Concord Dependency Seminars were previously published at

20 November 2007

Advances in assessment and treatments for infection with hepatitis C virus (HCV)

Concord Seminar 20th November 2007

Presenter: Professor Greg Dore, Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research.
Subject: Advances in assessment and treatments for infection with hepatitis C virus (HCV).

Topics: HCV epidemiology; treatment assessment; HCV treatment among methadone patients and current injecting drug users (IDU); strategies to improve HCV treatment outcomes; advances in HCV treatment and new research.

Although there has been a drop in annual HCV notifications in Australia from 15,000 in the mid 1990s to 13,000 recently, it is unsure how much of this reflects a fall in incidence (new infections) and thus a success for existing harm reduction policies. As most HCV infections in injecting drug users (IDU) occur within the first few years of injecting, some more significant indicators may be reductions in new HCV notifications in the 15-19 year age group, and in HCV prevalence in young male IDUs attending needle syringe programs (NSPs) from 2001-2006. Such figures do indeed show a marked reduction, which is reassuring that overall notifications should decline further.

It is possible that the lack of a fall in HCV prevalence in young female IDUs may reflect their "going second" in shared injecting situations, and/or sometimes having older male partners already at higher risk of having HCV.

IDUs still constituted the majority (62%) of all acute or newly acquired infections in Australia (n = 474 in 2006), however this may be an underestimate as the source of infection is reported as unknown in 15%, and sexual in 5% (sexual transmission may occur where sexual practices involve blood but is unlikely in most "vanilla" sexual encounters / relationships). Tattoos account for about 8% and occupational exposure 2.5% of new cases.

Overall HCV seroprevalence in people attending NSP remains high at 65%, and is somewhat higher again (75%) in MMT/BMT populations: ie about 30,000 of the circa 40,000 people in opioid replacement treatment in Australia. Of these, probably about 20,000 (50%) have chronic HCV (RNA-positive), about 10% of the total in Australia, making this an important point of access for HCV treatment.

Mortality among people with HCV in Australia has a bimodal distribution, in the 5th and 8th decades of life, the former largely related to drug-related deaths among IDUs and the latter liver disease-related deaths in people born overseas, in HCV endemic areas. Liver disease-related deaths have risen since 1999, a trend perhaps "unmasked" by a fall of direct drug-related deaths as a result of the "heroin shortage".

With cases of HCV cirrhosis in Australia predicted to rise to 12,000 by 2010, and twice that number by 2020, an aim is to be treating 6,000 people/year for HCV. Since April 2006, when the liver biopsy requirement for interferon-based treatment was dropped, treatment figures have risen from about 2,000 to 3,000/year. Liver biopsy was a major disincentive for many people.

Sustained viral response SVR (persisting absence of viral RNA 6 months after treatment) is usually considered a cure of the viral infection, although not necessarily of the underlying liver damage. Occasional later relapses of HCV may represent reinfection with HCV in IDU. Over the last decade response rates to interferon-based treatment have improved, from about 10% SVR for interferon monotherapy to overall to over 60% SVR for combined pegylated interferon/ribavirin (PEG-IFN/RBV), ranging from 50 – 80% depending on genotype.

Early studies of PEG-IFN·2a/RBV showed benefit of longer treatment (48 versus 24 weeks) and bodyweight-adjusted ribavirin dosing (up to 1200mg/day) for genotype 1, but not for genotypes 2 and 3. While early viral response (EVR) - defined as RNA undetectable or >99% decline in viral load at 12 weeks - increases the chances of SVR for genotype 1 to 72%, failure to achieve EVR almost inevitably predicts treatment failure.

The bottom line for treatment is: 24 weeks PEG-IFN/RBV for genotypes 2 and 3; 48 weeks for genotype 1 if the person achieves EVR at 12 weeks. There is no evidence of any difference in efficacy between PEG-IFN·2a (Roche) and PEG-IFN·2b (Schering-Plough).

Recent analysis suggests that people with genotype 1 who have a Rapid Viral Response (RVR) - HCV RNA undetectable at 4 weeks - may do just as well with 24 weeks as 48 weeks of PEG-IFN·2a/RBV, achieving SVR rates above 80%.

At St Vincent’s Hospital in Darlinghurst, treatment completion rates rose from 55% 2000-02 to 74% in 2003-04, with drops in treatment discontinuations due to both non-response and to toxicity. This appears a trend to improvements in delivery of treatment.

Results of treatment in current injectors are comparable to results among non injectors, and abstinence from IDU is not a pre-condition for subsidised treatment in Australia: nor are stage of fibrosis (was pre-2006); elevated ALT (was pre-2006); the presence of symptoms; low alcohol intake.

There is some evidence of poorer treatment outcomes in people who continue to drink alcohol, but whether this is related to worsened treatment adherence or effects on viral replication is unclear.

The current conditions for subsidised treatment eligibility in Australia (S100 Criteria) are:
· 18 years or older
· No evidence of de-compensated cirrhosis
· Must have chronic HCV infection (>6 months)
· Use double contraception where the patient is either a woman of child-bearing years or their male partner.
· No prior IFN-based HCV treatment

Subsidised treatment costs the patient about A$30/month, (A$5/month for concession card holders) and this is probably as cheap as anywhere in the world.

To be balanced against the curative potential of PEG-IFN/RBV are its toxicity (flu-like symptoms, depression, anaemia, lethargy) and the requirement for contraception during and 6 months following treatment. Apart from treatment eligibility, the stage of liver disease and prognosis the genotype and viral load, presence of co-morbidities, and work and family obligations have to be considered in treatment decision-making. There needs to be at least some treatment willingness and relative socio-behavioural stability, however with persistence and good support people with relative treatment contraindications can often be successfully brought through treatment.

Greg Dore advocates some targeting of individuals with higher risk of progressive disease:
Higher likelihood of cirrhosis is predicted by:
· older age (> 40 years)
· duration of infection > 20 years
· heavy alcohol intake
· HIV or chronic HBV coinfection
· peripheral stigmata of CLD (spider naevi, palmar erythema)
· impaired hepatic synthetic function (low albumin, prolonged PT)
· AST / ALT ratio > 1.0
· AST / platelet ratio > 1.0 (<0.5 very unlikely to have cirrhosis)

At the Byrne Surgery, about 50% of people with chronic HCV met similar criteria for higher risk of HCV progression, and have been specifically targeted for treatment, with 27 people having been treated since 2003. Of 20 liver biopsies among these higher risk people, 18 had at least moderate liver fibrosis.

Although HIV and HBV co-infection are relatively uncommon in people with HCV infection, they are definite indicators of higher risk, and in many cases HCV treatment should be undertaken before HIV or HBV treatment.

Phase II trials suggest benefit from triple therapies of IFN/RBV with protease inhibitors for chronic HCV and Phase II trials are due to start soon.

Acute HCV can be treated with interferon monotherapy, with SVR rates of 80-90% in 3 months treatment, unless there is HIV co-infection or HCV genotype 1 with a high viral load. However, as about 25% of people spontaneously clear the virus (generally in the first 3 months after infection but up to 6 months and even later in a few cases) treatment of acute infection is usually deferred at least 3 months.

Although sustained viral response rates at the Byrne surgery are high (71% overall, 81% for genotype 2/3) this is a case showing that things are not always so effective. This long-term MMT patient received HCV antiviral treatment in the setting of micronodular cirrhosis, Genotype 1a/1b, viral load 360,000 and pre-treatment alcohol use of 30-60g/day. This patient was overweight 105kg, a smoker (10 cigs/day) with shortness of breath on exertion, chronic airflow limitation (not taking medications), hypertension (Enalapril), probable ischaemic heart disease (chest tightness on stress test but no ECG changes; echocardiogram: LVH with moderate dilatation), osteoarthritis (diclofenac prn), a history of peptic ulcer disease (uses omeprazole prn).

Despite these relative contraindications to treatment, this patient ceased drinking alcohol, and started combination treatment with IFN.2a/RBV, achieving rapid viral response (<600 ie qualitative RNA assay) at 5 weeks. RBV dose started with 1200mg/day and reducing to 800mg/day as haemoglobin dropped under 100, and was stopped for 5 weeks when the patient suffered severe nose bleeds (with normal BP 130/80; prothrombin time 1.1 and platelets acceptable at 81). Diclofenac was ceased, and ENT review showed a large vessel on the septum which was cauterised, packed with Chloromycetin for 3 days, with ongoing Vaseline use.

After the patient had stoically endured 36 weeks of IFN.2a/RBV, and in view of the apparent rapid viral response, treatment was stopped at week 36, sadly with a rapid ALT and viral ‘flare’. The patient has since maintained alcohol abstinence and long term low dose interferon treatment is being considered.

Issues arising from this case were the feasibility of treatment of "brittle" patients; drying of the nasal mucosa with the IFN/RBV; the pros and cons of NSAIDS for osteoarthritis in this situation; the possibility of viral escape with the interruption to RBV treatment and the wisdom of the decision to stop treatment early; whether endoscopy might have been done to exclude oesophageal varices before treatment; the benefits of going on the front foot in treating HCV in substance dependent people, who may rise to the challenge by achieving abstinence (in this case alcohol abstinence).

Other questions arising in the second half:

What about treating people with persistently high-normal ALT? A: there is some discussion about whether ALT reference ranges should be lowered, especially for women. A single normal ALT measurement is not helpful, as ALT typically waxes and wanes in chronic HCV, so ongoing monitoring at least is required. Although one would rather have a persistently lowish than a persistently very high ALT, ALT correlates poorly with disease activity, and the duration of HCV is an important consideration in assessing risk of disease progression.

What is the role of abdominal ultrasound in assessing chronic HCV? A: mainly to exclude portal hypertension. Greg Dore often does not order this test. Newer methods for assessing fibrosis/cirrhosis by measuring the echo ‘stiffness’ of the liver may make ultrasound more useful.

Summary by Richard Hallinan, Greg Dore, Andrew Byrne.

25 September 2007

Withdrawal management and detoxification-with a focus on complicated patients.

Concord Seminar 25 September 2007

Presenter: Dr Joanne Ferguson, FRANZCP, FAChAM, staff specialist psychiatrist, Rozelle Hospital. Medical Director, McKinnon Unit.

Topic: Withdrawal management and detoxification-with a focus on complicated patients.

