The clinical goal-oriented approach requires clarity about the clinical objectives at each phase of the treatment process. A typical treatment plan involves three primary clinical objectives:

Stabilization with a substitution treatment (e.g. methadone or buprenorphine in opiate addiction) involves prescribing a pharmacological equivalent to the abused drug to stop illicit use, crime, etc. It allows time for stabilization to occur and to consider later objectives. Stabilization itself may be either short-term with the primary goal of terminating illicit drug use ‘on top’ of the prescription, or longer-term where it is commonly known as maintenance. The goals of maintenance are either psychosocial stabilization in preparation for detoxification, or harm reduction in patients where abstinence is not practicable or safe. Unless a sufficient degree of stabilization has been achieved prior to detoxification, the chances of success are strictly limited. The harm-reduction goal has generated much controversy, but one of its major benefits is the reduction in the spread of HIV among injecting drug users. In this group stable long-term maintenance treatment is preferable to repeated cycles of premature discontinuation followed by relapse to uncontrolled drug use with its attendant elevated risk of death from overdose as tolerance wanes. Monitoring by using drug screens and clinical assessments is required to ensure that patients do not use ‘on top’ of their prescription.

This chapter deals with methadone, levacetylmethadol (LAAM), codeine and dihydrocodeine tartrate, buprenorphine, clonidine, lofexidine, naltrexone, naloxone, acamprosate, disulfiram, and clomethiazole (chlormethiazole), and covers addiction indications only. Many of these drugs are not licensed for use in addiction treatment (e.g. methadone tablets and injection), or are currently licensed in only one or a few countries (e.g. clonidine in Germany, lofexidine in the United Kingdom).

This is a long-acting opioid analgesic which has been the mainstay of opioid substitution treatment, but is often difficult to stop due to its prolonged withdrawal syndrome.

Pharmacology: it is a strong full µ-opioid agonist.

Types of compounds available: it is available in liquid, injectable, and tablet formulations.

Pharmacokinetics: t_max 2 to 4 h after oral dosing; 1 h after intramuscular injection; its half-life is 25 h.

Side-effects: as with other µ-opioids, its side-effects include mental blunting, sweating, constipation, nausea, and analgesia.

Toxic effects: acute overdose leads to respiratory depression and pulmonary oedema.

Indications: opiate maintenance, stabilization, and detoxification; it is also indicated for use during pregnancy.

Contraindications: respiratory or severe liver disease, monoamine oxidase inhibitors; caution should be exercised in elderly people.

Interactions: respiratory depression especially in combination with other sedative drugs; metabolism affected by hepatic enzyme induction and inhibition; plasma levels are affected by HAART drugs.

Effects of withdrawal: these include moderate but prolonged abstinence syndrome, especially poor sleep.

Dosage and administration: single daily dose, occasionally twice daily; dose depends on the level of dependence—if unknown, initially 10 to 20 mg daily. The minimum dose that covers withdrawal symptoms for 24 h should be given, and increased by 5 to 10 mg as necessary. Close monitoring is necessary by clinical assessment and drug screen. Some centres use intravenous preparations in those who don’t respond to oral preparations.

LAAM is a methadone variant with a much longer half-life, requiring only three visits a week for full supervision of medication. However, take-home medication is not allowed and its use is restricted to specialist clinics and is reserved for patients who have failed other treatments. Its licence in Europe has been withdrawn due to QTc prolongation.

Pharmacology: it is a synthetic µ-opioid agonist with active metabolites which are more potent than the parent drug.

Types of compounds available: aqueous solution.

Pharmacokinetics: t_max 2 to 4 h; duration of action is 48 to 72 h; half-lives for LAAM and its metabolites are 2 to 4 days; it takes 2 weeks to reach steady state.

Side-effects: too rapid escalation of the dose may result in sedation, orthostatic hypotension, poor concentration, and overdose.

Toxic effects: as for methadone; QTc prolongation; overdose occurs with too frequent (daily) dosing, use of multiple drugs, or ‘on-top’ use due to impatience with its slow onset of action.

Indications: opiate maintenance, stabilization, and detoxification.

Contraindications: pregnancy (transfer to methadone); QTc prolongation prior to induction of treatment; dose should be reduced in elderly people, and in renal and hepatic impairment.

