone (Garcia et al., 2007). Naltrexone treatment has shown some promising findings, but associated problems surrounding high attrition and low medication compliance in the community and high mortality rates pose concerns (Gibson and Degenhardt, 2007, Minozzi et al., 2011). In 2005 naloxone was added to the UK’s exempt list of prescription-only medicines that could be administered to save life in an emergency to reverse heroin/opioid overdose (Strang et al., 2006). Use of extended-release naltrexone may also be appealing and beneficial to people who are unlikely to access opioid-agonist maintenance treatment or who prefer a relapse-prevention treatment (Lee et al., 2016). Trials conducted in the criminal justice setting are still lacking, and continuity of care is considered crucial in the treatment of drug-using offenders who transition between prison and the community.

A growing body of evidence shows the effects of pharmacological interventions for drug use among the general population (see Table 1 for a summary of the evidence). Existing reviews have focused on naltrexone maintenance treatment for opioid dependence (Amato et al., 2005, Lobmaier et al., 2008, Minozzi et al., 2011), the efficacy of methadone (Faggiano et al., 2003, Marsch, 1998, Mattick et al., 2009) and buprenorphine maintenance (Mattick et al., 2009). Recent guidance has been provided from the National Institute for Health and Clinical Excellence (NICE) on evidence-based use of naltrexone, methadone and buprenorphine for the management of opioid dependence (National Institute for Health and Care Excellence (NICE), 2007a, National Institute for Health and Care Excellence (NICE), 2007b, National Institute for Health and Care Excellence (NICE), 2019). Five Cochrane reviews (including 52 studies) reported on the effectiveness of opiate methadone therapies (Amato et al., 2005). Findings showed that methadone maintenance therapies at appropriate doses were most effective in retaining participants in treatment and in suppressing heroin use, but evidence of effectiveness for other relevant outcome measures such as criminal activity was weak and was not systematically evaluated. Naloxone use is also found to work in a similar manner by blocking the euphoria (reinforcement) sought by the user and thereby reducing the drug-seeking behaviour and diminishing the risk of physical dependence of heroin use (Kurland et al., 1975). Extended-release naltrexone uses the same mechanism as naloxone but gradually releases a sufficient amount to block the euphoria up to 1 month after an injection (Lee et al., 2016).

Table 1 Evidence on pharmacological interventions in the general population
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Systematic reviews evaluating treatment programmes for offender populations have focused on evaluating treatments in one setting such as community-based programmes (Mitchell et al., 2012a, Mitchell et al., 2012b), or have based their evidence on literature from one country (Chanhatasilpa et al., 2000, Egg et al., 2000), or a number of specific treatments (Mitchell et al., 2006). Pharmacological systematic reviews of offender treatment appear to be sparse. We identified two previous reviews: one focusing on specific drug- and property-related criminal behaviours in methadone maintenance treatment (Marsch, 1998), and one an evaluation of the effectiveness of opioid maintenance treatment (OMT) in prison and post release (Hedrich et al., 2012). The latter of these two reviews identified six experimental studies up until January 2011 (Hedrich et al., 2012). The authors found that OMT in prison was significantly associated with reduced heroin use, injecting and syringe sharing. The use of pre-release OMT was also found to have important implications for associated treatment uptake after release, but the impact on criminal activity was equivocal. Similar findings have been shown with the use of extended-release naltrexone (XR-NTX) which showed that use of XR-NTX before release might reduce opioid overdose, increase abstinence and antagonist medication coverage during the high-risk initial weeks after release in comparison with referral for XR-NTX treatment in the community after release (Friedmann et al., 2018).

Many people under the care of the criminal justice system have a drug misuse problem (Fazel et al., 2015). Whilst previous research has evaluated treatment programmes for offenders more broadly, we know little about the challenges, treatment and rehabilitation opportunities for offenders with pharmacological interventions aimed at reducing drug use and criminal activity. This includes consideration of when and where to offer treatment along the criminal justice pathway to maximise scarce resources and maximise the effectiveness of treatment. We therefore believe that a systematic review evaluating existing evidence from randomised controlled trials (RCTs) might be helpful in identifying treatments for reducing drug use and criminal activity in this vulnerable population. In principle, the RCT design eliminates the threat to internal validity providing there is a sufficiently large number of units assigned as the experimental and control conditions and methods to reduce bias are implemented (Weisburd, 2010).