Dr Ferguson stressed that the McKinnon Unit is not a “detoxification” ward but a medical unit which manages drug and alcohol withdrawals. The term detoxification is commonly used to refer to "chemicals, drugs, and food additives in the processed foods that we eat....", so that the general public, as well as our patients, may conceptualise drug withdrawal as a removal of such toxins: bringing to mind colonic irrigation, detox diets like Lemon Detox, herbal laxatives and high-fibre diets eliminating caffeine, meat and processed food, and associated treatments such as lymphatic drainage and massage.

Dr Ferguson used clinical cases to illustrate principle and pitfalls of withdrawal management. Since detoxification is often undertaken in private with minimal problems and no interventions at all, she chose to deal with the more complicated cases such as those with dual diagnosis, dual or triple dependency and/or chronic infections.

The first case was a 47 year old labourer who had relapsed after 3 years opioid abstinence. On presentation he was using MS Contin (slow-release morphine) 100mg to 500mg injected each day, to a maximum of up to 800mg in the 16 hrs before admission, with no withdrawal symptoms. He was also taking 10-15 x 5mg diazepam tabs daily (50-75mg daily). He was agitated and tremulous on arrival at the detox unit.

The early symptoms and signs of enlarged pupils (possibly due to general sympathomimetic arousal), irritability, and anxiety were attributed to benzodiazepine withdrawal, where onset of symptoms is typically after 16 hours or so. Tremor is unusual as a symptom of opioid withdrawal, and might help point to benzodiazepine withdrawal.

The benzodiazepine withdrawal regime at McKinnon Unit is to give 20mg diazepam 2nd hourly, to a maximum of 80mg in 24 hours, reducing to 60mg daily, then 35mg daily, 20mg daily then nil. Dr Ferguson told us that formal scoring of benzodiazepine withdrawal has not been shown to have any predictive value.

Regarding opiate withdrawal there are usually early symptoms/signs such as enlarged pupils, sweating, pallor, agitation, goose flesh, lacrimation and runny nose. After that, nausea, melancholia and hyperalgesia can occur. At 36-48 hours, abdominal cramps, nausea, diarrhoea, mild leg aches are seen. By this stage, the enlarged pupils usually settle. Beyond this time, at 48-72 hours, there is more prominent aching of the leg and back muscles, abdominal pain and diarrhoea.

For opiate withdrawals at McKinnon Unit the regimen is to give buprenorphine sub-lingual tablets 4mg +4mg+4mg in the first 24 hours. However, with a poor response to this drug initially, he needed a further 4mg making 16mg in the first day off heroin. (Buprenorphine qid dosing has more to do with service related issues than evidence base).

In this case the patient suffered a protracted withdrawal syndrome, with the need to reintroduce buprenorphine on day 11. This was probably due to the mixed withdrawal syndrome, and possibly not adequately treating the opioid withdrawals early enough: it may be buprenorphine doesn't quite have the "grunt" to provide adequate symptom control in some cases.
The second case was a 24 year old methamphetamine-dependent man with schizophrenia, who lived with his family and was on disability support pension. He was taking Seroquel (quetiapine) 600mg bd, Solian (amisolpride) 800mg daily, Cipramil (citalopram) 40 mg daily, and had also been smoking a gram of “ice” daily for 8 months and taking Xanax (alprazolam) 2mg bd – prescribed by a GP.

Withdrawal symptoms of agitation, hallucinations and religious preoccupation settled with diazepam 60mg in 24 hours. He then slept, was quiet and left at day 4 against medical advice, but clearly not happy with continuing treatment (and diazepam had been reduced by then).
Dr Ferguson posed the question of whether there is a withdrawal period from amphetamine use at all, or whether it is just a recovery period. Hence symptomatic treatment for agitation and sleeplessness may be provided with medications such as chlorpromazine, olanzapine and/or diazepam: there is some evidence of amphetamine users accessing olanzepine, as well as the more commonly available benzodiazepines, for self-medication of the amphetamine "come-down". The only thing that will help profound listlessness would be to extend the stimulant use. However, this is always self limited.

The third case was a man aged 45 yrs with hep C, cirrhosis, diabetes and leg ulcers who had been drinking 90 to 120g alcohol daily with up to 15 x 5mg tabs diazepam daily. Single and on a pension, he was looking after his 13yo old daughter. He was a heavy tobacco smoker as well as using injected heroin every 2 weeks on pay days.

The case illustrated how comorbid medical problems can have similar signs to alcohol withdrawal, including elevation of body temperature, and how to discriminate with a proper medical evaluation including blood counts and biochemical measures. Other issues were the need for nicotine replacement for tobacco withdrawal; whether agitation might be due to nicotine replacement or nicotine withdrawal; a possible preference for oxazepam over diazepam for severe liver failure with impaired hepatic drug metabolism (risk of over-sedation from accumulation of diazepam); a lower need for diazepam when unwell or drowsy.
A mild Alcohol Withdrawal Syndrome may not need any medication within the first 24 hours, after 2-3 days symptoms of anxiety, sweaty, headaches, insomnia, tremor, mild hypertension and tachycardia may be present. “Generally symptoms are mild and require little in way of medication” however medication eases withdrawal and improves outcome - diazepam and thiamine are the mainstay. There is no evidence of benefit from more than 100mg thiamine daily, however at least the first dose should be given intramuscularly, as after bouts of heavy alcohol use there may be chronic or acute diarrhoea, and oral absorption is often poor. For severe intoxication/withdrawal, for example for drinkers of methylated spirits, 100mg thiamine should be given intramuscularly for at least 3 days.

More severe symptoms are dehydration, diarrhoea, anorexia, nausea, vomiting and weakness and very severe cases may have hypertension (diastolic of 120mmHg or greater can require antihypertensives) panic attacks, marked tremors, fever (however true fever is rare unless with an infectious cause). Seizures and delirium are a sign of treatment failure and should not occur when proper medical treatment available.

Alcohol withdrawals can occur with relatively high blood alcohol levels in heavy drinkers, including those who have reduced their use - Dr Ferguson has seen a case of alcohol withdrawal with a BAL of 0.17, so one needs to assess baseline use and more recent use.
Alcohol Withdrawal Scales (AWS) are subjective, with infection/fever and other illnesses as potential confounders, and need to be used thoughtfully and in context. Further, AWS has poor correlation with BP/pulse. Providing diazepam only when AWS >5 means people can be significantly uncomfortable before can get treatment. A kinder alternative may be to treat as soon as the BP is elevated or at the first sign of tremor.

The issue of using vigabantrin (Sabril) for alcohol withdrawal was raised as it may have fewer side effects but is currently only approved for resistant epilepsy.

The fourth case was of recurrent withdrawal episodes in a 47 year old alcohol and opiate dependent man on pension living alone in a rental flat, a history of depression and hypothyroidism, and more than 10 admissions to hospitals in 12 months, usually through casualty distressed & unable to cope, out of medication in withdrawal, anxious, but also with several falls and injuries, complicated by MRSA infection, and recently shortness of breath with possible myocardial infarction.

After prolonged withdrawals (80mgs diazepam for 3 days then reducing over 10 days) he was unable to go to rehabilitation as he was overwhelmed and unable to organise himself.
Issues raise by this case were: therapeutic nihilism - where feelings of despair, hopelessness in treatment providers augment the client's feelings of guilt, shame and hopelessness; and the ‘GOMER’ (get out of my emergency room) syndrome. The patient had some cognitive impairment but not so much to need involvement of the Guardianship Board to manage his affairs. Under the NSW Inebriates Act there has been a trial at Nepean Hospital of compulsory treatment for 2 weeks, with another 2 weeks following where necessary. Patients can also be sent to gazetted Psychiatric Hospital beds. This is not feasible for the great majority.
In general the patient needs to initiate treatment, and we need to recognise and accept the limits of what we can do, focus on symptom management not demand management and have a clear consensus of treatment aims, an agreed plan of treatment and a opt out phase.

Dr Ferguson described protocols for withdrawal management at Rozelle Hospital.

Opiate dependency: - buprenorphine 8-12 mg sublingual per day for 3-5 days, depending on opiate type and quantity. Reduce to 8/6/4/2/2 for last 2days. Symptomatic relief with metoclopramide (Maxalon), hyosine (Buscopan), diazepam (Valium).

Alcohol: - diazepam (Valium), dose not set, related to dispensing and review issues, maybe 40mg/day and metoclopramide (Maxolon) and antihypertensive.

Cannabis/THC: Symptoms of insomnia, agitation, irritable, appetite change, lasting 1-5 days, for which benzodiazepines - at lower doses than for alcohol withdrawal - , olanzapine (Zyprexa), mirtazapine (Avanza) may be used. There seems to be a consensus not to do inpatient withdrawal for THC, but McKinnon will do it for failed (and documented) outpatient withdrawal.
In order to access their services, there needs to be a phone assessment of demographics (do they live in the right area?); drug use and co morbidities; negotiation of a treatment plan (which MAY include withdrawal medication options) and then articulation of the plan: for admission (the person must phone daily at 7am until they can secure a place for admission); and/or outpatient appointments; documentation for MMT/BMT; mental health assessment; and/or other requirements eg plans for subsequent rehabilitation programmes.

Some predictors of failure ambulatory treatment (as an outpatient) are (1) poor support of abstinence; (2) poor housing (or no housing); (3) multiple drug use, including withdrawal from one substance and use of others (except nicotine); (4) or severe symptoms of withdrawal.

The question was raised why drug and alcohol practitioners in the community seldom have any joy "referring" their patients liaising directly with the staff of "detox" units, and do not receive discharge summaries as from most other hospital services. The answer may lie in the historical development of hospital drug and alcohol services using a psychiatric care model, with a primary client orientation and team based case, as well as possibly some resistance among nursing staff to perceived medical paternalism.

In the second half there were a few case vignettes and selected scenarios:
"I went into hospital to come off alcohol and benzos, and they just gave me Normison and sent me home on the 3rd day ...". This was a 41yo woman with history of alcohol withdrawal fits, alcoholic hepatitis. Some questions raised were:

1. If someone has a history of having fits while taking benzodiazepines, do they need admission for withdrawal management? A. not necessarily

2. Why does anyone need to go into a detox unit to come off benzodiazepines? Surely you can just change them over to diazepam and reduce the dose, in the community. A: supervision issues.
Evidently this patient’s symptoms were assessed as mild in the first 48 hours, predicting little risk of complicated benzodiazepine withdrawal. However it appears to be an early discharge for alcohol withdrawal, depending on the alcohol use history given.

