3 February 2004

Alcohol anti-craving drugs

Tue 3rd Feb 2004

Prof John Saunders,

A/Prof Kate Conigrave (case histories).

Convened by Dr Richard Hallinan.

"The latest in pharmacotherapies for alcohol dependency: alcohol and the opiate dependent patient."

John Saunders gave us a scholarly and comprehensive overview of the state of play in the field of alcohol dependency and its treatment in our society today. It is estimated that there are over 500,000 alcohol dependent people in Australia of whom a meagre 10% are in some form of treatment (including self-help groups) while only a minuscule 1% are being prescribed anti-craving drugs at any one time. This contrasted dramatically with an estimated 50% of opioid dependent citizens who were in treatment.

The facts and figures on the consequences of alcohol related harms are profound, affecting driving, drowning, suicide, liver disease, domestic violence and beyond. About 90% of the adult population drink (at least occasionally) and up to 20% are engaged in some degree of hazardous drinking. Young men are over represented, especially those from lower socio-economic groups, indigenous communities and other disadvantaged minorities such as mental health patients.

Professor Saunders described alcohol's effects on a range of neurotransmitters including actions on both GABA and glutamate receptors and how it acts through both dopaminergic and endogenous opioid reward pathways. Thus drugs from a variety of quite different classes have been found to have benefits for alcohol dependency. But with limited effects from single drugs, he predicted the possible wider future use of more effective combination therapies. Parallel moves have happened over the years with certain oncology and antiviral treatments, with substantial benefits for their recipients.

Both naltrexone and acamprosate are approved medications for alcohol cravings in Australia. According to metanalysis of numerous placebo controlled trials both treatments work well in preventing relapse and reducing intercurrent drinking. But we were reminded of the draw-backs of metanalyses which may include studies with very different protocols. Controlled research can only ever determine whether one drug is better than another (or placebo) in given circumstances. The studies he quoted seemed to agree that, when taken according to directions, either drug can double the proportion of subjects who are abstinent at 3, 6 and 12 months after commencing treatment. Australian experience seems to confirm the utility of these treatments in the out-patient setting.

There are a number of factors in choosing between these two first line drugs. As a guide, Professor Saunders cited evidence that naltrexone is indicated especially in people who experience strong craving for alcohol after a priming dose. It seems to reduce the likelihood of a lapse progressing to a relapse. On the other hand, acamprosate is indicated especially in those who are susceptible to 'cueing' by their environment or emotions, or whose drinking is triggered by true withdrawal symptoms. Clearly naltrexone in not suitable in those taking opioid or in whom opioid prescription is likely.

Newer work, case reports and single series have shown some promise for using other agents including the 5HT3 antagonist ondansetron (Zofran). In addition, it appears that the use of naltrexone in combination with acamprosate and other drugs can be safe and effective in appropriate cases.

SSRI antidepressants have been found to be unhelpful in alcoholism and they should be reserved for patients who have stopped drinking but still manifest signs of clinical depression. Buspirone was mentioned as having a place in alcohol dependent people with disabling social phobia.

The use of Antabuse (disulfiram) has waned in recent years and as a single agent there would appear to be little favouring its use. According to Professor Saunders it may still have a place an adjunct with other treatments where adequate supervision of doses is always desirable.

It was stressed by both speakers that medication should always be given in the context of a supportive clinical setting with psychosocial interventions, counselling and 'suggested' but not 'obligatory' self help group attendance.

Case Histories

Two interesting case histories were presented by Professor Kate Conigrave regarding alcohol problems in regular methadone patients. Both cases stimulated discussion regarding how to deal with intoxicated patients who present for methadone dosing, and whether it was appropriate to continue treatment at all with its attendant risks. Some clinicians used breath testing kits while others used clinical measures while all clinicians in the audience either refused to give medication or else reduced doses in such patients when intoxication had reached a certain degree.

In one of the cases Professor Saunders raised the possibility of rapid methadone metabolism possibly requiring split-dosing. This was taken up by Kate Conigrave regarding her suggested physical examination 3 and 24 hours after dosing to determine waxing and waning of the opioid effects.

A lack of time prevented further discussion of the place of measuring methadone blood levels in unstable patients, a subject which was covered in previous seminars. However, some clinicians never order methadone levels, stressing the primary importance of clinical assessment in dependent patients who are drinking excessively.

Comments and summary by Andrew Byrne and Richard Hallinan from lecture given and material provided by the above two speakers (JB Saunders, K Conigrave).

Next meeting:

Tuesday 6/04/2004 Chair Dr Gary Swift

Session 1 "At their peril: Cocaine-related deaths in NSW."

Prof Shane Darke, National Drug and Alcohol Research Centre

Session 2 "Forum on takeaway doses."

Prof James Bell, The Langton Centre.