Given the importance of relating economic cost to a reduction in drug use and related offending behaviour, good-quality economic evidence will help inform strategies which represent the best use of limited resource (Higgins and Green, 2011). In this review, we use the Drummond checklist (Drummond et al., 2005) to evaluate and document the availability of resource information within the studies. The Drummond checklist is a widely used tool to assess the quality of economic evaluation studies. It assesses whether the study has a well-defined question, describes the competing programmes, provides information on the effectiveness of the programmes, presents all of the important and relevant costs and consequences for each programmes and assesses whether costs and consequences of the programmes were accurately measured and assigned credible values (and discounted appropriately). The checklist also assesses any incremental cost-effectiveness analysis and sensitivity analysis around the costs and consequences.

This systematic review has five primary research questions: (1) Do pharmacological treatments for drug-using offenders reduce drug use? (2) Do pharmacological treatments for drug-using offenders reduce criminal activity? (3) Does the treatment setting (e.g. court, community, prison/secure establishment) affect outcome(s) of pharmacological treatments? (4) Does one type of pharmacological treatment perform better than one other? (5) What are the comparative costs and cost-effectiveness of the available interventions?

The systematic review was guided by a protocol which followed Cochrane approaches (Higgins and Green, 2011) to producing systematic reviews and an earlier version has been published as a Cochrane review (Perry et al., 2015).

Methods

Studies included in the review had to meet a number of different criteria including the study design, the type of participants and type of interventions. Studies had to report pre-specified outcome measures to avoid the possibility of any subsequent bias in choosing outcomes. The eligibility criteria are summarised below and described in detail in Table 2.

Table 2 Summary of eligibility criteria
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Studies of illicit drug-using offenders were included in the review regardless of the gender, age, psychiatric history or ethnicity of the study participants. Eligible interventions were those designed, wholly or in part, to eliminate or prevent relapse to drug use or criminal activity, or both, among participants. We defined relapse as individuals who may have returned to an incarcerated setting, or had subsequently been arrested or had relapsed back into drug misuse, or both. The primary outcomes investigated in the review were drug use (self-reported drug use measures and biological drug use measures), self-reported or official report of criminal activity (dichotomous and continuous data for arrests, reincarceration and parole violations) and adverse effects. Secondary outcomes were resource use, costs and cost-effectiveness related to the interventions, health care activity, criminal activity and productivity. Randomised controlled trials (RCTs) were the eligible study design and no date or language limits were applied to this review.

Search strategy for identification studies

The original searches for this review are reported in Perry (Perry et al., 2006, Perry et al., 2015) and were subsequently updated in January 2018 to cover the period 2014 to 2018 and then updated further again in February 2019 to cover the period 2018 to 2019. We searched 12 databases: ASSIA, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Criminal Justice Abstracts, Embase, Health Management Information Consortium (HMIC), LILACS, MEDLINE, PAIS, PsycINFO, Science Citation Index and Social Science Citation Index. The full search strategies for each database are included in the Appendix.

To identify economic studies the topic specific searches of nine databases (ASSIA, CENTRAL, CINAHL, Criminal Justice Abstracts, HMIC, LILACS, PAIS, Science Citation Index, Social Science Citation Index) would have identified all potential RCTs and economic evaluations included in the review. For the Embase, MEDLINE and PsycINFO databases the search strategy incorporated an RCT filter to manage the number of identified and relevant citations. This approach may have excluded potential economic evaluations identified from these three databases and is therefore a limitation of the review.

We developed individual search strategies for each database and made use of any controlled vocabulary available for each database. We combined the subject search terms with methodological search filters designed to identify RCTs, where available. Additional search approaches were employed including checking the reference lists of all retrieved articles for further references, searching catalogues of relevant organisations and contacting experts to obtain recommendations of other published or unpublished studies relevant to the review. All references were managed in EndNote (Clarivate, 2020) and subsequently Covidence (Veritas Health Innovation, 2013) software.

Screening and coding process

A team of reviewers independently inspected the titles and abstracts for potential inclusion in the review. Each record was assessed by two reviewers. The full articles were obtained for each record which seemed likely to be eligible and the full text was assessed for eligibility by two reviewers independently. In the case of disagreement, a third independent reviewer helped to arbitrate. The screening criteria are provided in the Appendix.