"I get fits when I stop alcohol, but I'm not going back to that detox place - can't you just give me some Valium, Doc?" This was a 54 yo man on methadone, with hepatitis C, cirrhosis and ascites, presenting to a doctor in the community, with blood alcohol 0.06 and withdrawal symptoms of agitation and marked tremor. As alcohol withdrawal is dangerous, Dr Ferguson considered it medically strongly indicated to give some diazepam. However, some doctors may feels apprehensive about medico-legal consequences of giving diazepam to an intoxicated patient outside a supervised setting. It may be safest in small quantities, especially if supervised at the surgery, clinic or pharmacy.

"I need to go somewhere to come off cannabis, but the rehab won't take me because I'm on methadone, and the detox unit say they don't do cannabis withdrawal...." - it was agreed that some people may need to remove themselves from a high exposure environment to stop cannabis use, and this may be difficult when the person in on MMT. Some "detox" units offer this service, while for others it is considered low priority.

Andrew Byrne posed the question of when and why detoxification units started giving opiates to opiate addicts. Previously it was rather unusual, if not unheard of, rather like giving hospital brandy to alcoholics who were drying out. This changed the nature of the treatment from detoxification to ‘re-toxification’ in many or even most opiate admissions. This can even be the case in those intent on immediate abstinence. Especially with a very long acting drug such as buprenorphine, it ensures that detoxification does not even start until a few days after leaving the ward, quite the opposite of the traditional position. Was the decision to use buprenorphine in such situations taken to just to keep the patients quiet? Why not use methadone or morphine? Were there commercial considerations? The practice may offer patients a ‘taste’ of a possible maintenance treatments yet this they could just as easily obtain as out-patients, and most opiate addicts have tried such approaches. Dr Ferguson had no answer, nor did anyone else, it seems. This dramatic change in treatment policy seems to have happened without any discussion or most importantly, input from drug addicts themselves. The only justification we were told is that compliance and retention are now better, yet these were not tied to logical and practical patient goals, most notably opiate abstinence.

Summary written by Richard Hallinan, Andrew Byrne, Judith Meldrum with help from Dr Joanne Ferguson’s power point presentation.

31 July 2007

Personality Disorders. 31 July 2007

Concord Dependency Seminar 31 July 2007.


Dr Glenys Dore, Senior Staff Specialist Psychiatrist, NSCCAHS

In this seminar Dr Dore introduced us to what is sometimes a “no go zone” for health professionals involved in addiction treatment: Personality Disorders (PDs).

People with Personality Disorders are “The Patients Psychiatrists Dislike” (Lewis & Appleby Br J Psych 1988), and workers in drug and alcohol will recognise these feelings: these patients are seen as difficult to manage, unlikely to arouse sympathy, annoying, not deserving of health resources, noncompliant, not accepting advice, having poor prognosis, their suicide attempts as “attention-seeking’ rather than genuine, their requests for admission as manipulative.

Therefore, a Personality Disorder diagnosis may be seen as derogatory, pejorative and stigmatising. “What is conveyed…. is that the patient is difficult and probably unpleasant” (Gunn & Robertson Psychological Medicine 1976), with their symptoms seen as less genuine (Slavney & McHugh 1974; Thompson & Goldberg 1987).

Before focusing on Antisocial PD and Borderline PD, the most common diagnoses in substance using populations, Dr Dore traced some of the development of ideas about what we now call personality.

Hippocrates identified four elements in nature with four corresponding substances in human beings: Air, with Blood; Water, with Phlegm; Fire, with Yellow bile; Earth with Black bile. Galen later identified four corresponding “temperaments”: from blood, the Sanguine (confident, hopeful); from Phlegm, the phlegmatic (dull, sluggish); from bile, the Choleric (passionate) and from Black bile, Melancholic.

Eysenck neatly resolved Galen’s four temperaments into two dimensions: introversion-extroversion along one axis and stable-unstable along the other. In this model, the “sanguine” person was extroverted and stable; the "phlegmatic" person stable but introverted; the "choleric" person extraverted and unstable; the "melancholic" person introverted and unstable (the psychotic person emerged out of this combination).

Others have suggested a three or four dimensional approach. Cloninger’s model of personality, has four distinct “traits” of Temperament (Harm avoidance, Novelty seeking, Reward dependence and Persistence) and three “traits” of Character (Self-directedness, Cooperativeness, Self-transcendence). Temperament comprises basic emotions, the emotional core of personality, early emotional and behavioural dispositions whereas Character “mental self government”, “what a person makes of himself or herself intentionally”.

For example, one of your correspondents is by temperament harm avoiding, novelty shy, aloof (not needing cuddles) and persistent……another almost the opposite. Both, of course, have Self-directed, Cooperative and Self-transcendent characters!

DSM-IV is concerned less with theories and more with practical empirical descriptions. Thus, it uses a categorical rather than Dimensional approach, with 3 clusters - Cluster A, Odd or Eccentric; Cluster B, Dramatic, Erratic or Emotional and Cluster C, Anxious or Fearful - comprising a total of ten personality disorders (and a rag-bag category, as always in DSM, “not otherwise specified”).

Personality Disorders are common in the general population (Antisocial PD = ASPD 4%, Borderline PD = BPD ~ 2%), and especially so in psychiatric populations and people with substance use disorders. Among people with a current alcohol use disorder:
30% have at least 1 PD; people with a current drug use disorder, 50% at least 1 PD. The ATOS study reported 80% of current heroin users with a PD, 33% Antisocial PD, 7% Borderline PD, 38% ASPD + BPD. In this study BPD was strongly related to suicide attempts, needle sharing, overdose risk, polydrug use, depression, psychological distress and poorer treatment outcomes (Darke et al. Drug & Alcohol Dependence 2004). Antisocial PD is associated with earlier onset drug use & IDU, more polydrug use, higher levels HIV risk-taking and poorer social functioning in patients on MMT (Henderson et al 2002 NDARC Monograph No. 49).

Before labelling someone with a personality disorder (like "narcissistic" or "borderline") it is essential to be sure that they meet the general criteria of a personality disorder. Under the mnemonic PPAIIN, the pattern of inner experience & behaviour must be Persistent, Pervasive (with a broad range of personal & social impacts), from Adolescence onwards, causing Impairment, be Inflexible & maladaptive and Not due to mental disorder, medical condition, or substance use.

Before concentrating on ASPD and BPD, Dr Dore introduced us to all the DSM PDs, for which ingenious psychiatry candidates have developed helpful mnemonics (listed in the Supplement to this summary on the Redfern Clinic Website, with some case examples).

In Cluster A, the Odd or Eccentric group, are the Paranoid (Suspicious, Jealous, but not Psychotic or Unlawful); the Schizoid (Unemotional, Cold, Indifferent) and Schizotypal (Odd + Magical Beliefs, Behaviors, not Paranoid) types.

Cluster A PDs have a higher incidence in families of schizophrenia patients, and are often antecedent for Psychotic disorders, including schizophrenia, delusional disorders and schizophreniform disorder. In these people, stress may trigger Brief Reactive Psychosis.

Treatment options for cluster A include low dose antipsychotics and supportive psychotherapy, with openness, consistency, emphasising reality (paranoid), and social skills development (schizoid), and education on the interaction between substance use & psychiatric vulnerability.

In Cluster C, the Anxious or Fearful group, are the Avoidant (Needs People But Fears Relationships); Dependent (Needs Relationships, Indecisive, Fears Abandonment) and Obsessive-Compulsive (Rigid, Perfectionist + Inefficient) types. The Passive-Aggressive PD (Negative Attitudes with Passive Resistance to Demands) was dropped from DSM-IV.

Remember that Cluster-C PD are not the same as anxiety disorders, although these may co-exist. Anxiety disorders may respond to specific therapies.

In Cluster B, the Dramatic, Erratic or Emotional group, are the ASPD (Aggressive, Unlawful, Impulsive); Borderline (Unstable, Chaotic, Impulsive, not Aggressive or Unlawful), Narcissistic (Self-Centered, Entitled, Lacks Empathy But Not Unlawful or Chaotic), and Histrionic (Dramatic, Seductive But not Chaotic) types.

Many people will recognise the “narcissistic rage” of a person typically fragile at their core, the demands of specialness and entitlement belying a sense of inner inferiority. It was asked without irony how common Narcissistic PD is among CEOs. Sadly few people with Narcissistic PD go into psychotherapy, few improve over time. Histrionic PD might present as almost hypomanic.

Briefly the DSM criteria for ASPD are: the individual is at least age 18 years, with evidence of Conduct Disorder with onset before age 15 years, and a pervasive pattern of disregard for and violation of the rights of others occurring since age 15 years, not exclusively during the course of Schizophrenia or a Manic Episode.

As a general exclusion, the behaviours should not be better explained by another disorder, including a substance use disorder. ASPD may be over-diagnosed in SUD populations, because drug seeking behaviours, especially for illegal drugs, are likely to be considered “antisocial”.

ASPD is more common in 1st-degree relatives of ASPD individuals, is associated with ADHD; the related Conduct Disorder is associated with erratic or inconsistent parenting and neglect. After 30 years of age there tends to be reduced antisocial behaviour (crime, promiscuity) and reduced substance use.

Dr Dore gave the example of a man who had a history of fights, truancy, theft, near expulsion from school, drug use and dealing, addiction to heroin, benzodiazepines, cannabis, with alcohol use, and by age 19, three counts of murder. When seen at age 36 yrs, he was married, with a child, and much settled.

Heroin users with ASPD respond as well as other heroin users to opioid pharmacotherapy (similar retention in treatment, methadone dosage, improvement in heroin use) however with poorer social functioning (Darke et al 1996; Darke et al 1994; Gill et al 1992; Rouser et al 1994)

Spot the diagnosis: “On return from your last holiday, your patient informed you that she smashed up her goldfish bowl and flushed her much-loved goldfish down the toilet, killing them. She has since replaced them.”

Marsha Linehan (1993), the guru of Dialectical Behavior Therapy, gives us an unforgettable image:

“Borderline individuals are the psychological equivalent of the 3rd-degree burn patient. They simply have, so to speak, no emotional skin. Even the slightest touch or movement can create immense suffering….”

