EFFECTIVE AND COST-EFFECTIVE MEASURES TO REDUCE ALCOHOL MISUSE IN SCOTLAND: AN UPDATE TO THE LITERATURE REVIEW
SECTION NINE: RELAPSE PREVENTION
In the previous review, the main findings relating to the effectiveness and cost-effectiveness evidence of relapse prevention were;
psychosocial interventions can be effective and may almost double the percentage achieving abstinence or controlled drinking compared with spontaneous remission rates;
adjunct use of Acamprosate or Naltrexone has been shown in small trials to reduce relapse rates;
a large US study has shown health care cost savings arising from psychosocial treatments;
studies in Belgium and Germany have demonstrated cost savings for adjunct use of Acamprosate;
two US studies have shown outpatient treatment to be more cost-effective than inpatient treatment;
two small studies on Behavioural Marital Therapy have produced opposite conclusions regarding cost-effectiveness; and
using UK cost data, adjunct treatment with Acamprosate produces net resource savings but this may not result in financial savings.
The additional literature reviewed for this update broadly supports these findings. Additional points of interest are:
no evidence has emerged to support any difference in effectiveness or cost-effectiveness between types of psychosocial intervention;
comparisons of Acamprosate and Naltrexone are confounded by differences in length of follow up and outcomes;
More information is required on the precise content of psychosocial interventions. Savings from reduced future use of health care services need to be interpreted with care.
9.1 Relapse prevention programmes consist of a combination of psychosocial and pharmacological interventions aimed at maintaining abstinence or problem free drinking following detoxification.
EFFECTIVENESS OF RELAPSE PREVENTION
Types of intervention
9.2 The main forms of psychosocial intervention reviewed previously were cognitive-behavioural therapy (CBT), motivational enhancement therapy (MET) and 12-Step Facilitation Therapy (TSF). The current review also found additional evidence relating to Behavioural Self Control Training (BSCT) and Marital or Family Therapy.
9.3 The main forms of pharmacotherapy are Disulfiram (aversion therapy), Naltrexone and Acamprosate. Although Naltrexone and Acamprosate are both classed as anti-craving therapies they work in different ways. Naltrexone blocks the pleasant effects of alcohol, thus reducing the desire to drink and the reinforcing effects of any alcohol consumption. The effect of Acamprosate is currently linked to a reduction in tendency to relapse due to negative craving (negative effect of the absence of alcohol). No additional evidence was found relating to any other form of pharmacotherapy.
Effectiveness of relapse prevention
9.4 Slattery et al (2003) reviewed all psychosocial interventions and found evidence of effectiveness for Coping/Social Skills Training (CSST), Behavioural Self-Control Training (BSCT), MET and Marital or Family Therapy. (CBT, as used in Project Match, was included in Social Skills Training.) The meta analysis results in table 9.1 show significant results for these interventions. The results include data from Project MATCH and are consistent with previous findings. There are no clear differences in the effect sizes of the different treatments.
Table 9.1 Meta-analysis of rates of abstinence or controlled drinking
Intervention95% Confidence Interval
Coping/Social Skills Training
Source: Slattery et al (2003)
9.5 A qualitative review of marital and family interventions also reports evidence of reduced alcohol misuse, as well as better rates of entering treatment and retention in treatment (Thomas and Corcoran 2001).
9.6 The most recent reviews in this area are Slattery et al (2003) and Soyka and Chick (2003). Both of these reviews incorporated material published in other reviews (Kranzler and van Kirk 2001; Streeton and Whelan 2001; Mason 2001). Overman et al (2003) review studies of Acamprosate and include the same studies as the other reviews. Srisurapanont and Jarusuraisin (2003) conducted a Cochrane Review of opioid antagonists and cover mostly the same Naltrexone studies. Additional studies in their review involve dual dependence on cocaine and alcohol, some small studies (n=10 or less in each group) and one study of Nalmefene. Compared with the psychosocial therapies, more studies have been carried out in this area since those included in the previous review (Ludbrook et al 2002).
9.7 The review by Soyka and Chick was restricted to European studies and included 16 published controlled trials of Acamprosate versus placebo. For the 13 studies for which continuous abstinence duration (CAD) could be calculated, all but one (UK) study showed a positive effect for Acamprosate (p<0.05). It is suggested that the lack of effect in the UK study may be due to a delay before treatment following detoxification. The review by Slattery et al included two unpublished studies with negative results but still found Acamprosate to be effective. One study that combined Acamprosate with different psychosocial therapies found no evidence of any significant difference in effect between the various types of psychosocial therapy.