We used data extraction forms to standardise the reporting of data from all studies obtained as potentially relevant. Two reviewers independently extracted data and subsequently checked them for agreement. The narrative tables included a presentation of the study details (e.g. author, year of publication and country of study origin), study methods (e.g. random assignment), participants (e.g. number in sample, age, gender and ethnicity), interventions (e.g. description, duration, intensity and setting), outcomes (e.g. description, follow-up period and reporting mechanism) and notes (e.g. country and funding).

Measures of treatment effect

Studies were combined as mean differences (MD) with 95% confidence intervals in the meta-analyses for continuous outcomes measured on the same scale and standardised mean difference (SMD) for outcomes measured on different scales. Higher scores for continuous measures are representative of greater harm. We present dichotomous outcomes as risk ratios (RR), with 95% confidence intervals (CIs).

Statistical issues

To avoid double counting of outcome measures (e.g. arrest and parole violation) and follow-up time periods (e.g. 12, 18 months), we checked all trials to ensure that multiple studies reporting the same evaluation did not contribute towards multiple estimates of programme effectiveness. We followed Cochrane guidance and we combined intervention and control groups to create a single pair-wise comparison. Where this was not appropriate we selected one treatment arm and excluded the others. We attempted to contact the study authors via email where missing data occurred in the original publication.

We assessed heterogeneity using the I2 statistic and Chi2 statistic (Higgins and Green, 2011). We regarded heterogeneity as substantial if the I2 was greater than 50% or the p value was lower than 0.10 for the Chi2 test for heterogeneity (Deeks et al., 2017). Following specific Cochrane guidance (Deeks et al., 2017), we distinguished the following values to denote no important, moderate, substantial and considerable heterogeneity, respectively: 0 to 40%, 30 to 60%, 50 to 90% and 75 to 100%.

Risk of bias assessment

The review team assessed risk of bias in all included studies using risk of bias assessment criteria recommended in the Cochrane Handbook (Higgins and Green, 2011). Further detail on risk of bias assessment is provided in the Appendix.

Data synthesis

The Revman software package (The Nordic Cochrane Centre (The Cochrane Collaboration), 2014) was used to perform a series of meta-analyses for continuous and dichotomous outcome measures. A random effects model was used to account for participants coming from different underlying populations. We used the transformations as laid down by the Cochrane Handbook (Higgins and Green, 2011) for continuous outcomes. For conversions of standard error into standard deviations and the calculation of standard deviations calculated from 95% confidence intervals (CIs) we used the standard equations set out in Fig. 1.

Fig. 1
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Statistical treatment

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Economic appraisal

Economic or resource use information was assessed using the Drummond classification scheme (see Appendix) (Drummond et al., 2005). This criterion was applied by an economist to indicate the costs and the consequences of the intervention(s) relevant to various public sectors. These included healthcare, criminality, labour force participation or other public goods. According to Drummond, studies containing information on the economics of the intervention can be classified as full economic evaluation studies or partial economic evaluation studies (Drummond et al., 2005). A full economic evaluation is a comparative analysis of two or more interventions in terms of both resource use (or costs) and outcomes (or consequences) (Drummond et al., 2005). Full economic evaluations can be further classified as cost-benefit analysis, cost-effectiveness analysis and cost-utility analysis based on consequences measured in monetary units, physical units (e.g. mortality) and utilities (e.g. quality-adjusted life years (QALYs)), respectively. Evaluations that are not comparative or do not consider both costs and consequences are classified as partial evaluations (e.g. cost-outcome description or cost analysis). Studies containing economic information using the Drummond criteria were identified, and information related to resource use and perspectives were recorded.

Search results

Searches for this review were first conducted in Perry (Perry et al., 2006, Perry et al., 2015) and were last updated in February 2019. The searches identified a total of 16,786 records and 988 additional records were identified from other sources. Following deduplication, 9657 records were screened using information in the title and abstract. Of these, 9406 records were excluded. We acquired the remaining 251 full papers for assessment and excluded 237 of these. A total of 22 studies were finally deemed eligible for the review and were included in the qualitative synthesis, with 19 of them included in the meta-analyses. The 22 included studies randomised 4372 participants from research published between 1969 and 2019. Fig. 2 shows the PRISMA flow diagram of the numbers of records included and excluded at each stage of the selection process.

