Drug Abuse

Are detoxification programmes effective?
Richard P Mattick, Wayne Hall

The Lancet, January 13 1996; 347: 97-100
National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052, Australia
(R P Mattick PhD, Prof W Hall PhD)
Correspondence to: Prof Wayne Hall

Detoxification programmes provide supervised withdrawal from a drug of dependence so that the severity of withdrawal symptoms and serious medical complications are reduced to a minimum. Our main focus in this review is on the forms of supervised detoxification that are most common in the UK and other English speaking countries-namely, detoxification programmes for those dependent on alcohol and illicit opioids. We also briefly review detoxification procedures in other countries. Clinical procedures for detoxification or withdrawal from benzodiazepines, amphetamines, and other major drug groups are provided elsewhere.1

Detoxification programmes usually involve supervision in the period immediately after cessation of drug use, when the typical "rebound" symptoms of drug withdrawal are at their most severe. In "medicated" detoxification, the severity of withdrawal symptoms is minimised (or completely suppressed) by the administration of a drug that is not usually the drug of dependence.2 The agent selected is typically cross-tolerant to the drug of dependence and usually has a longer period of action (eg, benzodiazepines for alcohol and methadone for heroin). After the peak of the withdrawal syndrome, the substitute medication is gradually reduced. In "unmediated" or social detoxification, drug withdrawal is accomplished without pharmacological assistance, both in western countries and in Asian settings.3,4

Goals of detoxification

How we assess the effectiveness of detoxification programmes depends on what we believe their aims to be. If we regard detoxification as a treatment in its own right for alcohol or opioid dependence to achieve abstinence, then detoxification programmes are not especially effective. In our opinion, however, detoxification should not be regarded as a treatment for dependence per se, since prospective controlled studies show that people who have undergone detoxification are no less likely to relapse to drug use than those who, have not5-7 Many countries adopt services that seem to be based on the belief that detoxification can bring about lasting changes in drug use,' despite evidence to the contrary. Detoxification is more appropriately regarded as a process that aims to achieve a safe and humane withdrawal from a drug of dependence. This is a worthwhile aim in itself. Thus, the criteria for assessing its effectiveness are accordingly the rates of completion of the process, and the severity of withdrawal symptoms, distress, and medical complications.

Detoxification serves other purposes secondarily. In the case of severe alcohol dependence, it is a harm-reduction measure because timely supervised detoxification may prevent the emergency presentation of more serious and potentially life-threatening complications of heavy drinking such as delirium tremens: Since opioid withdrawal is rarely life-threatening, detoxification is a form of palliative care for those who wish to become abstinent or who have abstinence forced upon them (eg, as a result of imprisonment or admission to hospital).

Detoxification also provides a period of respite from drug use and its consequences, an occasion to reflect on the wisdom of continued drug use, and an opportunity to take up offers of intervention. Detoxification can thus be a prelude to more specific forms of drug-free treatment for drug dependence. The distress of withdrawal can be a barrier to achieving abstinence, and hence a drug user's fear of detoxification may be an impediment to entering treatment that aims to produce sustained abstinence.8

There are dangers, however, in forcing too close a connection between treatment and detoxification. First, the effectiveness of detoxification may come to be evaluated solely in terms of how many people are subsequently attracted into further treatment. Only a minority of drug-dependent people are likely to be attracted into even well-run detoxification programmes. Second, we should beware of imposing a requirement that a person shows serious interest in entering further treatment before being detoxified. Such a requirement is unlikely to improve the rate of recruitment into specific drug treatment,, it is more likely to select those who are skilled at simulating motivation for treatment rather than those who may benefit from detoxification. Third, detoxification is not a necessary prelude to treatment in the case of opioid dependence. The cross-tolerance and safety of oral methadone means that people who are dependent on illicit opioids can be transferred to maintained on oral methadone without any need or detoxification. When oral methadone is provided in adequate doses as part of well-run programmes that aim for long-term maintenance, illicit heroin use is substantially reduced, as are criminal activity, risks of contracting HIV and other infectious diseases, and deaths from overdose!

