Methadone maintenance

Maintenance treatment involves the prolonged prescription of a drug with no intention to reduce the dose, whereas detoxification is any treatment intended to produce abstinence from drug use (including prescribed drugs).

Methadone is a long-acting opioid agonist that is used to prevent withdrawal symptoms in opioid addicts. Persistent use leads to cross-tolerance and reduces the reinforcement effects of illicit opiates. Ward et al(1999) have produced an excellent short review of methadone treatment.

An influential meeting of experts in the USA concluded that the safety and efficacy of methadone maintenance treatment ‘has been unequivocally established’ (National Consensus Development Panel, 1998). Many studies have shown the advantages of methadone maintenance in reducing drug use, criminality and blood-borne virus infection and improving general health and social status. The median death rate for addicted individuals maintained on methadone is 30% of that for those who are not in treatment. Urine analysis from one sample of 435 methadone maintenance clients showed that almost half were able to quit daily heroin after 12 months (Reference Simpson, Joe and Rowan-SzalSimpson et al, 1997). The average number of ‘crime-days’ fell from eleven per month to four. Two large cohort studies suggest that the odds of HIV infection were five times greater among those who were not in methadone maintenance treatment than among those who were (Reference Ward, Hall and MattickWard et al, 1999).

A classic double-blind study involved 100 heroin addicts in Hong Kong who were randomised to methadone maintenance or methadone detoxification at 1 mg/day (Reference Newman and WhitehillNewman & Whitehill, 1979). Retention rates were 60% in the maintenance group and 5% in the detoxification group. Urine analysis at 2-year follow-up indicated that 70% of subjects in the maintenance group had abstained from illicit opiate use in the previous month.

Methadone doses above 60 mg per day are often required to prevent heroin use. However, it is important to note that initial methadone doses should be less than 40 mg per day to prevent accidental overdose in individuals who have not developed a high tolerance to opiates. One study concluded that patients who receive doses of less than 60 mg of methadone have nearly five times the risk of dropping out as those who receive doses of 80 mg or more (Reference Capelhorn and BellCapelhorn & Bell, 1991). A double-blind trial of 193 intravenous opiate addicts revealed that 53% of the urine samples after 30 weeks were heroin-positive in those randomised to 80–100 mg methadone, compared with 62% of those on 40–50 mg (Reference Strain, Bigelow and LiebsonStrain et al, 1999).

Contingency management in methadone maintenance and cocaine treatment

Contingency management techniques make clinic privileges or even continued prescribing available pending objective evidence of abstinence from illicit drugs.

McCarthy & Borders (1985) reported a controlled trial of 69 patients on methadone maintenance programmes who were randomised so that for half the patients, prescribing would be discontinued after 4 consecutive months with one or more opioid-positive urine result. Intention-to-treat analysis indicated that 48% of patients in the trial sample were drug-free at one year compared with 31% in the more liberal control group. Unfortunately, aversive control techniques (such as reduction of methadone) lead to some patients leaving treatment. Positive control techniques are reported by Stitzer et al(1992) in a study of 53 patients in methadone maintenance who were randomly assigned to contingent or non-contingent take-home privileges: up to three take-home doses per week were permitted following 2 consecutive weeks of drug-free urine samples. The contingent group produced more individuals with at least 4 consecutive weeks of abstinence (32% v. 8%) over the 6-month trial.

Comparable results are reported in a randomised controlled trial of opiate and cocaine addicts in which clean urine samples were rewarded with vouchers that could be exchanged for retail goods (Reference Higgins, Budney and BickelHiggins et al, 1994; Reference Preston, Umbricht and EpsteinPreston et al, 2000).

Other agents used in the treatment of opioid dependence

Clonidine and lofexidine are α₂-adrenoreceptor agonists that reduce somatic symptoms of opioid withdrawal. Opioid detoxification with these agents can be achieved in 5–7 days. However, neither agent can suppress symptoms such as craving, lethargy, insomnia, restlessness and muscle aches. Adverse effects include sedation and hypotension, although these are less common with lofexidine.