Fig. 2
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PRISMA flow diagram

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Fourteen of the 22 trials were conducted in the US and three in the UK. The other 5 studies were conducted in Iran, Australia, Norway, Sweden and Mexico. Twenty-one of the 22 studies included male adult drug-using offenders and 1 study recruited only female participants (Cropsey et al., 2011). In 2 studies, the percentage of each gender was not reported (Kurland et al., 1975, Wright et al., 2011).

The age of study participants ranged from 17 to 55 years. In 7/22 (32%) studies, the majority of participants were of white ethnic origin. The studies were divided by setting into community (n = 9) (Brodie et al., 2009, Brown et al., 2013, Cornish et al., 1997, Coviello et al., 2010, Cropsey et al., 2011, Hanlon et al., 1975, Hanlon et al., 1977, Kurland et al., 1975, Lee et al., 2016), prison (n = 7) (Bayanzadeh, 2004, Dolan et al., 2003, Dole et al., 1969, Howells et al., 2002, Lobmaier et al., 2010, Rich et al., 2015, Wright et al., 2011) and those that started in a secure setting and continued into the community (n = 6) (Kinlock et al., 2005, Kinlock et al., 2007, Konstenius et al., 2014, Magura et al., 2009, McKenzie et al., 2012, Parmar et al., 2017).

Fifteen of the 22 trials evaluated outcomes at 6 months or less, 4 trials reported outcomes up to 12 months (Brown et al., 2013, Dole et al., 1969, Kinlock et al., 2007), 1 study reported outcomes at 18 months (Lee et al., 2015) and 1 reported outcomes at 4 years (Dolan et al., 2003).

Different outcome measures were presented for each study, and just over half of all studies reported 4 or more outcome measures. One study reported on criminal activity only (Cornish et al., 1997) and 8 trials reported on drug use only (Bayanzadeh, 2004, Brown et al., 2013, Cropsey et al., 2011, Dolan et al., 2003, Hanlon et al., 1977, Konstenius et al., 2014, Wright et al., 2011). Six studies did not report any information on adverse events, side effects from the drug or drug safety (Bayanzadeh, 2004, Dolan et al., 2003, Dole et al., 1969, Hanlon et al., 1975, Hanlon et al., 1977, Kurland et al., 1975). Three studies referred to the measurement of adverse events but did not report them (Coviello et al., 2010, Cropsey et al., 2011, Wright et al., 2011). 4 studies reported resource and cost information (Magura et al., 2009, Murphy et al., 2017, Rich et al., 2015, Warren et al., 2006).

Overview of studies

Meta-analyses

Nineteen of the 22 studies provided data to potentially be included in 1 or more meta-analyses. The interventions report on agonistic pharmacological interventions (buprenorphine, methadone) and antagonistic pharmacological interventions (naltrexone and naloxone) compared with no intervention, other non-pharmacological treatments (e.g. counselling) and other pharmacological drugs (vigabatrin and cyclazocine). The comparisons are shown in Table 3 and in Fig. 3.

Table 3 Meta-analysis results by comparison and outcome
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Fig. 3
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Forest plots of intervention effects

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Agonist (methadone) versus no intervention (placebo or waiting list control)

Two studies (237 participants) (Cropsey et al., 2011, Dolan et al., 2003) showed no significant reduction in drug use using biological measures (RR 0.74, 95% CI 0.53 to 1.02) and three studies (317 participants) showed no significant reduction in self-reported drug use (RR 0.61, 95% CI 0.31 to 1.18) (Cropsey et al., 2011, Dolan et al., 2003, Dole et al., 1969). Two studies (304 participants) showed a significant reduction in self-reported drug use (SMD − 0.57, 95% CI − 0.80 to − 0.34) (Dolan et al., 2003, Kinlock et al., 2005). For criminal activity, one study (62 participants) showed no significant reduction in re-arrests (RR 0.60, 95% CI 0.32 to 1.14) (Kinlock et al., 2005). Three studies (472 participants) showed no significant reduction in reincarceration (RR 0.77, 95% CI 0.36 to 1.64) (Dolan et al., 2003, Dole et al., 1969, Kinlock et al., 2005) and one study (51 participants) showed a significant reduction in criminal activity (MD − 74.21, 95% CI − 133.53 to − 14.89) (Kinlock et al., 2005).