Briefly the DSM criteria for Borderline PD are: A pervasive pattern of instability of interpersonal relationships, self-image and affects, and marked impulsivity beginning by early adulthood, which may include: frantic efforts to avoid real or imagined abandonment; unstable and intense interpersonal relationships alternating between extremes of idealization and devaluation; impulsiveness in spending, sex, substance abuse, shoplifting, reckless driving, binge eating ; recurrent suicidal threats, gestures, or behaviour, or self-mutilating behaviour; intense episodic dysphoria, irritability, or anxiety; chronic feelings of emptiness; inappropriate, intense anger or lack of control of anger; transient, stress-related severe dissociative symptoms or paranoid ideation. (see supplement for full criteria

People with BPD may suffer from an almost murderous rage. Does “cutting” serve as emotional release or self punishment? Their feelings may swing pendulum like between love and hate, the pedestal and resentment. There is a poor sense of identity, of who/what they are.

BPD is characterised by recurrent suicidal threats, gestures, or behaviour, or self-mutilating behaviour, and although 90% improve despite multiple suicidal episodes, the stark reality is that 10% will complete suicide. Like ASPD, BPD tends to improve with age: by age 35 - 40 years: 75% have close to normal function, with less impulsivity (suicidality, self mutilation), better interpersonal relationships (less stormy relationships, less devaluation/sadism/manipulation) and people learn how to avoid emotional triggers. (Paris J. Canadian Medical Association Journal 2005)

In managing patients with PDs, especially BPD, it is important to bear in mind the concept of Transference, whereby unresolved feelings about important figures from the patient’s past are revealed in the patient’s transference towards the therapist.

Common defense mechanisms allow the person to defend against threatening or anxiety-provoking situations: splitting, idealisation, denigration, externalisation, projection, denial, acting out, repression.

If this seems too high falutin, we can at least identify the tactics. The person may stone- wall (allows no choice other than his/her position), attack (“You’re not the caring doctor I thought”....“I’ll take you to HCCC”....“I’ll kill myself”) or trick (manipulating the facts, making surprise demands) (from Ury William. Getting Past No: Negotiating With Difficult People).

The therapist's counterpart to transference is "Countertransference". They may themselves fall into the role of victim (feeling helpless, worthless, distant, withdrawn), of abuser (getting angry, retaliating, rejecting, cancelling appointments, "throw off program") or the role of rescuer ("only I understand"; unfair criticism of colleagues, extra appointments, late night calls, inappropriate prescribing, even sexual relationship).

In balancing Countertransference, remember there is a "zone of helpfulness" between overinvolvement and underinvolvement.

In managing your reactions, remember people are often trying to provoke reaction - they know your hot buttons. It is tempting to strike back, to break off the relationship, or to give in – the latter rewards bad behaviour, encourages same tactics in future, damages your reputation (weak, soft touch) and may compromise safety

Some tips:

• Try not to react, remain empathic and non-judgmental,
• “Go to the balcony”, either actually or mentally.
• “Step to their side” (you can't reason with a non-receptive patient, give a full respectful hearing
• Acknowledge (don’t dismiss patient as irrational, acknowledge his/her point & feelings, if appropriate offer an apology)
• Use active listening (eye contact, empathic, reflective listening, paraphrase, seek clarification
• Buy time to think (pause & say nothing, “rewind the tape, ask for clarification, take time out, delay the decision)
• Try to understand transference-countertransference issues.
• Debrief with colleagues

Some rules for yourself:

• Acknowledge their position, even if don’t agree with it (agree wherever you can)
• Express your views clearly without provoking (acknowledge negative impacts of your decision, acknowledge your differences, speak about your responsibilities, mention duty of care, Guidelines, Dept of Health etc)
• Negotiate a way forward (treatment contracts can help)

The focus of treatment for BPD may be the BPD itself, or co-morbid Axis I, II disorders, and should include safety assessment and risk management.

A suicide/violence risk assessment distinguishes between plan and intention. Watch out for a recent mental state change. Management includes a crisis plan in collaboration with other (clinicians and family), increasing patient responsibility (exploring alternatives to self harm, self soothing techniques), consulting with colleagues if high risk, with medication and/or hospitalisation if needed. It is crucial to document your assessment and plan: remember the pain of writing a "Dear Coroner" letter.

Pharmacotherapies for BPD may be used with the aim of symptomatic relief: for affective dysregulation, impulsive-behavioural dyscontrol, or cognitive perceptual symptoms (suspiciousness, referential thinking, paranoid ideation, illusions, derealisation, depersonalisation, hallucinations). Treatments may include SSRIs or venlafaxine, low dose antipsychotics (higher doses if psychotic), Mood Stabilisers. ECT may be used if there is co-morbid severe axis I depression.

Dialectical Behaviour Therapy is a three pronged approach

• Accepting patients just as they are within a context of trying to teach them to change
• Supportive acceptance; validation
• Confrontation & change strategies (individual or group work towards emotion regulation, improved interpersonal effectiveness, distress tolerance, core mindfulness, self-management skills) (Linehan M. CBT of Borderline PD 1993)

Principles of work with BPD (After Gabard 1994) are

• Establish a stable framework/structure predictable (eg frequency, length sessions)
• Take an active stance: validate, affirm
• Contain the anger & self destructing behaviours (soothe, validate, risk assessment, limit behaviour; problem solve)
• Establish the connection between feeling & actions
• Set limits on problem behaviours
• Maintain a "here & now" focus
• Monitor countertransference feelings
• Risk Management

Dr Dore highly recommended “Getting Past No: Negotiating With Difficult People”, a book by Ury William.

Summary by Richard Hallinan based on the Concord presentation by Dr Glenys Dore.
Supplement with helpful diagnostic mnemonics

Personality disorders (by Dr Glenys Dore) supplementary notes.

Concord Dependency Seminar 31 July 2007.


Dr Glenys Dore, Senior Staff Specialist Psychiatrist, NSCCAHS

Summary Supplement

Paranoid personality disorder: SUSPECT (four criteria)

S (1) Suspicious of others
U (5) Unforgiving (bears grudges)
S (7) Spouse fidelity suspected
P (6) Perceives attacks (and reacts quickly)
E (2) “Enemy or friend” (suspects associates & friends)
C (3) Confiding in others feared
T (4) Threats perceived in benign events

Mrs F complained that people at work disliked her and she contemplated seeking legal advice as she thought they wanted her to leave. She had prolonged disagreements with the pay office about salary and conditions. When she requested a change of appointment with her doctor she “knew” it would be rejected despite it being offered, and complained bitterly about inflexible health professionals” Harari & Meares 2001

Schizoid personality disorder: DISTANT (four criteria)

D (7) Detached or (flattened) affect
I (6) Indifferent to criticism and praise
S (3) Sexual experiences of little interest
T (2) Tasks (activities) done solitary
A (5) Absence of close friends
N (1) Neither desires nor enjoys close relations
T (4) Takes pleasure in few activities

Schizoid personality disorder

Marjorie, a nurse, worked in the night shift in a small hospital. She lived alone with her 6 cats and saw her family only on Christmas Day, an event which she found most anxiety-provoking. Born of elderly parents, she had always been quiet and remote, a compliant child who seemed to need no company. In adult life she found it difficult to understand other people’s need for friends and believed that an emotional life was ‘unnecessary’. Harari & Meares 2001

Schizotypal personality disorder: ME PECULIAR (five criteria)

M (2) Magical thinking or odd beliefs
E (3) Experiences unusual perceptions
P (5) Paranoid ideation
E (7) Eccentric behaviour or appearance
C (6) Constricted (or inappropriate) affect
U (4) Unusual (odd) thinking and speech
L (8) Lacks close friends
I (1) Ideas of reference
A (9) Anxiety in social situations
R (10) Rule out psychotic disorders and pervasive developmental disorder

Avoidant personality disorder: CRINGES (four criteria)

C (2) Certainty (of being liked required before willing to get involved with others)
R (4) Rejection (or criticism) preoccupies one’s thoughts in social situations
I (3) Intimate r’ships (restraint in intimate relationships for fear of being shamed)
N (5) New interpersonal relationships (is inhibited in)
G (1) Gets around occupational activity (involving significant interpersonal contact)
E (7) Embarrassment (potential) prevents new activity or taking personal risks
S (6) Self viewed (as unappealing, inept or inferior)

Dependent personality disorder: RELIANCE (five criteria)

R (1) Reassurance (required for decisions)
E (3) Expressing disagreement difficult (due to fear of loss of support or approval)
L (2) Life responsibilities (needs to have these assumed by others)
I (4) Initiating projects difficult (due to lack pf self confidence)
A (6) Alone (feels helpless and discomfort when alone)
N (5) Nurturance (goes to excessive lengths to obtain nurturance and support)
C (7) Companionship (another relationship is sought urgently when close relationship ends)
E (8) Exaggerated fears of being left to care for self

Obsessive-compulsive personality disorder: LAW FIRMS (four criteria)

L (1) Loses point of activity (due to preoccupation with detail)
A (2) Ability to complete tasks (compromised by perfectionism)
W (5) Worthless objects (unable to discard)
F (3) Friendships (and leisure activities) excluded (due to a preoccupation with work)
I (4) Inflexible, scrupulous, overconscientious (on ethics, values, or morality, not accounted for by religion or culture)
R (6) Reluctant to delegate (unless others submit to exact guidelines)
M (7) Miserly towards self and others
S (8) Stubbornness (and rigidity)

Histrionic personality disorder: PRAISE ME (five criteria)
P (2) Provocative (or sexually seductive) behaviour
R (8) Relationships (considered more intimate than they are)
A (1) Attention (uncomfortable when not the centre of attention)
I (7) Influenced easily
S (5) Style of speech (impressionistic, lacks detail)
E (3) Emotions (rapidly shifting and shallow)
M (4) Made up (physical appearance used to draw attention to self)
E (6) Emotions exaggerated (theatrical)

Narcissistic personality disorder: SPEEECIAL (five criteria)

S (3) Special (believes he or she is special and unique)
P (2) Preoccupied with fantasies (of unlimited success, power, brilliance, beauty or ideal love)
E (8) Envious (of others, or believes others are envious of him/her)
E (5) Entitlement
E (4) Excess admiration required
C (2) Conceited (grandiose sense of self importance)
I (6) Interpersonal exploitation
A (9) Arrogant (haughty)
L (7) Lacks empathy

Antisocial personality disorder: CORRUPT (Three criteria)

C (1) Conformity to law lacking
O (6) Obligations ignored
R (5) Reckless disregard for safety of self or others
R (7) Remorse lacking
U (2) Underhanded (deceitful, lies, cons others)
P (3) Planning insufficient (impulsive)
T (4) Temper (irritable and aggressive)

A Quick Guide to the Personality Disorders (adapted from "DSM Made Easy", an excellent reference tool for the busy clinician!)