A systematic Cochrane review of 10 studies comparing α₂-agonists and methadone detoxification over 10 days found no difference in efficacy, although more clients remained in contact with treatment services following methadone detoxification (Reference Gowing, Farrell and AliGowing et al, 2002). Kleber et al(1985) reported a trial of 49 methadone maintenance patients randomised to out-patient detoxification with clonidine or reducing doses of methadone over 30 days. Forty per cent completed the detoxification process, of whom one-third were abstinent at 6-month follow-up. An equivalent proportion had returned to methadone maintenance. There was no significant difference in outcome between the groups.

Buprenorphine is a partial opioid agonist and partial antagonist that is given sublingually. It might have a lower risk of overdose than methadone and produce less severe dependence, allowing a smoother withdrawal than methadone. A meta-analysis identified five randomised clinical trials, involving 540 patients over 16–26 weeks. This showed that buprenorphine was comparable with methadone in preventing illicit drug use, although it was more expensive (Reference Barnett, Rodgers and BlochBarnett et al, 2001). Around 50% of urine tests were positive for illicit opiates. Doses of 8–12 mg per day of buprenorphine have been shown to be as effective as 60–90 mg of methadone (Reference Schottenfeld, Pakes and OlivetoSchottenfeld et al, 1997). The risk that oral buprenorphine will be injected is greater than that for oral methadone and to deter this, a combination of buprenorphine with naloxone is being developed (the naloxone nullifies the buprenorphine only when injected).

Naltrexone is an opioid antagonist that produces no psychoactive effects or dependence. Naltrexone completely blocks the effects of opiates and acts as an ‘insurance policy’ against opiate use. It can precipitate acute withdrawal and should only be used following abstinence from all opioids (including methadone). Treatment can be given daily or three times per week. Unfortunately, naltrexone has not proven effective in treatment settings (Reference Kirchmayer, Davloi and VesterKirchmayer et al, 2002), although peculiarly, some investigators appear to have viewed it as a direct alternative to methadone rather than as an approach that can enable a completely opiate-free state. For example, in one trial only 15 of 300 patients chose naltrexone instead of detoxification or methadone maintenance, and of those 15, only three continued naltrexone for more than 2 months (Reference Fram, Marmo and HoldenFram et al, 1989).

L-alpha-acetylmethadol (LAAM) is a long-acting opiate agonist like methadone. It is not available in the UK, following reports of cardiotoxicity.

Ultra-rapid opiate detoxification

Ultra-rapid opiate detoxification involves administration of opiate antagonists (naloxone and naltrexone) to opiate-addicted individuals under general anaesthesia. This leads to an acute withdrawal. No large-scale controlled trials of this procedure have been published (Reference O'Connor and KostenO'Connor & Kosten, 1998). Concerns about safety, expense and effectiveness also limit its usefulness. Ultra-rapid opiate detoxification was recently the subject of a General Medical Council investigation following the death of a patient during recovery, resulting in the anaesthetist involved being struck off (Reference BedenochBedenoch, 2002). It seems unlikely that there will be any enthusiasm for ultra-rapid opiate detoxification among clinicians in the foreseeable future, although less drastic measures involving sedation rather than anaesthesia are not so controversial.

Injectable opioid treatment

Heroin is available to addicts in the UK from licensed specialists. Parenteral methadone is also available, with licensing not required. Hartnoll et al(1980) reported a 12-month follow-up trial of intravenous heroin v. oral methadone on 96 heroin-addicted individuals in London. Those on heroin maintenance were twice as likely to remain in treatment (74% v. 29%). However, the proportion remaining dependent on opiates (prescribed and illicit) at 12 months was higher in the heroin maintenance group (90% v. 70%). There were no differences between the groups for self-reported criminal activity, health or employment. This report led to greatly reduced enthusiasm for injectable opioid treatment. Another UK trial found no advantage between injectable methadone and oral methadone (Reference Strang, Marsden and CumminsStrang et al, 2000).

Injectable opioid treatment is claimed by some enthusiasts to engage users in treatment more effectively than oral alternatives. Opponents suggest that it perpetuates injecting behaviour and thereby postpones eventual abstinence from heroin and also, in effect, endorses injecting. The treatment is expensive and there is a risk of deep-vein thrombosis and infection. The prospect of being offered injectable opiates may also provide some users with a vested interest in poor compliance with methadone maintenance. Relatively few patients are ever likely to receive the treatment, so the overall effects on crime will be small. Needle exchange programmes probably reduce health risks more than the prescription of injectables. The available evidence does not support the widespread adoption of injectable opioid treatment.