Agonist (methadone) versus partial agonist (buprenorphine)

Two studies (370 participants) showed no significant reduction in self-reported drug use (RR 1.04, 95% CI 0.69 to 1.55) (Magura et al., 2009, Wright et al., 2011). One study (81 participants) showed no significant reduction in self-reported drug use (MD 0.70, 95% CI − 5.33 to 6.73) (Magura et al., 2009). One study (116 participants) showed no significant reduction in criminal activity (RR 1.25, 95% CI 0.83 to 1.88) (Magura et al., 2009).

Agonist (methadone) versus antagonist (naltrexone)

A single study (44 participants) showed no significant reduction in self-reported drug use (MD 4.60, 95% CI − 3.54 to 12.74) and showed no significant reduction in dichotomous (RR 1.10, 95% CI 0.37 to 3.26) or continuous measures of reincarceration (MD − 0.50, 95% CI − 8.04 to 7.04) (Lobmaier et al., 2010).

Agonist (methadone) and non-pharmacological intervention versus non-pharmacological intervention

Two studies (203 participants) showed no significant reduction in self-reported drug use (RR 0.39, 95% CI 0.14 to 1.13) (Bayanzadeh, 2004, Kinlock et al., 2007).

Agonist (vigabatrin) versus placebo

One study (103 participants) showed no evidence of a difference in terms of the number of negative urine tests for cocaine (MD 2.1, 95% CI − 0.34 to 4.54) and end of trial abstinence for marijuana (RR 0.64, 95% CI 0.16 to 2.52) but showed evidence of a difference in the end of trial abstinence (RR 1.06, 95% CI 0.28 to 4.01) and 4-week abstinence for cocaine (RR 6.36, 95% CI 1.50 to 27.01) (Bayanzadeh, 2004, Brodie et al., 2009, Kinlock et al., 2007).

Antagonist (naloxone) versus no intervention (placebo or waiting list control)

Three studies (333 participants) showed no significant reduction in self-reported drug use (RR 1.06, 95% CI 0.87 to 1.28) (Hanlon et al., 1975, Hanlon et al., 1977, Parmar et al., 2017).

Antagonist (naltrexone) versus non-pharmacological treatment

Two studies (371 participants) showed a significant reduction in subsequent opioid use (RR 0.60, 95% CI 0.44 to 0.81) (Coviello et al., 2010, Lee et al., 2016). Two studies (371 participants) showed no significant reduction in cocaine use (RR 1.24, 95% CI 0.54 to 2.84) (Coviello et al., 2010, Lee et al., 2016). Three studies (422 participants) showed a significant reduction in subsequent reincarceration (RR 0.55, 95% CI 0.31 to 0.99) (Cornish et al., 1997, Coviello et al., 2010, Lee et al., 2016). One study (63 participants) showed no significant reduction in subsequent drug charges (RR 3.10, 95% CI 0.34 to 28.19) (Coviello et al., 2010).

Mixed antagonist and agonist (cyclazocine) versus antagonist (naloxone)

One study (70 participants) showed no significant reduction in abstinence at 6 months comparing mixed antagonist and agonist (cyclazocine) with the antagonist naloxone (RR 1.14, 95% CI 0.46 to 2.81) (Hanlon et al., 1975).

Agonist (methadone) versus forced tapered withdrawal from methadone

One study (283 participants) explored continued use of methadone within a prison setting compared with forced tapered withdrawal of methadone (Rich et al., 2015). The study found no significant difference in reduction in any drug use at 1 month following release from prison (RR 1.05, 95% CI 0.83 to 1.34), opioid use at 1 month following release (RR 0.56, 95% CI 0.26 to 1.22) or use of injectable illegal drugs (RR 0.67, 95% CI 0.40 to 1.15) (Rich et al., 2015). The study also found no difference between the two options in terms of reincarceration at 1 month post release from prison (RR 1.49, 95% CI 0.63 to 3.53) (Rich et al., 2015).