"DSM-IV lists 10 personality disorders.... divided into three clusters, A, B, and C........ Five of the 10 have been studied reasonably well and therefore have greater validity than the rest: antisocial, borderline, obsessive-compulsive, schizoid, schizotypal."

Cluster A: "withdrawn, cold, suspicious, or irrational."

Paranoid Personality Disorder:....."distrustful and suspicious of others, whose motives are seen as malevolent."

Schizoid Personality Disorder:..... "isolated from social relationships and shows a restricted emotional range in interpersonal settings."

Schizotypal Personality Disorder:....... "isolation and discomfort with social relationships, as well as perceptual or cognitive distortions and peculiar behaviour."

Cluster B: "dramatic, emotional, and attention-seeking.....moods are labile and often shallow.......often have intense interpersonal conflicts."

Antisocial Personality Disorder:..... "Before age 15, for 12 months or more the patient [satisfied criteria for Conduct Disorder]...repeatedly violated rules, age appropriate societal norms, or the rights of others.... Since age 15, the patient has shown disregard for the rights of others in a variety of situations."

Borderline Personality Disorder: ......"unstable impulse control, interpersonal relationships, moods, and self-image."

Histrionic Personality Disorder: ...... "emotional excess and attention-seeking behaviors are present in a variety of situations"

Cluster C: "anxious and tense, ......... often overcontrolled."

Narcissistic Personality Disorder:...... "grandiosity (fantasized or actual), lack of empathy, and need for admiration"

Avoidant Personality Disorder:........."social inhibition, hypersensitivity to criticism, and feelings of inadequacy are present in a variety of situations"

Dependent Personality Disorder:..... "a need to be taken care of leads to clinging, submissive behaviour and fears of separation that are present in a variety of situations"

Obsessive-Compulsive Personality Disorder:....... "a preoccupation with control, orderliness, and perfection overshadow qualities of efficiency, flexibility, and candour."

Generic Criteria for Personality Disorders

1. A lasting pattern of behaviour and inner experience that markedly deviates from norms of the patient's culture..... evident in at least two of these areas:

• Affect
• Cognition
• Impulse control
• Interpersonal functioning

2. This pattern is fixed and affects many personal and social situations ....[and] causes clinically important distress or impairs work, social, or personal functioning.

3. This pattern has lasted a long time.......with roots in adolescence or young adulthood.

4. It isn't better explained by another mental disorder ......[and] isn't directly caused by a general medical condition or by the use of substances, including medications.

Full Diagnostic Criteria for Borderline Personality Disorder

A pervasive pattern of instability of interpersonal relationships, self-image and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts, as indicated by 5 (or more) of the following:

• Frantic efforts to avoid real or imagined abandonment (do not include suicidal or self-mutilating behaviour covered in criterion 5).

• A pattern of unstable and intense interpersonal relationships characterized by alternating between extremes of idealization and evaluation.

• Identify disturbance: persistent and markedly disturbed, distorted, or unstable self-image or sense of self (eg. feeling like one does not exist or embodies evil).

• Impulsiveness in at least two areas that are potentially self damaging (eg. Spending, sex, substance abuse, shoplifting, reckless driving, binge eating – do not include suicide or self –mutilating behaviour covered in criterion 5).

• Recurrent suicidal threats, gestures, or behaviour, or self-mutilating behaviour.

• Affective instability: marked reactivity of mood (eg. intense episodic dysphoria, irritability, or anxiety) usually lasting a few hours and only rarely more than a few days.

• Chronic feelings of emptiness.

• Inappropriate, intense anger or lack of control of anger (eg. Frequent displays of temper, constant anger, recurrent physical fights).

• Transient, stress-related severe dissociative symptoms or paranoid ideation.

Full Diagnostic criteria for 301.7 Antisocial Personality Disorder

A. There is a pervasive pattern of disregard for and violation of the rights of others occurring since age 15 years, as indicated by three (or more) of the following:

• failure to conform to social norms with respect to lawful behaviours as indicated by repeatedly performing acts that are grounds for arrest
• deceitfulness, as indicated by repeated lying, use of aliases, or conning others for personal profit or pleasure
• impulsivity or failure to plan ahead
• irritability and aggressiveness, as indicated by repeated physical fights or assaults
• reckless disregard for safety of self or others
• consistent irresponsibility, as indicated by repeated failure to sustain consistent work behaviour or honour financial obligations
• lack of remorse, as indicated by being indifferent to or rationalizing having hurt, mistreated, or stolen from another

B. The individual is at least age 18 years.

C. There is evidence of Conduct Disorder with onset before age 15 years.

D. The occurrence of antisocial behaviour is not exclusively during the course of Schizophrenia or a Manic Episode.

22 May 2007

The Interpretation of Urine Toxicology in Dependency Treatment. Principals and Pitfalls.

Concord Seminar 22 May 2007

The Interpretation of Urine Toxicology in Dependency Treatment. Principals and Pitfalls

Speaker: Dr John Lewis, Toxicology Unit, Pacific Laboratory Medicine Services

Dear Colleagues,

Dr Lewis is one of the world’s leading experts in drug testing. His speaking manner combines what T. S. Eliot might have termed a lugubrious drollery with a profound grasp on his subject. It is easy to be light-hearted about ‘piss tests’ but it is also deadly serious if your own job, drivers licence or liberty depend upon such a result.

We were reminded first up what urine testing can NEVER determine with any accuracy: (1) the dose, (2) the time it was taken or (3) the pharmacological effect of any substance being tested.

The most common drug assays they perform are for methadone and metabolites, cannabinoids, opiates, cocaine, benzodiazepines and amphetamines. Barbiturates often omitted these days since their illicit use seems to have ceased for all practical purposes. The term ‘amphetamine type substances’ (ATS) is now superseding ‘sympathomimetic amines’. This group includes dexamphetamine, methylamphetamine, ecstasy (MDMA), methylenedioxyamphetamine (MDA), and other ‘designer’ drugs such as paramethoxyamphetamine (PMA) and their metabolites, but also ephedrine, pseudoephedrine. One needs to know the particular immunoassay ‘kit’ being used to be sure what exactly is detected and at what level.

Laboratories are asked to perform tests both in a clinical setting as well as for forensic, workplace or medico-legal reasons. For clinical purposes a cost effective and fast turn-around time approach is used. This starts with an inexpensive immunoassay which is very sensitive for most of the drugs being tested for, but generally not specific. Hence a negative batch of tests can yield a fast, efficient response to the clinician. Positive immunoassay results for any of the drug groups (or negative for methadone) may indicate further testing, typically using GCMS (gas chromatography/mass spectrometry), which is considered the ‘gold standard’. Although thin layer chromatography (TLC) is not commonly used nowadays, Dr Lewis says it still has a place: it presents information on a large range of drugs to view at a single glance, and is inexpensive. Because the TLC depends upon the human factor of recognising patterns, it is subjective and unless the spot patterns correspond to known medication, confirmatory testing by mass spectrometry is usually conducted. Although it is not used for medico legal work, it still has a place in clinical settings, as an adjunct to mass spectrometry in presumptively identifying a wide range of therapeutic substances not amenable to immunoassay.

In particular cases there will need to be specific tests done, especially for suspected drug use which may not be detected by the usual immunoassays. These include tests for doctors, nurses or other health care workers on conditional registration due to drug use. Such drugs include pethidine, tramadol and the short acting anaesthetic propofol. Abuse of these drugs outside the medical setting is exceptional.

Note that buprenorphine is also hard to detect by simple methods. Although there is an immunoassay for the drug, toxicologists must be aware of possible false positives from a number of unrelated therapeutic substances. However, like methadone, when the dose is taken under supervision such testing is less important than, say, in England where much treatment is unsupervised and testing for the prescribed medication can be crucial in determining compliance and overall stability.

Dr Lewis then detailed the limitations and strengths of modern immunoassays in determining a class of drug but only in two cases can they detect specific metabolites, EDDP (for methadone) and 6-mono acetyl morphine (heroin). The value of a negative test was pointed out. We were reminded that testing was almost pointless in hospital casualty cases: for overdoses, the results are usually not available until either the patient is dead or else recovered. Also, medications are used so routinely and such patients may have injuries necessitating local anaesthetics, dressings, iodine, etc in the course of their treatment in the casualty ward that results are close to meaningless.

Specifically, Dr Lewis said that positive opiate and ATS immunoassays should be taken with caution as there are many causes of false positives. These include poppy seeds, cough mixtures, decongestants and common analgesics. Dr Lewis told us that his own urine remained positive for ‘opiates’ for nine days after a dose of the cough suppressant pholcodine. The main value of these screening tests is when the result is negative. Note that ‘opiate’ immunoassays do not detect the ‘opioids’ methadone, buprenorphine, pethidine and others. Oxycodone has only a very weak response to “opiate” immunoassays.

We were then shown the plates used for thin layer chromatography and a list of 20 common drugs which can be definitively determined using this method (eg. morphine, codeine, oxazepam, pseudo-ephedrine, paracetamol and nicotine). GCMS was then described in response to a question from the floor. In essence it appears that there are two properties of each substance which are identified in the method, causing a unique fingerprint from the two derived figures. It is more expensive than other methods, but more accurate and specific, being able to detect both the original base compound as well as ‘derivatised’ products.

Then we had a brief tutorial on the use of testing for alcohol consumption. Everyone knows about breath testing, but 5% of alcohol is excreted in the urine and there is a direct correlation between plasma and urine alcohol concentration of 1.3:1. However, due to the short half life of alcohol, such testing is only of any use within hours of the drug use. And, as with other drugs, a certain level could be associated with a small amount of drug used very recently, or equally, a large amount used quite some time before.

There are also unexpected false positives, including a case Dr Lewis described where urine from a diabetic in a rehabilitation facility had undergone fermentation (probably by yeasts) before being tested; the calculated blood alcohol concentration (0.34) would have been lethal. A less ‘gross’ error might not have been discovered, and this would have led to the automatic expulsion of the person from the rehab facility.

Tests for cannabis are of limited value since, for most, its use is not relevant to the treatment or supervision being given. Hence Dr Lewis only performs cannabis tests when specifically requested, such as in patients being treated for cannabis dependence, to assess progress.