9.8 Both reviews also support the effectiveness of Naltrexone. Soyka and Chick (2003) point out that the results from European studies have been less consistent than the results for Acamprosate. A meta-analysis of eight published trials found a significant improvement in relapse rates but only two of the included studies were European. The only UK trial of Naltrexone concluded that it was only effective in patients who demonstrated good compliance. Two European studies have evaluated Naltrexone in combination with different psychosocial therapies. Those receiving Naltrexone in combination with CBT had significantly fewer days of heavy drinking than those receiving a placebo (12% versus 27%; p<0.05) (Balldin et al 1998; cited in Soyka and Chick 2003). In the second study, Naltrexone increased the percentage never relapsing to heavy drinking in the coping skills group (26% versus 3%; p=0.008) (Heinälä et al 2001; cited in Soyka and Chick 2003). However, in both studies, receiving Naltrexone had no effect within the supportive counselling group. Slattery et al (2003) also concluded that Naltrexone is effective but did not recommend its use in Scotland as Naltrexone did not have a Marketing Authorisation for treatment of alcohol dependence.
9.9 Slattery et al (2003) also reviewed evidence on Disulfiram. The conclusions were similar to the previous review by Ludbrook et al (2002) and no new studies appear to have been carried out in this area.
Comparisons of Acamprosate and Naltrexone
9.10 Kranzler and van Kirk (2001) provide an indirect comparison of Acamprosate and Naltrexone through a meta-analysis of trials of both drugs. They found no statistical difference in the efficacy of the two drugs, based on the comparisons that could be made. Slattery et al (2003) report that the combined success rates (abstinence or controlled drinking at the end of the trial) differ between the two drugs. For Acamprosate versus placebo the combined success rates are 26% versus 18% and for Naltrexone versus placebo the figures are 51% versus 41%. However, there are systematic differences in the primary outcomes and length of follow up, as shown in table 9.2, which may explain these differences. Trials of Acamprosate are more likely to have longer follow up and all but one trial has abstinence as its primary outcome. Streeton and Whelan (2001) also drew attention to the short duration of treatment with Naltrexone (12 weeks) in the trials they reviewed and concluded that the optimal treatment period could not be determined. Two single studies have shown a decline in the effectiveness of Naltrexone in the post treatment period (O'Malley et al 1996; Anton et al 2001).
Table 9. 2 Number of trials by length of follow up and primary outcome.
Months of follow up
8 / 17
9 / 17
16 / 17
1 / 17
10 / 17
4 / 17
3 / 17
11 / 17
Source: Data taken from Slattery et al 2003 Appendix 17
*information not available for 3 trials
9.11 Two single centre studies providing direct comparisons of Acamprosate and Naltrexone were included in the review by Soyka and Chick (2003) (Keifer et al 2003; Rubio et al 2001). Both studies favoured Naltrexone over Acamprosate, on the basis of outcomes of number of heavy drinking days or relapse to heavy drinking (5 or more drinks per day), with one study showing the combined use of both Naltrexone and Acamprosate being most effective (Keifer et al 2003). However, Rubio et al reported no difference in days to first drink. The review authors concluded that, whilst more evidence is required, it appears that Acamprosate is more suited to sustaining abstinence and treatment with Naltrexone may be indicated for patients who cannot or will not abstain (Soyka and Chick 2003). Srisurapanont and Jarusuraisin (2003) conclude that there is too little evidence to support the superiority of Naltrexone over Acamprosate.
9.12 Barrick and Connors (2002) review relapse prevention for older adults and report that CBT is as effective for older adults as for younger age groups. Group and family therapies are beneficial with one study reporting that older adults would prefer separate groups held at a slower pace. Only one pharmacological study specifically considered older adults, with the finding that Naltrexone was well tolerated and efficacious.
9.13 No reviews relating to alternative settings were identified.
9.14 Comparison of providers has not been carried out in any of the studies reviewed.
Intensity of treatment
9.15 One UK study compared a 6 week CBT outpatient programme with a 10 week programme (cohort comparison) (Bamford et al 2003). The shorter programme had higher completion rates mainly due to the shorter period over which attrition could occur. Those who completed either programme had similar outcomes but comparisons for the whole cohort are not presented.
9.16 A statistical analysis of follow up data on individuals recruited at first contact with alcohol treatment services suggests that duration of first treatment improves outcomes at 1 year and 8 years and duration of additional treatment improves outcomes at 8 years (Moos and Moos 2003). Intensity of treatment had no effect. The analysis may have failed to control for selection bias.
9.17 A comparison of substance abuse treatment programmes using CBT or TSF showed that TSF increases the use of self help groups after treatment (Humphreys and Moos 2001). This is shown to reduce the use of formal health care saving $4729 per patient (p<0.001). However, the self help groups are assumed to be costless.