Agonist (methadone) prior to release with financial support versus agonist (methadone) on release with no financial support

One study (46 participants) explored the impact of providing financial support for methadone treatment following release from prison compared with no financial support on drug outcomes and criminal justice outcomes (McKenzie et al., 2012). The study found no significant difference between the two options in terms of heroin use in the past 30 days (RR 0.46, 96% CI 0.20 to 1.03), use of other opiates in the past 30 days (RR 0.12, 95% CI 0.01 to 2.22), use of crack/cocaine in the past 30 days (RR 0.46, 95% CI 0.20 to 1.03), marijuana use in the past 30 days (RR 0.42, 95% CI 0.09 to 2.07), polydrug use in the past 30 days (RR 0.70, 95% CI 0.38 to 1.28) or any drug injecting in the past 30 days (RR 0.32, 95% CI 0.10 to 1.04) (McKenzie et al., 2012). The study reported no significant difference between the interventions for reincarceration (RR 0.42, 95% CI 0.09, 2.07) or arrest within the past 6 months (RR 1.26, 95% CI 0.54, 2.96) (McKenzie et al., 2012).

Narrative findings

Narrative findings were presented for three studies where suitable data for extraction and exclusion in the meta-analysis were not available. One study compared methylphenidate or placebo to a non-pharmacological intervention (Konstenius et al., 2014). In this study, male participants with attention deficit disorder receiving methylphenidate had a higher proportion of drug negative urine test results compared with the placebo group (p = 0.047). A second study compared a specialist facility for treatment of methadone versus primary care plus suboxone (buprenorphine and naloxone) versus a specialist facility for suboxone treatment (Brown et al., 2013). At 6 months, the authors reported no use of opioids in any of the randomised groups (total of 15 participants). The final study compared methadone and placebo versus lofexidine and placebo (Howells et al., 2002). The authors reported no statistical reduction in the amount (p = 0.36) or intensity (p = 0.46) of opioid (heroin) use in the last month.

Adverse events

Seven of the 22 (32%) studies did not report any information on adverse events, side effects of drugs nor referred to drug safety (Bayanzadeh, 2004, Brown et al., 2013, Dolan et al., 2003, Dole et al., 1969, Hanlon et al., 1975, Hanlon et al., 1977, Kurland et al., 1975). Three (3/22, 14%) studies measured adverse events, but did not report the findings (Coviello et al., 2010, Cropsey et al., 2011, Wright et al., 2011). Forty-one percent of the studies (9/22) reported only mild or moderate adverse events (Brodie et al., 2009, Cornish et al., 1997, Howells et al., 2002, Kinlock et al., 2005, Konstenius et al., 2014, Lee et al., 2016, Lobmaier et al., 2010, Magura et al., 2009, Parmar et al., 2017). One study reported 10 serious adverse events including nine hospitalisations (Kinlock et al., 2007). The hospitalisations included two cases for heart disease and one each for pneumonia, alcohol detoxification, kidney disease, high blood pressure, psychiatric problems and back pain (Kinlock et al., 2007). Two studies reported a fatal overdose (Kinlock et al., 2007, Rich et al., 2015) and one study reported two fatal overdoses (McKenzie et al., 2012).

Economic outcomes

The economic appraisal using the Drummond criteria identified four studies reporting some cost information (Magura et al., 2009, Murphy et al., 2017, Rich et al., 2015, Warren et al., 2006). Table 4 shows the results of the type of resource costs described for each paper. Three of the four studies were full economic evaluations reporting both incremental costs and outcomes (Magura et al., 2009, Murphy et al., 2017, Warren et al., 2006).

Table 4 Available economic information (resource use and/or cost) and evaluation type according to Drummond classification scheme (see Appendix)
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In terms of the overall Drummond classification (Drummond et al., 2005), three studies were coded as 4 (a full economic evaluation) and one study was coded as 3 (partial economic evaluation).

The Magura 2009 (Magura et al., 2009) study noted differences in the costs of administering buprenorphine and methadone, but were not sufficient for us to conduct a full cost-effectiveness appraisal. The investigators estimated that about ten times as many inmates can be served with methadone as with buprenorphine with the same staff resources. This cost implication is also endorsed in the community, where physicians have difficulty in obtaining reimbursement for buprenorphine treatment for released inmates, making the continued use of buprenorphine problematic after release.