We were then taken through some metabolic pathways. Heroin breaks down within minutes into 6-acetyl morphine, then to morphine. This then is broken down into morphine-6 or -3 glucuronide which are excreted. Codeine is largely conjugated into codeine-6 glucuronide, but importantly, a small proportion is transformed into morphine. A positive test for morphine can therefore sometimes occur due to codeine use (but not the other way around). A warning: most tests underestimate the amount of codeine in urine, as the metabolite codeine-6 glucuronide is hard to "bust" into codeine, which can be detected. It is important to know the relative amounts of morphine and codeine in a urine sample as the ratios affect correct interpretation as to what may or may not have been ingested.

Diazepam is broken down into another active metabolite, oxazepam. This can occur via two intermediaries, nordiazepam and temazepam. Most of the common sedatives and related drugs such as clobazam will show up as benzos on the initial immunoassay. However, specific confirmatory testing must be done when clobazam is used in therapeutic trials to test against ‘street’ benzos.

Stimulants were then covered including the new definition of ice in an age of global warming (ice-bergs and all!). Amphetamine was first synthesised by the Germans in 1887. It was heavily marketed in the US in the 1930s as ‘Benzedrine’. Methylamphetamine is easier to manufacture, especially if one has the base product pseudoephedrine. We were then told that the latest ‘craze’ for stimulants is purely based on stronger, highly purified drug being available in the form of ‘crystal meth’ or ‘ice’. Methylamphetamine powder is a salt, "crystal" a highly purified salt, and "base" is an oil. Urine testing cannot distinguish between them as these are the same drug. While Dr Lewis’ lab has found 2005 was the year with highest mean amphetamine levels, in 2006 the maximum levels found each week continued to climb to being 5 fold the 2003 levels. While these are dramatic findings, it is hard to know their significance overall except to imply that some users are taking very large amounts of methylamphetamine, viz, “ice”.

Cannabis has many metabolites which are detected on screening, and confirmed with carboxy –THC on GCMS. It is very lipophilic, and gets stored in the fat cells of the body. Cannabinoid urine tests may be negative within a few hours of a single smoke; daily use may take many days, and heavy use a month or more. If a high level is found then it is easy to know that there is continuous use. Carboxy-THC: creatinine ratios can indicate increasing or decreasing use (see case vignettes below).

Then there was a discussion about laboratory ‘cut-offs’ which are essential for legal purposes, but less meaningful for clinical purposes, except to reduce the numbers of false positives. Cut-offs are also necessarily somewhat arbitrary, like the drink driving limits - and can vary from place to place or from time to time. Currently 50ng/ml is used for immunoassays of cannabinoids, and 15 ng/ml for the specific GCMS for carboxy-THC (plus or minus a figure for lab uncertainty; this means an actual cut off of around 18-19 ng/ml). Dr Lewis believes there is a case for higher cut-offs to be used for cannabinoids, to identify substantial cannabis use, rather than low level or more importantly residual drug from previous heavy use.

Some case vignettes in the second half illustrated common problems. Three patients with positive immunoassay for opiates claimed only to have taken codeine-based analgesics. One had codeine and morphine on GCMS, and this could be explained by metabolism of codeine to morphine, or other sources or morphine such as poppy seeds, morphine sulphate etc. Another had urine positive for morphine, and negative for codeine: this could occur if there was extensive metabolism of codeine to morphine (for example by cytochrome CYP2D6 ultrarapid metabolisers) and especially if the laboratory test underestimated the amount of codeine (see above). In the last case, urine was positive for morphine and monoacetyl-morphine: the latter can only come from heroin use.

In a case of roadside drug testing, a woman justified her positive salivary cannabis test by saying "I never smoke pot, but my partner smokes it all the time". Dr Lewis explained that this test does not pick up metabolites of THC, only the parent drug, and is not very sensitive, missing a large proportion of cannabis users (as reported by the European ROSITA study). Thus passive smoking could not cause a positive test. A man on methadone, who had not had a positive urine test for many years, blamed his positive urine cannabinoid test on his partner, who ‘smoked 30 cones each day’. A positive immunoassay test result is unlikely to be a result of passive inhalation. It is more likely be a false positive due to other medication, cross contamination or else laboratory error.

Dr Lewis described the benefits of using carboxy-THC:creatinine levels to help allow for variation in urine concentrations due to level of hydration. Cases were shown from the Drug Court, where declining THC:creatinine ratios were consistent with ongoing abstinence; in another case a spike in ration of THC:creatinine led to punitive action, but might have been explained by the person going to the gym, and mobilising cannabinoids stored in fat cells.

Another case from the Drug Court showed how the sequence of appearance or disappearance of diazepam metabolites (nordiazepam, oxazepam and temazepam) could be used to make inferences about recent diazepam use. In this case, as in almost every example discussed, Dr Lewis was able to give examples of exceptions, where other causes than the most obvious might account for the result. So urine tests should never be interpreted uncritically by untrained people.

In another case, a worker was suspended for producing "dilute urine" (wrongly described as a "false negative urine test") because of low creatinine urine (1.4 mmol/L), and allegedly told he would need to produce two urine tests with creatinine higher than 5 mmol/L. However, this worker's serum creatinine was low owing to lean body build, while urea, electrolytes, specific gravity, osmolality were consistent with physiological urine. THC:creatinine ratios might help adjust for hydration (some people deliberately drink lots of water to dilute their urine) but could also discriminate against people with naturally low creatinine. A urine creatinine level as low as 0.9 mmol/L is physiologically achievable. Below this suggests the likelihood, and below 0.5 mmol/L the near certainty, of external interference with the sample, usually meaning dilution after urination.

Laboratories and clinicians need to be careful with the information they give as employers may misinterpret loose terminology.

Comments by Andrew Byrne, Richard Hallinan and Judith Meldrum, from Dr Lewis’ talk and power point presentation.

20 March 2007

Methadone side effects, separating fact and fiction.

Concord Dependency Seminar, Tuesday 20 March, 2007

"Methadone side effects, separating fact and fiction".

The evening began with Dr Adam Winstock's overview of a recent study of about 1000 patients on methadone and buprenorphine, suggesting high rates of side effects: sweating, sexual dysfunction, sedation and constipation. Patients wanted help with these issues but many had not discussed them with their opioid prescriber. The biggest problem regarded as a consequence of methadone / buprenorphine was dental difficulties. Surprisingly there were few differences in side effect profiles between either medication, and other than sedation there was no clear dose relationship with any side effects, nor a relationship with the duration of treatment.

Since side effects are problematic and can be reduced with appropriate treatment in some cases, and since many patients’ attributions are incorrect, managing side effects should be more frequently addressed in consultations according to Dr Winstock. Fewer side effects may lead to better retention and improved health generally in the drug dependent population.

Dr Richard Hallinan then looked at hormonal, sexual and dental problems in methadone maintenance treatment (MMT), starting with some quite early studies. In 1970, over 200 MMT patients retrospectively compared their current complaints with their time before MMT (Bloom and Butcher 1970). 80% on MMT (versus 3% before MMT) complained of weight gain; 40% (versus 15%) of increased use of alcohol; 70% (versus 58%) constipation; 32% (versus 12%) numbness of hands and feet; and 60% (versus 49%) had difficulty with ejaculation.

However, a prospective study of 180 men and women before and during MMT (Garbutt and Goldstein, 1972) showed improvements in most physical symptoms during MMT, including aches and pains in muscles, bones and joints, craving, sweating, anorexia and nausea, headaches and insomnia, with little change in constipation, impotence and climax problems.

What are addicts like before MMT? Wilczek et al (2002) reported test results on over 100 men and women before they started MMT, finding low haemoglobin (24%), elevated CRP (25%), low testosterone levels (in males, 63%). Imaging methods revealed hepatomegaly in 28% and splenomegaly in 27% with liver steatosis in 15%.

Does methadone cause obesity? Szpanowska-Wohn et al (2004) reported statistically significant growth of body weight, in 48 men and women during 9 months of MMT, with fewer underweight and more overweight or obese people. Given the prevalence of overweight and obesity in the general community, it is however not clear whether this is a return to "societal norms" or a direct causal effect.

Do people on MMT have sexual dysfunction? Compared with 41 normal controls, Teusch et al 1995 found 37 MMT men and women differed significantly in sexual interest, emotional arousal, physiological arousal, performance and orgasm satisfaction. However as noted above, they may be better or little different from their time on heroin.

A number of studies have shown that plasma testosterone is lower in male heroin addicts than controls. Many studies in animals and humans have shown that opioids suppress testosterone, acting at the level of the hypothalamus to reduce secretion of gonadotrophins: "hypogonadotrophic hypogonadism". Amenorrhoea is common in women using heroin, and menstrual cycles tend to normalise during MMT (Schmittner et al 2005).

However, studies of men on prescribed opioids have given contradictory results. Only 10% of 92 MMT men reported by Brown et al (2005) had low testosterone, but low mean testosterone was reported in 54 men taking oral sustained-action opioids for chronic pain (Daniell, 2002); and also in 37 men on methadone maintenance (Bliesener et al 1995) while the mean testosterone level of buprenorphine-treated patients did not differ from that of healthy controls. Bliesener et al suggest buprenorphine might be preferred over methadone for this reason. Daniell has called for androgen replacement for men taking opioids who have low testosterone, citing low energy, muscle weakness, sexual dysfunction and higher risk of osteoporosis.

Wilczek and Stepan (2003) reported on bone mineral density (BMD) and metabolism before and during MMT, finding that heroin addicts had low average BMD; after one year of MMT, BMD remained unchanged, although osteo-resorption and -formation markers normalised. Recently Kim et al 2006 have reported osteoporosis in 35% and osteopenia in 48% of 92 patients in MMT, with male gender, lower weight and heavy alcohol as risk factors. However this study group may have been at higher risk (eg high rates of HIV medication and the possibility of self-selection in the study recruitment).

On the available evidence, screening for osteoporosis probably should be targeted, rather than universal, in men and women on MMT: heavy alcohol smoking, poor diet, history of low stress fractures, and hypogonadism are risk factors to consider.

Two studies have reported reduced sperm quality in men on MMT and in heroin addicts: Cicero et al in 1975, but in these studies controls were lacking or poorly matched and alcohol may have been a confounder.

Several studies have shown high caries rate and severe periodontal disease in heroin addicts, and excessive intake of food with a high sugar content is common (Scheutz 1995, Zador et al 1996). Although drug addicts often only realized how poor their dental health had become during periods of abstinence (Scheutz, 1995), caries increments were higher among people on methadone maintenance than current heroin abusers, but not statistically significant (Scheutz, 1984).