Intensity of psychotherapy

Many studies have shown that the intensity and duration of involvement in drug misuse treatment programmes is one of the best predictors of outcome (National Consensus Development Panel, 1998). However, the ‘more is better’ idea is often based on uncontrolled follow-up studies, in which patient motivation and selection might be primarily responsible for the good outcome.

Kraft et al(1997) reported a trial of 100 opiate-addicted patients, randomised to three psychosocial treatments of 6 months duration: minimum-contact methadone maintenance; methadone maintenance plus standard drug counselling three times weekly; and an enhanced programme of psychosocial treatment with daily counselling, family therapy and social work activity to enhance job prospects, housing and address other social problems. However, many of the subjects who were randomised to the enhanced programme actually attended only once each week, despite the offer of more-frequent sessions. All patients received 60–90 mg methadone per day. Abstinence from opiates and cocaine use at 1 year were 29%, 47% and 49% of clients in the minimum-contact, standard and enhanced groups, respectively. These results were less promising than a partially randomised earlier trial. Overall, the enhanced programme did not confer significant benefit over standard drug counselling, although it was better than minimum-contact methadone maintenance. A cost-effectiveness analysis confirmed this.

Narcotics Anonymous and its 12-step approach

Narcotics Anonymous provides support groups for problem drug users. These groups are widely available and are free to participants. Applying the disease model to substance misuse, they promote the 12-step approach. This involves recognition that addiction is a relapsing illness that requires complete abstinence (Box 2). Participants are required to acknowledge their addiction and the harm they are causing themselves and others. No randomised controlled trials have attempted to determine the effectiveness of Narcotics Anonymous or of 12-step approaches in opiate addiction. However, a study of 487 cocaine users, all of whom received group drug counselling throughout the trial, involved randomisation to individual counselling (based on the 12-step approach), supportive–expressive psychotherapy or cognitive–behavioural therapy (CBT) with a 1-year follow-up (Reference Crits-Christoph, Siquel and BlaineCrits-Christoph et al, 1999). One-third of the eligible cocaine users were recruited, of whom 28% completed the 6-month treatment programmes. Cocaine use was reduced from a mean of 10 days per month to only 3 days. However, 71% of the group receiving a combination of individual and group 12-step counselling were abstinent for at least 1 month, compared with 55–60% for combinations of group counselling with formal psychotherapy. The psychotherapy approaches were able to retain more clients in treatment (33% completed treatment v. 22% for drug counselling). Similarly, Wells et al(1994) report a controlled comparison of CBT-based relapse prevention v. 12-step approaches in out-patient treatment of 110 cocaine users. The two treatments were equally effective at 1 year, and the number of days of cocaine use halved. Overall, the evidence suggests that the 12-step approach is at least as effective as other structured psychotherapies.

Relapse prevention and cognitive–behavioural therapy

Relapse prevention techni ques using CBT are based on the work of Marlatt & Gordon (1985). The techniques assume that substance misuse is a means of coping with difficult situations, dysphoric mood and peer pressure. Treatment aims to help patients recognise high-risk situations and either avoid or cope with them without drug use.

Irvin et al(1999) reported a meta-analysis of five randomised controlled trials of relapse prevention treatment for polydrug misuse. The overall effect was modest. For example, Carroll et al(1994) compared CBT-based treatment with routine clinical management over 1 year for cocaine addicts. CBT was only superior for those who were also depressed and for those with high levels of cocaine use. Wells et al(1994) found no difference between CBT-based relapse prevention and a 12-step approach in cocaine users (see above).

In one randomised controlled trial with 64 amphetamine-using patients, 2–4 CBT/motivational interviewing sessions were compared with provision of a self-help booklet. Clients typically attended half the sessions. The number of clients who abstained from amphetamine use in the treatment group compared with the self-help group increased from 21% to 38% (Reference Baker, Boggs and LewinBaker et al, 2001).

Overall, CBT approaches are better researched, but probably no more effective than the other psychological methods in addiction.