The Murphy 2017 (Murphy et al., 2017) study conducted a full economic analysis reporting incremental cost-effectiveness ratios (ICERs), costs, QALYs and abstinent years of using extended-release naltrexone (XR-NTX) compared with treatment as usual (TAU) at 25 weeks and 78 weeks, respectively. The 25-week ICERs were reported as $162,150/QALY and $46,329/ abstinent year. The ICER values at 78 weeks were $76,400/QALY and $16,371/abstinent year. The study reported that XR-NTX was effective in increasing both QALYs and abstinence rates compared with TAU. However, it was not cost-effective at the normally accepted threshold levels in the US, primarily due to the high price of the injection.

The Warren 2006 (Warren et al., 2006) study estimated the cost-effectiveness of the New South Wales (NSW) prison methadone programme compared with no methadone program. The study reported the annual cost of providing prison methadone in NSW as AUD$2.9million (or AUD$3234 per inmate per year) and the ICER as AUD $38 per additional heroin-free day. It also reported that prison methadone is not costlier than community methadone, and it reduces morbidity and mortality through decreasing heroin use in prisons.

The final study by Rich 2015 (Rich et al., 2015) reported, as a secondary outcome, on healthcare costs (per inmate) associated with continued methadone maintenance-treatment programme compared with usual care (i.e. forced withdrawal from methadone) at 1 month after release from incarceration. Continued methadone treatment resulted in higher (methadone) treatment cost per individual compared with forced withdrawal ($362 vs $225, p < 0.001). The additional treatment costs were offset by savings incurred by reduced cost for physician ($6.60 vs $8.80, p = 0.793) and medical care ($211 vs $372, p = 0.894) after release, resulting in lower total costs ($609 vs $637, p < 0.001). Continued methadone treatment also resulted in a greater probability of attendance at a methadone clinic after release and was more effective than forced withdrawal.

Risk of bias assessment

Although all the included studies were randomised trials, the level of reporting was uneven and many had unclear or high risk of bias for at least one element of the risk of bias assessment. Nearly 50% were rated as unclear risk of bias in terms of random sequence generation and over 50% of the trials were rated as unclear in terms of allocation concealment. 32% (7/22) of the studies were rated as low risk of bias for participant and personnel blinding and 82% (18/22) were rated as unclear on both subjective and objective measures of detection bias. Over 75% of the trials were at high risk of bias because they did not report all of the outcome data they set out to collect. Over 50% of the studies were rated at low risk for selective reporting. The overall risk of bias judgements of the included studies are shown in Fig. 4, and summary and detailed accounts of the risk of bias assessment can be found in the Appendix.

Fig. 4
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Risk of bias judgements

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Conclusions

The results of this systematic review provide some evidence to answer our original review questions. The review identified that we have some evidence to suggest that pharmacological interventions are effective in reducing drug use and criminal activity (Perry et al., 2015). The updated review revealed a total of 22 trials involving 4372 participants. The 22 trials compared pharmacological interventions or compared pharmacological interventions to no intervention and/or a placebo. Most studies were conducted in the USA, with the majority involving male adult offenders. The updated meta-analyses included 19/22 quantitative studies. Ten different pharmacological drugs were evaluated including methadone, buprenorphine, naltrexone, methylphenidate, vigabatrin, suboxone, naloxone, lofexifine, naltrexone and cyclazocine. Methadone in comparison with no treatment was the only comparison to demonstrate a significant reduction in subsequent drug use (using biological measures), self-reported drug use (using continuous measures) and criminal activity. When compared with methadone, no significant differences were found for buprenorphine, naltrexone or suboxone. None of these studies identified a significant reduction in either criminal activity and/or drug use. One study comparing buprenorphine to placebo (Cropsey et al., 2011) was the only study to involve wholly female offenders. More pharmacological trials of female offenders are required to identify comparability between men and women.

