Page 104 - Pagetit

4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

BOX 4.2

Use of buprenorphine in treatment of opioid dependence
Whilst much of the work on substitution therapy has focused on methadone,
several new synthetic oral opioids such as LAAM (L-alpha-acetyl-methadol), slow-
release morphine and buprenorphine have been investigated as potential
therapeutic agents in the treatment of opioid dependence. Buprenorphine in
particular has been undergoing extensive clinical testing for treatment of opioid
dependence and is likely to become the medication used in the management of
opioid dependence not only in specialized clinics, but also in primary health care.
Its pharmacological properties and resultant clinical characteristics – especially
its relatively long duration of action and high safety profile – appear certain to
ensure buprenorphine an important place in the overall treatment of opioid
dependence.

Pharmacologically, buprenorphine is a partial agonist at the mu receptor and a
weak antagonist at the kappa receptor. Because it binds tightly to, and dissociates
slowly from these receptors, buprenorphine exhibits an agonist ‘ceiling effect’,
most noticeably in its respiratory depression effect, which accords the medication
a high degree of clinical safety. Its tight binding with slow dissociation from
receptors also provides a blockade for the effects of subsequently-administered
agonists, precipitates withdrawal in patients maintained on a sufficient dose of
full agonist, and provides prolonged duration of action with poor reversibility by
naloxone. Furthermore, buprenorphine’s weak antagonist effect at the kappa
receptor renders it devoid of psychotomimetic effects. Further research has
demonstrated buprenorphine’s limited levels of reinforcing efficacy in comparison
to opioids, and established its ability to suppress heroin self-administration in
opioid-dependent primates and humans.
The formulation containing both buprenorphine and the opioid antagonist naloxone
has been recently introduced for maintenance therapy of opioid dependence.
Adding naloxone to buprenorphine aims at reducing a risk of diversion and injecting
use of prescribed buprenorphine. Over the past decade a series of controlled
clinical trials, using such outcome measures as illicit opiate use, retention in
treatment, craving and global rating of improvement, have substantiated
buprenorphine’s clinical safety and efficacy. When used in opioid substitution
treatment for dependent pregnant women, it appears to be associated with a low
incidence of neonatal withdrawal syndrome. Due to the above features,
buprenorphine is a useful drug in the facilitation of withdrawal from opioids.
Sources: Barnett, Rodgers & Bloch, 2001; Fischer et al., 2000; Ling et al., 1998.

Heroin-assisted treatment of heroin dependence (see Box 4.3) has also
been proposed.
Naloxone and naltrexone are medications that also block the effects of
morphine, heroin and other opiates by acting as antagonists at the opioid
receptors. They are especially useful in preventing relapse because they block

83

Chapter_4 83 19.1.2004, 11:42