Opioids, like antidepressants, anti-cholinergics and HIV medications, may cause xerostomia (dry mouth) and this is considered a risk factor for dental disease (see Concord Seminar 20 May 2003. Dental problems in addiction treatment subjects: does methadone rot teeth? Can we prevent dental decay? Dr Peter Foltyn).

Gingivitis is a reversible inflammatory disease of the periodontal tissues, and periodontitis, in addition, involves destruction of the supporting structures of teeth. Smokers are more susceptible to periodontal diseases, and alcoholics compared with 100 non-addicts exhibited intensive dental caries (Gerlach and Wolters 1977). Poor periodontal health with reduced salivary flow has also been reported in people with chronic HCV, and use of cannabinoids has been associated with increased xerostomia (dry mouth) and severe gingivitis (Fazzi et al 1999).

Despite all of these potential confounders to a relationship between opioids (prescribed or illicit) and dental and peridontal disease, a detailed epidemiological study with control for confounders is still lacking. In the meantime, it is reasonable to give the following oral health advice to people on opioid replacement treatment:

"Give up smoking. Brush your gums, not just the teeth. Make sure your diet is balanced and avoid excessive high sugar foods. If dry mouth is a problem, try oral lubricants (like 'Oral Balance') especially at night, and dry mouth toothpaste and mouthwash (eg 'Biotene' toothpaste + mouthwash). Avoid alcohol-based mouthwashes, which dry the mouth."

Dr Andrew Byrne then spoke on constipation, sweating and prolonged QT in methadone maintenance.

Constipation and sweating are common in patients on methadone, probably more commonly at high doses but also at quite low doses such as 30mg daily. The symptoms are usually of a minor nature and require no more than sympathy, explanation and reassurance. Occasionally these may be severe enough to need further attention. If they are ignored, some patients may even drop out of treatment.

Constipation can mean different things to different people so clarification is needed about frequency, consistency, bleeding, haemorrhoids, bloating, diet, etc. There is no single approach but we should always address exercise, fluids, diet and consider laxatives or suppositories/enemas if other measures fail. Specialists advise avoiding bowel irritants such as senna and related compounds since these can cause colitis in long-term use. Luminal agents such as Magnesium sulphate, mannitol, lactulose, etc can be used while there are combination products which some patients find acceptable (Movacol, Microlax, Coloxyl with danthron).

Sweating likewise can occasionally be so troublesome that patients need help. There may be saturated clothing in the daytime while at night, sheets and pyjamas may need changing due to excessive sweating from methadone. The precise cause is unknown: candidates include hypothalamic and autonomic mechanisms, and histamine release. There may be multiple aetiologies since some get it after the dose, others when in withdrawal and other still at unpredictable times. It may also be seasonal and can respond to reassurance and slight dose reductions.

Two medications may be worth trying. The drug loratadine (‘Claratyne’) is an over-the-counter ‘non-drowsy’ antihistamine. A stronger and more specific medication is the anticholinergic drug propantheline (‘Pro-banthine’). The latter may cause dry mouth, dizziness and other autonomic side effects so patients may wish to cut it in two (which needs a pill cutter as the tablet is not scored).

Dr Byrne then pointed out that purported methadone related cardiac conduction problems were like a Miss Marple mystery without a body. After 40 years of successful use across the world it would be unlikely that a serious side effect would suddenly be recognised. And, despite the initial report in 2002 by Krantz and colleagues of 17 non-fatal cases on high doses (average 400mg daily), there has still been no series of cases reported in regular maintenance patients.

Prolonged QT and ventricular fibrillation remain rare complications of many common medications, often also involving serious concurrent metabolic and structural disturbances. Krantz, who has written about the possible dangers of prolonged QT interval in Lancet, does not recommend ECG in new MMT patients. The NSW Health Department has advised performing a cardiac assessment including electrocardiogram for patients who are being considered for high dose methadone (>200mg daily). This would seem to be a reasonable precaution.

In the second half, several case "vignettes" were presented, including three cases of low testosterone in opioid-treated men.

Gert, 41 yo, on MMT with a current dose 70 mg, was found on screening to have low total testosterone: 5.5 nmol/L; his testosterone dropped to 3.7 nmol/L despite methadone dose reductions to 55mg. Luteinising hormone (LH) was low. His BMI was 29. Abdominal ultrasound showed fatty liver. His dual energy X-ray densitometry (DEXA) scan showed osteoporosis, with lumbar T-score -2.6.

He was seen by an endocrinologist, and on questioning admitted to low energy, low libido, increasing erectile dysfunction, hot flushes, weight gain in last 12 months. Prostate examination and specific antigen (PSA) were normal. He was started on androgen replacement with "Androderm" patches, with resolution of his hot flushes, low energy, low libido, and erectile dysfunction. However patches caused skin irritation, and he much preferred "Sustanon" injections, and later testosterone transdermal gel. At follow up DEXA a year later, lumbar T-score had improved to -1.9.

This brief presentation was filled in after questions from the audience: Gert's testicular volumes were normal. Liver function tests, full blood count, thyroid function tests and prolactin were normal. Visual fields were normal (cerebral CT was not done). The main reason for treatment in this case was osteoporosis (not sexual dysfunction, which the patient had not actually complained about). Testosterone assays were performed in the morning, as recommended.

We were reminded of the Australian Endocrine Society for androgen replacement treatment: for persistent hypogonadism (at least two morning testosterone levels below 8.0 nmol/L); if there are symptoms of low energy, mood, muscle strength, sexual dysfunction, especially if there is osteopenia, osteoporosis. Prefer testosterone and its esters to synthetic androgens, check the prostate and PSA in men >40yo. Beware the marked placebo effect that often occurs with androgen replacement, which may lead to subsequent disappointment.

It was pointed out that haemochromatosis should have been considered in the differential diagnosis (the endocrinologist in this case notes that haemochromatosis and pituitary tumour are the 2 classic exclusions for the diagnosis of hypogonadotrophic hypogonadism. In this case no other clinical features of haemochromatosis were present, but hypogonadism caused by iron deposits in the pituitary can present in isolation from other features of haemochromatosis. Iron studies were normal in this patient).

The second case was Ben, a 31 year old labourer from regional NSW, who had been on buprenorphine maintenance the last 2 years, after previous MMT. His alcohol use was very heavy from his late teens, he injected amphetamines from age 21 and heroin from age 23. He was HIV, HBV and HCV seronegative and liver function tests were normal.

With his buprenorphine dose 8-12mg daily, he was prescribed sildenafil as he had formed a new relationship and complained of erectile problems. His total testosterone was low at 7.3 nmol/L with low LH, and he was referred to sexual health physician. Penile Doppler was normal, and there was a poor erectile response to a prostaglandin challenge. Follow up testosterone was 8.7 nmol/L. He was advised that his erectile dysfunction was psychogenic.

Ben continued to have erectile dysfunction, and resented needing PDE-5 inhibitors. He reduced his buprenorphine dose precipitously, then returned needing dose supplements. Continuing reductions were accompanied by a rise in testosterone in to the high normal range, but erectile dysfunction remained intermittently a problem.

A year later his wife blamed buprenorphine for their failure to conceive, insisting he come off treatment, despite by now normal testosterone. Ben was was worried about his sperm count. After counseling, they attended a fertility clinic. Ben's sperm count was normal, his wife's ovarian cyst was removed, and ‘they’ become pregnant 8 weeks later.

After reducing his dose to 0.4 mg, Ben came off buprenorphine with protracted symptoms requiring mirtazepine, clonidine, and eventually temazepam. He was off BMT for the birth of his son, but relapsed into heroin use 8 months later.

This case illustrated the risk that sexual dysfunction may destabilise opioid replacement treatment; that buprenorphine can be associated with low testosterone and sexual dysfunction; that androgen replacement is not necessarily needed whenever testosterone is low.

Bill was a 56 yo man, on MMT continuously since 1991, his current dose 65mg. He had injected heroin since age 22. His current alcohol use was 70-140g/day, and he smoked 10 cigarettes/day. He had chronic back pain after a minor injury in 1999, and fractured his right humerus after slipping in a puddle 2002. He was admitted to hospital with (?aspiration) pneumonia in 2000.

Bill had Dupuytrens contractures, spiders, palmar erythema. His blood tests showed elevated GGT and AST, normal ALT, low platelets (130), normal haemoglobin but macrocytosis. He was HCV seropositive and repeatedly HCV-RNA negative.

His morning total testosterone was 10.0 nmol/L and 7.2 nmol/L on two occasions (normal 12-36). With his worsening kyphosis, X rays showed wedge fractures of the thoracic spine, and loss of height in lumbar spine. DEXA showed osteoporosis (T score -4.1 spine and -3.0 at hip). Serum folate was low at 3.7 (>7.0).

Bill was referred to an endocrinologist, who noted his low BMI (18.8). Coeliac screen, and 25-OH Vitamin D were normal. A repeat total testosterone was 12.1 nmol/L.
After dental review, bisphosphonate was prescribed, with calcium supplements and folate.

Among the ‘messages’ of this case: the likely importance of alcohol, smoking and dietary factors in the genesis of osteoporosis in this man; the need to check other causes of macrocytosis in an alcoholic; and again, the need not to rush in with androgen replacement.

Finally there was a case vignette, to put things in perspective: “I've been on a hundred mils of methadone a day for 25 years and I'm as fit as a fiddle! Most of the people who I started using with are long since dead. I consider methadone has kept me alive, and is the best tonic ever invented.”

Summary written by R. Hallinan, A. Winstock and A Byrne.

31 January 2007

Amphetamine/Stimulant Use: Presentations, complications, interventions.

Concord Seminar Tuesday 30 January 2007

Amphetamine/Stimulant Use: Presentations, complications, interventions.

Speakers: Dr Alex Wodak, Director of the Alcohol and Drug Service, and Ms Tarra Adam, Stimulant Treatment Program, Clinical Program Manager, St Vincent’s Hospital, Darlinghurst. Chaired by Dr Bob Batey.

Dear Colleagues,

Dr Wodak gave an overview of increasing amphetamine use around the world. In 2002, of 91 countries, 56 showed increasing "abuse" of amphetamines, and 11 showed a decrease. There was an increase in amphetamine labs in the years from 1998 to 2004 of 300 to 18,000, with production of Amphetamine Type Substances (ATS) rising from 312 tons to 480 (UNODCCP Global Illicit Drug Trends 2002). Among 15-64 year olds in 2006 there was a prevalence of ATS use in Asia of 0.6%, Oceania of 3%, and Global 0.6% (UNDCP 2006 World Drug Report).