9.18 A study of individual versus group CBT in substance abuse found similar levels of effectiveness (Marques and Formigoni 2001). No formal cost-effectiveness analysis was conducted but the group treatment used less resources.
9.19 The previous review identified two studies that had modelled the cost-effectiveness of Acamprosate. Annemans et al (2000) concluded that Acamprosate was cost saving to the health care provider, yielding average net savings of 22,000 BEF (£3,370) per patient over 24 months. However, the results were sensitive to the probability of relapse and under different conditions may not be cost saving. The authors omitted wider costs (e.g. productivity etc) and also health benefits. Schadlich and Brecht (1998) investigated the incremental cost per additional abstinent alcoholic for adjuvant Acamprosate compared to a standard care baseline and estimated overall cost savings to society of -DM 2602 (£822) per additional abstinent patient.
9.20 This review includes two further studies of Acamprosate. Palmer et al (2000) have also modelled the cost-effectiveness of adjuvant Acamprosate in Germany. The perspective of the study is the third party payer of health care costs and only medical care costs are included. Acamprosate results in a saving per patient of DM 1861 (1996 prices undiscounted; DM 1662 discounted) and an estimated gain of 1.2 life years (undiscounted; 0.52 life years discounted). The authors note that the abstinence rates for Acamprosate were taken from a single study (Sass et al 1996) rather than a review and the odds ratio for treatment effect in this study is higher than that given by meta-analysis in Slattery et al (2003) (2.87 compared with 1.73).
9.21 Rychlik et al (2003) present a comparison based on two prospective cohorts; one receiving standard care and one receiving adjuvant Acamprosate. Whilst this study design does not have the robustness of a randomised approached, the authors are using this design in order to consider whether or not the results achieved under research conditions are reproduced in normal practice. They report highly significant differences in favour of the use of Acamprosate in abstinence rates (0.324 versus 0.204), direct medical care costs (€1224 versus €1543) and total costs (€1592 versus €2004) over one year, based on intention to treat analysis. The follow up rate was 80%. The abstinence effect due to Acamprosate was similar to the levels found in controlled trials.
9.22 A US study of the effect of integrating medical care with substance abuse treatment in an HMO setting, demonstrated a significant reduction in resource use and costs for patients with substance abuse related medical conditions (Hilton et al 2003; Parthasarathy et al 2003).
Inpatient versus outpatient aftercare
9.23 A US study compared inpatient and outpatient provision for substance abuse patients (French et al 2000; McKay et al 2002). The groups were not randomised or matched. Inpatient care was demonstrated to yield higher net benefits, however inpatient care for drug abuse patients restricts opportunities for crime, which form a large component of the benefit. No separate results were presented for patients only dependent on alcohol.
QUALITY AND RELEVANCE OF THE EVIDENCE
9.24 The main problem with the evidence on psychosocial interventions is the lack of standardisation in the interventions. The effectiveness depends on what is delivered and how it is delivered and this needs to be reproducible if the same results are to be achieved.
9.25 As far as the economic studies are concerned, recent studies in this area relate to substance abuse treatment rather than alcohol treatment, which is increasingly common in the US literature (see for example Salome et al 2003). These studies tend to confirm the net benefits of treatment but cannot be directly transferred to the alcohol field because it is a feature of drug addiction treatment that the reduced costs of crime dominate the benefits. The economic outcomes based on HMO settings and other features of the US system also are not directly transferable to the UK.
MODELLING OF RESULTS FOR SCOTLAND
9.26 Slattery et al (2003) have modelled the cost-effectiveness of interventions in Scotland, building on the approach in Ludbrook et al (2002). All of the psychosocial interventions show net savings when future health care costs are offset against intervention costs. These savings range from £936 (BSCT) to £2252 (CSST) per additional abstinent patient but taking account of the 95% confidence intervals on effectiveness, there is no significant difference between the treatments. The additional use of pharmacological interventions produces additional savings of £822 per additional abstinent patient for Acamprosate and additional costs of £1521 for Naltrexone but again the 95% confidence intervals overlap. Data were not available to model the use of supervised Disulfiram but results for unsupervised Disulfiram show an additional cost of £4056 per additional abstinent patient, with the 95% confidence intervals overlapping those of Acamprosate and Naltrexone. All figures are in May 2002 prices.
9.27 The previous review (Ludbrook et al 2002) identified a need for further research in the areas of:
the separate and combined effects of naltrexone and acamprosate;
optimal treatment length;
better studies of the separate and combined effects of psychosocial and pharmacological interventions with clear description of the content of the psychosocial intervention;
developing economic models using clinical data from the UK for wider simulations;
using routine data from existing programmes to monitor existing treatments against research expectations.
Some studies have been identified in these areas but the research needs remain largely unmet.