Psychodynamic psychotherapy

There is a widespread opinion that psychodynamic psychotherapy is of low acceptability to drug misusers, as illustrated by a trial of interpersonal psychodynamic psychotherapy with 72 opiate addicts in methadone maintenance (Reference Rounsaville, Glazer and WilberRounsaville et al, 1983). Weekly individual interpersonal therapy was compared with monthly ‘low-contact’ control treatment. Both treatments continued for 6 months. Only 5% of eligible clients agreed to attend psychotherapy and only 38% of these completed the interpersonal therapy programme. There were no significant differences in outcome between the two groups, although both made significant gains. Woody et al(1995) reported a similar randomised trial of supportive–expressive psychotherapy, in which the overall effect size was small (0.26). Other investigators have failed to find advantages for psychodynamic psychotherapy in substance misuse (Reference Crits-Christoph, Siquel and BlaineCrits-Christoph et al, 1999).

Motivational interviewing/motivational enhancement therapy

Motivational interviewing is a technique described by Miller & Rollnick (2002). It is based on theories of cognitive dissonance and attempts to promote a favourable attitude change. Briefly, instructing addicts of the problems of dependency and the advantages of abstinence tends to provoke contradictory arguments from the client. This might reinforce continued dependence. Motivational interviewing encourages clients to give their own reasons for attempting to change their drug use.

A systematic review identified five randomised trials of motivational interviewing in drug dependence, involving 800 patients (Reference Dunn, Deroo and RivaraDunn et al, 2001). Typical effect sizes were 0.5–0.6 (although confidence intervals were large). One randomised trial of 122 opiate addicts found that motivational interviewing compared with health education alone increased retention in methadone programmes at 6 months from 50% to 70% (Reference Saunders, Wilkinson and PhillipsSaunders et al, 1995). Booth et al(1998) reported a trial of 4000 intravenous drug users seeking HIV testing. Subjects were randomly assigned to either standard testing alone or testing plus three sessions of motivational counselling from a health educator. At 6-month follow-up, the latter group showed half the rate of drug injection (20% v. 45%) and were four times more likely to be abstinent (confirmed by urine analysis). They also had significantly lower arrest rates (14% v. 24%).

Community reinforcement, couple and family therapies

Reinforcement treatments typically involve clients’ partners or families rewarding them for abstinence using agreed strategies. Stanton & Shadish (1997) performed a meta-analysis of 15 randomised controlled trials, involving 1571 opiate addicts, that compared couple/family therapy with individual counselling, peer-group therapy and family psychoeducation. Six of the trials involved adult clients. Family therapy methods had an effect size of 0.46 greater than non-family therapy at 1 year. The drop-out rate was also lower in the family therapy group (∼45% compared with ∼25%).

Community reinforcement using families and couples are feasible and show some effectiveness, although they are often overlooked. Not all clients have family members or partners who are willing to be involved in substance misuse treatment. However, where they can be recruited as co-therapists, family members can be encouraged to provide agreed rewards to clients for abstinence. The nature of the reward needs to be negotiated in advance with the client and family member. Family members also provide a degree of surveillance over the clients and can provide supervision, support, advice or comment if clients begin using drugs again, feel tempted or put themselves in risk situations.

Therapeutic communities and residential rehabilitation units

These units typically require prolonged residence (often 12–18 months). Clients are closely involved in running the programmes, including selecting and discharging residents. Abstinence is usually a pre-requisite. Several large studies suggest that therapeutic communities are beneficial, although completion rates for prolonged residential programmes are often below 20%.

A trial of 585 male heroin addicts involved random assignment to methadone maintenance or therapeutic communities (Reference Bale, Stone and KuldauBale et al, 1980). The outcomes between the two groups were comparable. Roughly half of the subjects who completed the programmes reported heroin use during the 12th (and final) month of the study. Unfortunately, only 18% of the subjects randomised to the therapeutic communities actually began the 6-month residential programmes. Overall, only 10% of subjects successfully engaged in either of the programmes to which they had been assigned.

The National Treatment Outcome Research study is a follow-up of 1075 clients (most of whom were addicted to heroin) attending UK drug treatment agencies (Reference Gossop, Marsden and StewartGossop et al, 2003). At 5 years, 42% of those who were attending community methadone programmes at the start of the study were regularly using heroin, compared with 39% of those who were in residential programmes at intake (and were subsequently discharged). Although the study was not randomised, these results support North American research demonstrating that residential programmes are no more effective than community programmes, despite the greatly increased cost.