25 March 2003

What causes addiction / Practical issues in prison entries and exits / S8 approvals

Tues 25 March 2003

"What causes addiction - and does it matter?" Dr Richard Matthews.

"Practical issues in prison entries and exits - a new scheme is trialed" Dr Gilbert Whitton.

"Proposed new on-line, web based interface for S8 approvals". Ms Kanan Gandecha, Pharmaceutical Services Branch, NSW Health.

Chair Dr Andrew Byrne.

Dear Colleagues, Dr Richard Matthews has a wealth of knowledge about the history of drug use as well as the philosophy and attendant mayhem in attempts to control it. He reminded us that despite the popularity of drugs over the centuries, only the last 100 years have seen a variety of psychoactive drugs available to most citizens in western countries. For the first time in history the poor could be well fed and have excess income for mind altering drugs which are now major world trade commodities.

We were reminded of the history of the 'big three' legal drugs: caffeine, alcohol and tobacco, followed by the 'big three' illicits stimulants, opiates and cannabis. It is only when three factors coincide that drug use 'takes off': availability, low price and peer pressure. This appears to apply to illicits as much as legal drugs. Dr Matthews pointed out the interesting history of futile attempts to ban the various drugs including tobacco and coffee. Even draconian efforts such as decapitation did not prevent their use! Only today, with taxation, education, warnings and restricted places where smoking is allowed, we have seen substantial reductions in consumption. John Mills essay "On Liberty" was quoted in which sane adults were said to have the sovereign rights over their bodies (and thus what they consumed).

We were told the Coca Cola story in context of the temperance movement from the mid-1800s which saw alcohol as the major evil, ignoring patent medicines and tonics such as cola. Various combinations of caffeine, cocaine, alcohol and other drugs were purveyed to the delectation of Victorian era consumers. The caffeine was originally obtained from the coca nut but subsequently using more economical 'sweepings' from tea processing plants.

Following the Madame Butterfly story, US troops were encouraged to take Coca Cola wherever they went including world wars and other regional conflicts, often selling the drink at a loss (a 'nickel' or 5 cents per bottle).

We also had a lesson in the meaning of the term 'addiction' from the Latin 'ad' meaning 'to' or 'towards' and 'dicere' the verb 'to declare'. From the word's origin we glean the element of a lack of control as the individual is "declared towards" consuming the drug, despite other dissuading factors. This term could be applied equally to behaviours such as gambling, sex or shopping. We know that the ancients were familiar with the addictive properties of opium from the writings of Galen and others.

Keats, Byron, King George IV, William Wilberforce, Thomas de Qunicey were just a few of the 19th century notables who used opiates, largely laudanum. It was only with the invention of the hypodermic syringe that the major acute dangers of opiates (morphine) became evident. Yet, still at high prices, intravenous opioids did not become generally popular for another 100 years.

Regards drug use generally, Dr Matthews used a graph of two parallel alcohol studies to show that three groups emerge of (1) dabblers, (2) 'accelerators' and (3) heavy users. It is this last group consumes 80% of the total drug supply and also has most of the morbidity. Why this occurs is speculative, but its significance is obvious regarding harm reduction interventions such as needle services, methadone treatment, injecting rooms etcetera. The final conclusion was that we do not know the full story of the cause of addiction, but that its quest probably DOES matter.

Rather than just looking at drug use in prison entrants, Dr Matthews started with psychiatric symptomatology. He showed elegantly from a large study that anxiety, psychosis, depression and mental defection were each greatly over represented when compared with community findings. Predictably we also saw drug and alcohol use/dependency far more common and especially polydrug use in prison inmates. Several of the figures were more than 100-fold the community prevalence! Dr Matthews questioned whether prison was always the right place for such folk who in a previous age may have not used drugs at all, and if they did, may not have been subject to the risks attended by the illicit market.

Next, and on the same topic, Dr Gilbert Whitton let us know about a new scheme to facilitate prison inmates moving to community methadone, buprenorphine [and ?naltrexone] prescription on discharge. The new scheme will operate in regional areas rather than the current centralised system. Area coordinators will liaise with GPs, clinics and hospital to attempt to facilitate transfers without interrupting treatment which is so often a cause of relapse, reoffending and reincarceration. We were told by the PSB representative that any GP in NSW can prescribe temporarily for such a patient if appropriate authority is obtained (Tel 02 9879 5246). This would require that the patient is already on stable treatment and this is to be continued in a supervised manner with a 'mentor' arrangement either with another community specialist or the original prison prescriber. Presumably take-home doses would be very limited if available at all in such cases initially.

Ms Kanan Gandecha next told us to expect major changes in PSB approvals in the next few months as web-based application trials come to the field. Security will be similar to that used for internet banking with a 'user name' and ID number for prescribers (the current prescriber number will be used to avoid duplication). Access will be strictly limited to the doctor's own patients, or to clinic patients for clinic managers. Prison medical authorities will be considered as one special group, allowing information to be shared more easily in this special case.