Interactions: as for methadone; other drugs prolonging QTc interval.

Effects of withdrawal: as for methadone, but with a milder withdrawal syndrome due to longer t_1/2.

Dosage and administration: pre-treatment ECG to identify prolonged QTc intervals, repeated 12–14 days after initiating treatment and periodically thereafter to rule out alterations to the QTc; give three times a week or on alternate days; increase dose by 20 to 40 per cent when transferring form 48 h to 72 h dosing interval. Transfer methadone to LAAM by giving 1.2 to 1.3 times the daily methadone dose; and LAAM to methadone by waiting at least 48 h and then giving 0.8 times the LAAM dose. If low or unknown tolerance, the initial dose is 20 to 40 mg three times weekly. Adjust dose in 5- to 10-mg steps, but no more frequently than
weekly at the most. Strongly warn patients of the risk of supplementation with street drugs especially prior to steady state. LAAM is detected by urine screens for methadone.

Advantages over methadone and other full µ-agonists are its safety in overdose, the attenuation of the drug ‘high’ during on-top use, and its low levels of psychological reinforcement and withdrawal symptomatology during detoxification.

Pharmacology: a partial µ-opioid agonist, which explains the ceiling on respiratory depression; slow onset of action; dissociates slowly from the µ-receptor.

Types of compounds available: 0.2-, 0.4-, 2- or 8-mg sublingual tablets, or 0.3-mg ampoules for injection; it is also available in combination with naloxone in a 1:4 ratio (Suboxone®) to reduce misuse if diverted.

Pharmacokinetics: sublingual tablets absorbed rapidly into the buccal mucosa and released slowly into the blood stream; t_max 2 to 6 h.

Side-effects: withdrawal symptoms if either too little or too much is given; nausea and vomiting are rare in addicts.

Toxic effects: as for methadone, but less constipation and respiratory depression.

Indications: opiate maintenance, stabilization, and detoxification, including in pregnancy; may be especially suitable for opioid antagonist-assisted withdrawal; no dosage adjustment needed in renal failure or elderly people.

Contraindications: severe respiratory disease; use with care in severe liver disease.

Interactions: rare; sedation with benzodiazepines.

Effects of withdrawal: there is a mild but delayed withdrawal syndrome.

Dosage and administration: initial dose is 0.8–4 mg increasing by 4 to 8 mg daily until the required dose level is reached; usual daily dose 8 to 32 mg; doses above 12 mg maybe given on alternate days; minimize withdrawal symptoms after long-term use by reducing by 1 mg every 3 to 4 days or less often; buprenorphineassisted heroin detoxification by rapid reduction over 5 to 10 days; the injectable form is not recommended for use in addiction treatment. Monitor clinical state and perform drug screens for compliance and on-top use.

Advantages over methadone occur in situations where long-acting opioids may be inappropriate. These are often preferred by patients, and by doctors treating the young, low-dose users, and in acute situations (e.g. in police custody). Disadvantages are its ease of misuse, high levels of psychological reinforcement due to its rapid onset of action, and its unfavourable side-effect profile.

Pharmacology: it is a weak short-acting µ-opioid agonist.

Types of compounds available: Codeine: 15-, 30- and 60-mg oral tablets, linctus, syrup and injection; dihydrocodeine tartrate: 30- or 40-mg oral tablets for use three to six times a day, and a 60-, 90-, or 120-mg slow-release preparation (DHC Continus) for use every 12 h; also parenteral preparation and elixir.

Pharmacokinetics: peak plasma levels at 1 to 2 h; half-life 3.5 to 4.5 h.

Side-effects: it is more likely to cause sedation, dizziness, stimulation, euphoria, constipation, histamine release, psychomimetic effects, and disturbing dreams than other opioids.

Toxic effects: precipitation of life-threatening exacerbations of asthma; in overdose, coma with myotonic twitching, grand mal convulsions, and rarely rhabdomyolysis may occur.

Indications: opiate maintenance, stabilization, and detoxification

Contraindications: acute exacerbations of asthma, lower respiratory tract infection, respiratory depression, and hepatic failure, increased intracranial pressure; caution should be exercised in renal impairment and elderly people.