Opioid. Withdrawal from dependence30 is usually managed by substituting another opioid drug. Methadone is the treatment of choice; it has an affinity for the p receptor that is similar to that of morphine but occupies it for longer (24 h) and its slow offset of effect attenuates withdrawal symptoms. Upward titration of its effect to the dose that prevents withdrawal symptoms is relatively straightforward (initial dose 10-20 mg/day). Thereafter serial reductions in dose are made; in the most rapid regimen this takes 7-21 days but more commonly the process takes many months with more gradual decrements as the dose is lowered. Methadone is also the preferred drug in opioid maintenance programmes for addicts who decline to withdraw.
Methadone is less likely to be diverted (traded on the black market) than shorter-acting drugs. In the UK a special Methadone Mixture 1 mg/ml (the concentration is part of the official title) is specially provided for the management of opioid addicts; it is coloured green and formulated to prevent injection.31
29 From Maurer D W, Vogel V H 1962 Narcotics and narcotic addiction. Thomas, Springfield, Illinois. Courtesy of the authors and publisher.
30 For a general account, see: Drug Misuse and Dependence — Guidelines on Clinical Management. HMSO, London, 1999.
31 It has x 2.5 the strength of Methadone Linctus, for cough (yellow or brown); they must not be confused.
Buprenorphine is an alternative for it also has a long duration of action but it both stimulates and blocks the p-receptor (i.e. it is a partial agonist) and can provoke withdrawal symptoms in patients taking opioid in high dose. Buprenorphine is appears to have less euphoriant effect than morphine. It is unkind, because it is unnecessary, to use an antagonist as a diagnostic test in suspected addicts but naltrexone, a pure antagonist, blocks the opioid euphoriant effect and may be used to prevent relapse in former addicts (see p. 341).
Nonopioid. The withdrawal syndrome is also treatable with nonopioid drugs. Lofexidine inhibits sympathetic autonomic outflow by its agonist action on central presynaptic a2-a d renocep tors and so reduces the effects of noradrenergic hyperactivity (see above). It is similar to clonidine (see p. 482) but less likely to cause hypotension. Evidence indicates that lofexidine is as effective as methadone in withdrawal supervised in residential or community settings; having no 'street value' it is not liable to be traded.
A withdrawal syndrome occurs in the newborn of dependent mothers. It is important not to attempt to reduce the mother's use of opioid late in pregnancy, as a more severe and unpredictable neonatal withdrawal syndrome may result.
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