Numerous questions were raised concerning privacy, out of hours access, changing addresses, doses, pick up points, etc. All applications will still need individual pharmacist approval for patient, doctor AND pick up point. This will simplify transfers from methadone to buprenorphine (or vice versa for those unhappy with buprenorphine). PSB processes up to 100 applications per day and attempts to keep to a 24 hours turn around time. These include methadone, buprenorphine, stimulants (for ADD) and opioids for chronic pain which are all handled by only 6 pharmacists. Urgent applications, such as priority cases of pregnancy, HIV are always processed first, sometimes within 2 hours or even less.

comments by Andrew Byrne ..

3 March 2003

Anticraving drugs - boring or breakthrough?

Anticraving drugs - boring or breakthrough?" Dr Stephen Jurd at Concord Seminar Series 4th Feb 2003.

Dr Stephen Jurd spoke eloquently about the use of anti-craving drugs foralcohol dependence at our first Concord Dependency Seminar for 2003.

We were reminded of the history of this field and the poor uptake of the two approved drugs, acamprosate and naltrexone both in Australia and overseas. Well under 5% of target subjects are currently being prescribed the drugs for reasons which are not at all clear.

Our speaker detailed the now copious research data on these medications individually as well as one very recent trial using both together, a non-approved but promising innovation.
Dr Jurd described his own personal way of choosing whether to try acamprosate or naltrexone initially. He feels that one can score most alcoholics between two extremes, one end tending to drink to get the blood levels up to high levels and attain pleasurable experiences, the other end drinking to maintain a blood level, thereby avoiding unpleasant and negative feelings, including physical/mental withdrawals. From opiate research we know quite a deal about the pleasure centres, opioid receptors, naltrexone blockers, etcetera, which probably dominate as a causal mechanism in the first type of alcohol dependent subjects. The GABA and glutamate systems are in a rough balance, modulating the level of arousal in the CNS. Acamprosate is active at both GABA and glutamate receptors, in an opposite way to alcohol (decreasing glutamate activity and increasing GABA activity). Thus naltrexone decreases the positive feelings associated with alcohol and acamprosate reduces the negative feelings associated with the lack ofalcohol. Naltrexone decreases positive reinforcement and caproate probably decreases negative reinforcement.

The research on naltrexone and acamprosate has been performed in numerous ways in different countries. A common end point in American studies was 'time to relapse' where this was defined as '5 standard drinks on one day' or '5 drinking days' (of any quantity). [And to confuse further, an American 'standard' drink has 15g alcohol, not 10!]

Some European acamprosate research used 'time to first drink' (ANY drink) which made interpretation and comparison more difficult but all trials showed substantially higher numbers retained in treatment and abstinent at 3 months with approximately double the numbers being retained. Graphs of treatment population 'decay' are most impressive, showing an even greater response to both drugs used simultaneously. Outcomes have varied widely in different studies, but there have been so many positive studies that it is beyond doubt that these drugs exert an active effect, presumably on cravings.

The Concord audience was also reminded of the definition of the "intention to treat" research principle: It is a preferable way to analyse outcomes in research studies to include the results from all subjects included in the study, not just those who complete the study. In this way, the survival curve displaying the decay of sobriety over the months will have different sample sizes at each point on the graph. Starting say, with 50 subjects in each of the active and placebo group, after a week 4 may have dropped out of the placebo group and 5 may have dropped out the active drug group. What is compared in the graphing of the results is the PROPORTION of sober subjects at 1 week, say 40 out of 45 (or .89) and the PROPORTION of sober subjects in the placebo group, say 35 out of 46 (or .76). Thus at each point on the graph, all available data are used. As each subject drops out, the denominator decreases.

The anti-serotonin (5HT) drug ondansetron (Zofran) seems to act in a manner opposite to SSRI drugs (which had negative effects in alcoholics in the small number of trials so far performed). Ondansetron doses are modest, being only a fraction of the usual anti-emetic dose of 4mg (300µg taken twice daily). Further studies on this are needed before it could be accepted as a standard alcoholism treatment. The drug appears to be more effective for the "genetic" type of alcoholism rather than the later onset 'reactive' type.

'Rimonabant' is a French-developed cannabis receptor blocker. It seems to have some effect on alcohol cravings in animals but human research is still quite limited.

General practice was the ideal setting to implement these new drug treatments. Both naltrexone and acamprosate are available on the PBS for alcohol dependence when the patient is 'in a treatment program' (such as a general practice setting) - one month supply and repeats allowed. Naltrexone is a simple once daily administration with few side effects in alcoholics. It is contraindicated with opioid analgesics, unlike acamprosate which needs to be taken as two tablets, three times daily. Acamprosate equally has a low side effect profile and few significant drug interactions. The important issue of when to stop therapy was also broached - without a general consensus. Since most relapses occurin the first 2 to 3 months, by 6-12 months it is probably safe to rely on non-drug means to maintain abstinence in most patients.

We should always remember to utilise support services such as self help groups, counselling and psychological services and liver clinics when appropriate.

comments by Andrew Byrne ..