Panel 1:. Setting for and types of alcohol detoxification

Until a decade or so ago, standard alcohol detoxification was inpatient, fully medicalised treatment In a specialist drug and alcohol unit, usually with pharmacological management of withdrawal symptoms by decreasing doses of sedative drugs such as chlormethiazole or diazepam. The major change in the past decade has followed the realisation that a broader range of detoxification approaches can deal with the wide range of severity of withdrawal symptoms. Although residential specialist. detoxification continues to have a role, it need no longer be the method of first choice, although It unfortunately still remains so in many places.

Many people with mild to moderate withdrawal symptoms can be detoxified safety, successfully, and much more cheaply at -home under the supervision of a visiting nurse to administer anxiolytic drugs, with medical practitioners providing necessary medical support18,19 Even severely dependent drinkers may be detoxified safely and effectively at home with a minimum of medication and the support of a visiting nurse.20 Rates of completion for outpatient detoxification are sometimes, but not always,"" lower than residential detoxification programmes, probably because of greater availability of alcohol. Outpatient detoxification, however, is more acceptable to a wider range of dependent drinkers, many of whom are reluctant to be treated in a designated detoxification unit because of the attendant stigma21 Even when patients do not complete ambulatory detoxification, there is little. evidence of serious medical or psychiatric complications.22

Residential treatment seems necessary for the small proportion of dependent drinkers who are at risk of experiencing severe withdrawal symptoms (eg, those with a history of such symptoms, or a recent history of very high alcohol intake) and those who do not live in an environment that supports outpatient detoxification (eg, the homeless, or those living in boarding houses where there are other heavy drinker;). Residential detoxification need not, however, be pharmacologically assisted or medically supervised. Clinical experience in' non-medical' detoxification units in Canada and Australia shows that in many cases withdrawal symptoms can be safely and successfully managed without medication in a quiet, safe, supportive environment, with counselling, reassurance, and social support from non-medical staff to manage withdrawal symptoms. For safety reasons, such facilities usually have ready access to medical assistance in the event of one of the rare life-threatening complications of alcohol withdrawal, though transfers to specialist medical care are hardly ever necessary. In one Australian series of over 4000 patients, for example, less than 0•596. of cases required hospital care for acute alcohol withdrawal." Deaths during alcohol withdrawal are now very rare24

Inpatient medically assisted detoxification is needed by those at greatest risk of life-threatening delirium tremens or seizures: those with a previous history of either symptom, those with severe symptoms on the current presentation, or those with concurrent medical or psychiatric disorders that may complicate their management. The preferred agents for minimising withdrawal symptoms are long-acting benzodiazeplnes, either alone or with other medications such as clonidine and betablockers.12,25 Suitable regimens are well described elsewhere" It is generally recommended that all moderately to severely dependent drinkers who are undergoing withdrawal (including those in 'non-medical' detoxification programmes) should also be given doses of thiamine as prophylaxis against Wemicke's encephalopathy.

Alcohol detoxification

Alcohol withdrawal syndrome

The signs and symptoms of the alcohol withdrawal syndrome can develop in dependent drinkers within 6-24 h of their last drink. Although the syndrome is often presented as a neatly and clearly defined set, there are some difficulties in attributing many of the non-specific symptoms unequivocally to the alcohol withdrawal syndrome, either as a physiological effect or as an affective response to withdrawal 9, There has been surprisingly little systematic research on the nature of the syndrome,10,11 so most descriptions continue to be based on clinical wisdom.2

Three subsets of signs and symptoms on a continuum of increasing severity and seriousness are often 1 autonomic nervous system hyperactivity, neuronal excitation, and delirium tremens. Their pathophysiology is discussed elsewhere.12,15,16 The first symptoms occur within hours of the last drink, usually peaking within 2448 h, and include restlessness, sweating, tachycardia, systolic hypertension, tremors, nausea, vomiting, and anxiety. More serious symptoms are epileptiform seizures (usually grand mal), which occur very rarely: onset is within 24 h of cessation, with very few seizures evolving into status epilepticus.17 In delerium tremens, the most severe subset, there is a pronounced loss of insight, severe distortion of perception, sensation, and arousal (including auditory and visual hallucinations), and severe disorientation, confusion clouded consciousness, impaired attention, and disturbed sleep. Hyperthermia is common and death may occur from cardiovascular collapse.' Although up to 20% of such patients have died in previous series, for well managed patients the death rate from withdrawal is likely to be much lower at 5% or less." In most patients, the symptoms of alcohol withdrawal are mild to moderate, without serious medical consequences; they are self limited in that they disappear within 5-7 days after the last drink. In more severe cases, which account for perhaps less than 5% of cases, delirium tremens may develop.