Studies of naloxone and methylphenidate in comparison with a placebo and non-pharmacological intervention, respectively, showed no significant differences for self-reported drug use. The evidence supporting the use of naloxone was explored using two very old studies (Hanlon et al., 1977, Hanlon et al., 1975) and one more recent study that had to be halted early due to problems with the randomisation procedure (Parmar et al., 2017). Naltrexone in comparison with a non-pharmacological intervention showed a significant reduction in self-reported drug use and reincarceration. The use of extended naltrexone pre and post prison release has produced some promising results, finding no overdoses during the treatment process (Lee et al., 2016). This study also reported that use of extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment at 24 weeks, but later comparisons (at 52 and 78 weeks) found no difference between the use of extended-release naltrexone and use of a brief counselling intervention (Lee et al., 2016). One study investigated methadone continuation treatment compared with forced tapered withdrawal from methadone within a prison setting, but found no significant difference in the reduction of any drug use at 1 month following release (Rich et al., 2015). The study also found no difference between the treatment options where reincarceration occurred at 1 month post release from prison. The impact of providing financial support for methadone treatment following release from prison was compared with no financial support in one study, but no significant difference was observed in terms of drug use or criminal justice outcomes (McKenzie et al., 2012). The study also reported no significant difference between the interventions in relation to arrest or reincarceration at six-month follow-up. We were unable to answer our third review questions about the impact of treatment setting on drug use or criminal activity. This was primarily because of the heterogeneity of the study comparisons and outcome measures. Given the relatively scarce resources for drug treatment evaluation opportunities in this population, future research should seek to build on existing trial data to develop an evidence-base to allow for such comparisons to be made.

The majority of studies included in the review reported only mild to moderate adverse effects, or did not report on drug safety as part of the trial information. One study reported serious adverse effects and three studies reported overdoses. Adverse effects should be measured consistently across any pharmacological drug trial to capture important data about drug safety. The current evidence does not provide a comprehensive overview of drug safety within this population.

Our final review question focused on the comparative costs and cost-effectiveness evidence of using such interventions to reduce drug use and criminal activity. An appraisal of the economic evidence identified studies with costs and outcomes data for pharmacological treatments among drug-using offenders in three studies and costs data in one study. All studies reported data on the direct medical costs associated with the provision of treatment (Magura et al., 2009, Murphy et al., 2017, Rich et al., 2015, Warren et al., 2006) and one study also included costs related to criminal justice (Murphy et al., 2017). The findings from the studies revealed the higher effectiveness of pharmacological treatments in terms of increased QALYs and abstinent years (Murphy et al., 2017) and reduced heroin use (Warren et al., 2006). One study reported methadone to be cost-effective at the current willingness to pay thresholds (Warren et al., 2006). Another study reported continued methadone treatment to dominate forced withdrawal in terms of costs and effects (Rich et al., 2015). More research is needed to compare the relative cost-effectiveness of a range of treatments (pharmacotherapies, non-pharmacological interventions and combined treatments) in prison and community-based criminal justice settings.

Additionally, the studies contained mainly male offenders, with only one study containing a 100% sample of female offenders. The majority of studies were conducted in the USA. Together these factors limit the external validity and generalisability of the study findings. For these reasons, the studies are unlikely to reflect different international practice in the criminal justice system. Besides the limitations already discussed, the search methodology was limited to databases that could be accessed via the University of York and extensive website searches were not conducted. As a result, some literature may have been missed from this updated version. Specific search terms were not used to identify cost and cost-effectiveness studies in 3/12 databases which meant that some economic studies might have been missed from this review.

Several research implications can be identified from this review. Generally, better quality research is required to evaluate the effectiveness of interventions with extended long-term effects of aftercare following release into the community. Buprenorphine research in the prison environment requires evidence of the long-term impact and larger studies; currently, an equivalence of buprenorphine and methadone exists. Future clinical trials should collect information from all sectors of the criminal justice system. This would enhance the heterogeneous nature of the included studies and would facilitate generalisation of study findings. Evidence of comparable mortality rates in prisoners using pharmacological interventions (particularly after release) needs to be explored to assess the long-term outcomes of such treatments, perhaps using alternative study designs to randomised controlled trials. The link between dosage, treatment retention and subsequent criminal activity should be examined across all three pharmacological treatment options. Evidence from other trial data suggests that dose has important implications for retention in treatment; in future studies, this should be considered alongside criminal activity outcomes. Cost and cost-effectiveness information should be standardised within trial evaluations; this will help policymakers to decide upon health versus criminal justice costs.