Naltrexone for the management of opioid dependence

The term 'opioids' refers to opiates and other semi-synthetic and synthetic compounds with similar properties. Opiates are a group of psychoactive substances derived from the poppy plant that include opium, morphine and codeine. The term 'opiate' is also used for the semi-synthetic drug diamorphine (heroin), which is produced from poppy compounds. Opioid dependence can cause a wide range of health problems and is often associated with misuse of other drugs (including alcohol). Diamorphine is the most widely misused opiate, and its misuse can lead to accidental overdose. Injecting diamorphine may also be associated with the spread of blood-borne viruses, such as HIV and hepatitis B or C. The mortality risk of people dependent on illicit diamorphine is estimated to be around 12 times that of the general population. Psychiatric comorbidity – particularly anxiety, but also affective, antisocial and other personality disorders – is common among opioid-dependent people.

Associated social problems include marital and relationship breakdown, unemployment, homelessness, and child neglect, which often results in children being taken into the care system. There is also a clear association between illicit drug use and crime. Some opioid-dependent people become involved in crime to support their drug use. It is estimated that half of all recorded crime is drug related, with associated costs to the criminal justice system in the UK estimated at £1 billion per annum in 1996.

Biological, psychological, social and economic factors influence when and why a person starts taking illicit opioids. Use of opioids can quickly escalate to misuse (repeated use despite adverse consequences) and then dependence (opioid tolerance, withdrawal symptoms, compulsive drug-taking). The Diagnostic and statistical manual of mental disorders (4^th edition; DSM‑IV) defines dependence as 'a maladaptive pattern of substance use, leading to clinically significant impairment or distress'. Dependence syndrome has been defined in the 'International statistical classification of diseases and related health problems' (10th revision; ICD-10) as a 'cluster of behavioural, cognitive, and physiological phenomena that develop after repeated substance use and that typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state'. Physical and psychological dependence can develop within a relatively short period of continuous use (2 to 10 days), and is characterised by an overwhelming need to continue taking the drug in order to avoid withdrawal symptoms such as sweating, anxiety, muscle tremor, disturbed sleep, loss of appetite, and raised heart rate, respiratory rate and blood pressure. The body also becomes tolerant of the effects of opioids and the dose needs to be increased to maintain the effect. Getting the next dose can become an important part of each day and can take over a person's life. It is difficult to stop using these drugs and remain abstinent because the person experiences a combination of craving, unpleasant withdrawal symptoms, and the continuation or worsening of personal circumstances that led to opioid misuse in the first place.

When a person manages to remain abstinent, it may be after repeated cycles of cessation and relapse, with extensive treatment histories spanning decades. Nevertheless, some dependent people may make dramatic changes in their drug use without formal treatment. The histories of people using illicit diamorphine who attend treatment services suggest that most people develop dependence in their late teens and early twenties, several years after their first use of illicit opioids, and continue use over the next 10 to 20 years. Treatment can alter the natural history of opioid dependence, most commonly by prolonging periods of abstinence from illicit opioid misuse, allowing health and social circumstances to improve.

National estimates, which combine local prevalence data and routinely available indicator data, suggest that in the UK the prevalence of problem drug use is 9.35 per 1,000 of the population aged 15 to 64 years (360,811 people), and that 3.2 per 1,000 (123,498 people) inject drugs. The National Drug Treatment Monitoring System (NDTMS) estimates that in 2004 to 2005 there were 160,450 people in contact with drug treatment services in England. Most of the people in treatment were dependent on opioids. There are about 40,000 people in prison in England and Wales at any time who misuse illicit drugs. In 1 UK survey, 21% of prisoners had used illicit opioids at some point during their sentence, and 10% had used illicit opioids during the previous week.

The UK has a range of treatment services for opioid dependency. Pharmacological and psychosocial interventions are provided in the community and the criminal justice system, and include inpatient, residential, day-patient and outpatient services.

The interventions used for opioid-dependent people range from needle exchange to maintenance therapy and abstinence. Pharmacological treatments are broadly categorised as maintenance (also known as 'substitution' or 'harm-reduction' therapies), detoxification, or abstinence. The aims of the maintenance approach are to provide stability by reducing craving and preventing withdrawal, eliminating the hazards of injecting and freeing the person from preoccupation with obtaining illicit opioids, and to enhance overall function. To achieve this, a substitution opioid regimen (a fixed or flexible dose of methadone or buprenorphine to reduce and stop illicit use) is prescribed at a dose higher than that required merely to prevent withdrawal symptoms. The aim is for people who are dependent on illicit opioids to progress from maintenance to detoxification and then abstinence (when a person has stopped taking opioids). All detoxification programmes require relapse-prevention strategies and psychological support after detoxification because relapse rates are high. Some people can rapidly achieve total abstinence from opioids; others require the support of prescribed medication for longer than a few months. The opioid antagonist naltrexone can be used to help maintain abstinence.

Psychosocial and behavioural therapies play an important role in the treatment of drug misuse. They aim to give people the ability to resist drug misuse and cope with associated problems. For opioid-dependent people, these therapies are often an important adjunct to pharmacological treatments.

The government's Drug strategy (2004) aims to reduce the harm caused by illicit drugs by:

• increasing the number of people entering drug treatment programmes through the criminal justice system

• reducing the use of Class A and illicit drugs by people under the age of 25

• increasing enrolment in drug treatment programmes.

In England, naltrexone treatment accounts for 11,000 to 14,000 prescriptions per annum and a total annual drug cost of less than £500,000. The majority of naltrexone prescriptions are for opioid dependence, although naltrexone can also be used to treat alcohol dependence and other conditions.