Unresolved Issues

Research on detoxification over the past few decades has produced a more benign view of the alcohol withdrawal syndrome than the view that arose from experience in

specialist medical settings, where only the most severe complications of alcohol withdrawal were seen. Coincidentally, developing conceptions of alcohol dependence have raised a question about the importance of the experience of withdrawal symptoms.'

A major consequence of this more benign view of the alcohol withdrawal syndrome has been a proliferation of different types of, and settings of, detoxification for people with differing severity of alcohol withdrawal symptoms (see panel 1 below). An issue raised by this proliferation is how we decide which individuals are most suitable for which forms of detoxification. Although there are clinical guidelines for making such decisions,26 they are currently open to wide interpretation and judgment. The careful development of appropriately sensitive and specific screening methods, together with simple protocols relating to patient responses, as judged by symptom-rating scales, to management methods may lessen the inaccuracy of these judgments.

Research on treatment provision is needed to ensure that these general improvements in the delivery of detoxification do not inadvertently lead to an oversupply of detoxification services. There is the possibility, for example, that the development of home/ambulatory detoxification programmes may attract into formal detoxification programmes alcohol-dependent people who do not need supervision. This could have the undesirable consequences of increasing rather than reducing overall detoxification costs, and inadvertently encouraging some dependent drinkers into a role of chronic dependence and reliance on detoxification services.27

Panel 2: Setting for opioid detoxification

There is more reason for choosing inpatient rather than outpatient detoxification for opioid dependence. Several investigators have found inpatient detoxification to be superior to outpatient detoxification in terms of the proportion of patients who complete the process; In one study," rates of 81% and 17%, respectively, were achieved. However, others have reviewed retention rates in studies of inpatient and outpatient detoxification and concluded that the completion rates differ substantially, clearly favouring inpatient programmes , 3 3 with outpatient retention rates of about 20% and inpatient rates between 50% and 77%. It may be the case that opioid-dependent people are more likely than alcohol-dependent people to live in errAronments (eg, with other opioid users) that are unsupportive of detoxification and abstinence, and hence are less likely to complete outpatient detoxification. The interpretation of these studies is complicated by the fact that the intensity of Intervention and support have typically been greater in the Inpatient than in the outpatient setting.

Recently there have been clinical reports of rapid opioid detoxification being achieved within 48 h by use of general anaesthesia and opioid antagonists. This seems an expensive way of providing a palliative treatment, and one moreover that adds a small risk of death in a condition that is not life-threatening.

 

Opioid detoxification

Opioid withdrawal syndrome . The opioid withdrawal syndrome is characterised by various signs and symptoms, including eye-watering, runny nose, yawning, and sweating, which occur 8-12 h after the last dose of heroin or morphine, followed by increasing restlessness, dilated pupils, piloerection, tremor, irritability, anorexia, bone and joint pain, and stomach cramps. As symptoms peak at 48-72 h, the dependent user will experience an intensification of symptoms: insomnia, more pronounced lack of appetite, violent yawning and sneezing, severe eye-watering, profuse nasal discharge, and inflammation of the nasal mucous membranes. The symptoms largely disappear within 7-10 days, although this does not imply that there is a restoration of physiological equilibrium associated with opioid dependence' There seems to be a longer term secondary or protracted abstinence syndrome consisting of general malaise, fatigue, decreased wellbeing, poor tolerance of stress, and a craving for opioids, which may last some months, when there is a high rate of relapse to regular opioid use. The extent to which this secondary syndrome is in fact a result of drug withdrawal, rather than the user experiencing a normal state, is unclear, and controlled studies of the occurrence of withdrawal symptoms are needed.

Unlike the the alcohol withdrawal syndrome, the opioid withdrawal syndrome is very rarely life-threatening. It has been described as "immiserating" and like having an episode of bad influenza that lasts about a week."" Nonetheless, the syndrome is sufficiently aversive for many opioid-dependent people for it to be an obstacle to abstinence; the drug needs to be removed humanely and effectively for those who wish to cease all opioid use.

Types and settings for opioid detoxification

Many factors influence rates of completion of opioid detoxification. These include the person's reasons for undertaking detoxification, and the choice of methods available to assist. The reasons why opioid-dependent people want detoxification may be mixed: they may be acting under coercion because of criminal charges; they may be stabilised methadone patients who choose to withdraw from methadone maintenance; they may intend to reduce the dose of opioid they require so that they can use illicit drugs at a lower and more affordable dose; or they may be dependent on illicit opioids and wish to become abstinent.

The effectiveness of different opioid withdrawal regimens has been well researched and reviewed in detail."' Since World War II, the method of choice has become methadone-assisted withdrawal provided on an inpatient basis. (The setting for opioid=.detoxification is discussed in panel 2.) Milby reviewed 50 studies of detoxification from heroin using methadone conducted between 1970 and 1986. He found that rates of withdrawal symptoms had decreased whereas rates of completion of detoxification had increased over the three 5 -year periods examined (40% to 55% to 75%), reaching as high as 80% completion in the later studies. The gradual improvement in outcome was associated with the increased use of medications to ameliorate withdrawal symptoms and/or shorten the withdrawal period. These medications were methadone, Condine alone, or Condine with naltrexone/naloxone."•" The changes in completion rates suggest that methadone-assisted withdrawal is an effective method of achieving opioid withdrawal over a period of a week to 10 days, especially when compared with the rates of successful completion of self-detoxification attempts (24%) reported for opioid dependent patients."

The alpha-adrenergic agonist Condine has challenged the dominance of methadone. There is now a reasonable amount of research comparing the safety and efficacy of methadone-assisted and Conidine-assisted opioid withdrawal, and this has been comprehensively reviewed." Methadone-assisted withdrawal has been marginally better than Condine-assisted withdrawal in terms of rates of completion and the experience of withdrawal symptoms."" The two drugs seem to differ, however, in the timing and the profile of withdrawal symptoms. Patients receiving clonidine report more serious withdrawal symptoms early in detoxification when they are most likely to drop out, whereas with methadone patients have fewer symptoms early in the process but report more symptoms as the last doses of the drug are withdrawn. Patients who experience the most severe withdrawal symptoms are not well controlled by Conidine, so are more likely to drop out, whereas those with mild-to-moderate symptoms have fewer problems with clonidine and are more likely to complete detoxification. Clonidine also has some potentially serious side-effects, which include hypotension, sedation, insomnia (especially during first few days of detoxification), and psychotic symptoms in those who are vulnerable because of psychiatric disorder. Clonidine seems to be a less useful drug than methadone for opioid detoxification, although more discriminating use of clonidine may enable a substantial group of opioid dependent patients to complete detoxification successfully.

The emphasis on pharmacological approaches to opioid detoxification has led to a neglect of the psychosocial methods that have been successful with alcohol detoxification. There is limited evidence for the effectiveness of other approaches to opioid withdrawal. Giving clients clear information about the course of opioid withdrawal is important, and has been associated with significantly increased completion rates and decreased subjective withdrawal distress.„ Other methods of opioid detoxification have had their proponents, although their efficacy remains to be demonstrated. Among these methods have been cranial electro stimulation, which has proved inferior to methadone-assisted withdrawal in two controlled studies, although two other investigations showed promising results.In Thailand, a 10-day non-pharmacologically assisted detoxification involving induced vomiting and steam-baths to purge the patient has been adopted, although the 6-month abstinence rate is 20-30%!'

Future directions

Recently, partial or complete opioid antagonists have shown potential for managing opioid detoxification. Buprenorphine, a mixed opioid agonist-antagonist produces no withdrawal signs in heroin-dependent patients who transfer to it, although mild-to-moderate symptoms have been reported!' More research is needed to firmly establish its efficacy compared with other opioid agonists as a withdrawal agent, but it seems to be equivalent in effect to methadone for heroin detoxification" and to be superior to clonidine and other drugs." Of particular interest is the suggestion that it has a potential to reset the endogenous opioid system towards normal baseline functioning, an effect that is thought less likely' to occur with a pure agonist such as methadone41. A further topic that requires more research is the role of pure antagonists (eg, naltrexone) to assist in detoxification."

We acknowledge the helpful comments of Ms Dorothy Oliphant, Mr Erol Digiusto, and Dr Jason White on drafts of this paper

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