Australian Institute of Health and Welfare statistics show an increase in admissions for amphetamine-related psychosis, from approximately 1000 in 1999/2000 to approximately 1600 in 2003/2004. There has probably been a further increase since then, however the increases have been patchy across the country, with increases in NSW and Victoria being less than other states (a large increase in the year 1999 can be attributed to the change from ICD 9 to ICD 10 definitions).

Recently there has been a trend away from plant based substances to chemical based drugs due to efforts to avoid both the vagaries of weather, and improved surveillance by air and satellite.

To get an idea of the size of the problem in economic terms Dr Wodak pointed out that the size of the illicit "drug industry" in the UK was about the same as British Airways.

Regarding the cost effectiveness of treatment, there have not been any studies specifically looking at amphetamines but it is more cost effective to spend money on cocaine drug treatment than on drug law enforcement (Rydell, Everingham. Controlling Cocaine: Supply Versus Demand Programs, RAND, 1994.) Because of similarities to cocaine, these conclusions may be also relevant to amphetamines.

In the words of the economist Milton Friedman: "So long as large sums of money are involved - and they are bound to be if drugs are illegal - it is literally hopeless to expect to end the traffic or even to reduce seriously its scope. In drugs, as in other areas, persuasion and example are likely to be far more effective than the use of force to shape others in our image."

Dr Wodak described typical presentations of amphetamine use: a psychosis that looks like schizophrenia; severe, even suicidal, depression; aggressive behaviour; strokes, hypertension, and arrhythmias; possibly risky sex including HIV risk; infections from injecting drug use including HCV, septicaemia, bacterial endocarditis; and general "social catastrophes" - financial problems, lost jobs and broken relationships, and gambling problems.

No specific regimen has been found to be better or worse than any other for withdrawal management, as amphetamine withdrawal is not well understood.

Cochrane reviews have found evidence about the treatment for amphetamine psychosis is limited: medications of interest are conventional antipsychotics, newer antipsychotics and benzodiazepines. An injection of "anti-psychotic drugs can help relieve the symptoms of amphetamine psychosis within an hour, but there is not enough evidence to show what can help after that".

Among psychosocial interventions for amphetamine dependence, motivational interviewing and cognitive behavioural therapy show promise. Most in the audience had not used the excellent recommended handbook by Baker, Kay-Lambkin, Lee, Claire and Jenner. “A Brief Cognitive Behavioural Intervention for Regular Amphetamine Users” Department of Health and Ageing 2003 - downloadable from the web:$FILE/cognitive_intervention.pdf
Among non-agonist pharmacological treatments for amphetamine dependence, 30-40 different drugs have been evaluated but none really found to be helpful (see Cochrane Review).

Setting the context for agonist pharmacological treatments, Dr Wodak gave the following overview: some amphetamine, especially methamphetamine, users become very chaotic, very volatile, and some become violent. As they may develop paranoia or psychosis, so engaging patients often takes longer, and may be much harder than with other substance dependent patients. They need access to prompt, effective mental health support, and most respond very positively to psychosocial interventions. However a few people with severe intractable use may need Amphetamine Substitution Treatment (AST) in combination with psychosocial interventions.

We were pointed to two reviews of the numerous studies of Amphetamine Substitution Treatment (dating from Griffith Edward’s first study in the 1960s, which gave negative results).
· Shearer J, Sherman J, Wodak A, van Beek I. Substitution therapy for amphetamine users. Drug and Alcohol Review 2002; 21 (2), 179-185.
· Grabowski J, Shearer J, Merrill J, Negus S. Agonist-like replacement pharmacotherapy for stimulant abuse and dependence. Addictive Behaviors. 29 (2004); 1439-1464.
These reviews show that, comparable to the situation for methadone in the 1970s, there is reasonable evidence for the effectiveness and safety of AST. It may be not needed for as high a percentage, nor as long, as for heroin dependent people who need methadone.

Dr Wodak reminded us of the principles of drug substitution treatment:

1. to replace: a short acting drug with a longer action one; an illegal drug with a legal drug; an injectable drug with an oral drug; and
2. to stabilise, counsel, and then where ever possible wean off, as in nicotine replacement, and opioid substitution treatment.

The NSW Department of Health established Stimulant Treatment Programmes in November 2006 at St Vincent’s Hospital, Darlinghurst and in the Hunter New England region. These programmes offer psychosocial interventions but for severe and refractory cases which meet strict criteria, trials are using immediate release dexamphetamine, as slow release amphetamine (which would be preferable) is not yet licensed for use in Australia. There will be daily supervised dosing of 60mg maximum, only for people with severe intractable problems, with small numbers of about 30 per year in each centre. The programmes are being independently evaluated.

The selection criteria are very strict, as Dr Wodak believes it is wiser to start such a treatment with strict limits and later liberalise it if appropriate, rather than "let the genie out of the bottle" too soon.

The power of substitution treatment has been shown in Zurich, where there has been saturation treatment with methadone and other opioids (including prescribed heroin), accompanied by a marked decrease in heroin use, drug overdose, crime and heroin seizures by police, and an 82% reduction in new heroin users from 850 in 1990 to only 150 in 2002. (Nordt, Stohler. Lancet 2006 367 1830-34).

Another benefit may be if ATS acts like a carrot, getting people with problems to ask for help. A number of people on the waiting list for ATS at St Vincent’s Hospital have improved just with psychosocial interventions while being considered for pharmacotherapy.

Tarra Adam then spoke on her work with amphetamine users at Sydney’s St Vincent’s Hospital. She sees those that present at the hospital with problems related to amphetamine use, or who refer themselves.

Some present with aggression or violence which is out of character and worries them. Many have learnt to manage their use reasonably well, before seeking any treatment.

There is a perception that Alcohol and Drug Services are not for them, and historically these services may have had little to offer. ATS users are often suspicious of the service and whether the service can meet their needs, and may appear to be testing out the therapists, having a strong sense of what they want. Often they wish to be seen in a different area or using a separate entrance, because they are "not like the others".

Amphetamine users do tend to show a different profile, being less impoverished and more educated, motivated but hard to engage, often successful at work with a wide range of social contacts, and in better social circumstances than heroin users. Most are daily users, some injecting 3 times a day, some up to 9 times. The majority of people seen at the St Vincent’s Hospital Stimulant Treatment Program are smoking "crystal". Not many switch between amphetamines and cocaine.

A range of therapies is offered, including Motivational Interviewing, Cognitive Behavioural Therapy, and people may be referred to a “SMART Recovery” group. However CBT may be just too difficult for a person who is chaotic or paranoid, and often experience cognitive impairment during periods of use or whilst in withdrawal. In the early stages of treatment, some people find it difficult to concentrate and connect with how their thoughts and feelings influence their behaviour. In addition, talking about triggers and motivations to change with stimulant users has in our experience, increased people’s craving for the drug and can contribute to ongoing use and/ or relapse. Therefore we concentrate on addressing the wider impact of stimulant use on their sense of self, the impact of use on their relationships, rather than concentrating on the drug use itself.
Therefore, other approaches may be needed, with the aim of trying to engage the person.

Narrative Therapy is an example: here the emphasis is centred on people as the experts in their own lives. It views problems as separate from the person and holds that people come with many skills, beliefs, values and abilities that will assist them to reduce the influence of problems such as stimulants in their lives. People often present to therapy with a problem saturated story that dominates beliefs about themselves and influences the choices they make. Narrative conversations seek out the alternative/ preferred stories –stories that are identified by the person about how they would like to live their lives, what it would mean to them to make these changes and supports them to perform this meaning. The therapist seeks out examples of such stories in their lives which support people to break from the influence of the problems they are facing and create new possibilities for their future by increasing awareness of their skills, beliefs, values, and abilities to reduce the influence of stimulants in their lives. A reference for those interested to know more is "What is Narrative Therapy?" by Alice Morgan (can be ordered from the Dulwich Centre - the link for a summary of her book is:

In the second half, chaired by Dr Bob Batey, a range of case vignettes was discussed.

The first case was a woman who declared "I always shoot speed on my pension day, Doc. It is the only time I ever clean the house … but now all my veins are gone!"

Among the points raised were: possible causes of the exhaustion include following a binge, chronic hepatitis C, and depression. A question was raised about the safety of using antidepressants, including SSRIs, in people who use stimulants, including MDMA. Although this was a theoretical risk, given that these medications and drugs raise monoamine levels in synapses, the expected "epidemic of Serotonin Syndrome has not materialised", as one participant put it. It may be worth suggesting safer ways of administration, as a harm reduction measure, and may be appropriate to refer her for financial management assistance through Centrelink, which offers the Centrepay service for regular payments. It was generally agreed that she was not suitable for AST, given the intermittent nature of her use.

In the second case, a man announced "After I use crystal meth I turn into somebody else. I thought I knew how to fly and jumped off the balcony two storeys up to save using the stairs. Now I’m in plaster with two fractured heels and I can’t even get up those stairs".

Problems like this occur especially with use of other substances as well, such as benzodiazepines, and often end up in jail, or hospital. Once the person settles they may be able to look at their substance use, especially if they are laid up in hospital. An important question is how worried friends or family can help decrease the risk of harms like this: one response is that health professionals need to help "significant others" who seek help in the first instance by helping them look after themselves.

This was also true for the following case, where flatmates sought advice about a young man who had moved in recently from Darlinghurst where "it was too easy to go out every night". He regularly used "ecstasy", took Ritalin for ADD, also selegiline which he read on a web site was good for ADD. He was often up all night, constantly reorganising his room with his things strewn all over the yard. One day he declared angrily "I know you’ve been in my room snooping around. You let things slip that show that you did it. I wish I had video surveillance up there".

Tarra Adam said this was a typical presentation to the Alcohol and Drug Service at St. Vincent's Hospital, except that usually the person absolutely believes that others were doing the video surveillance.

A comment was that nothing could be taken at face value in this case: neither the ADD diagnosis, the precise substances used, nor any other psychiatric diagnosis.

In the next case, a 32 yo man, injecting ATS for 2 years, said: "I'm using ice every day and I can't pull up. Can you give me something to help me detox? Or can I go to a detox somewhere?" Even though the evidence about the amphetamine withdrawal syndrome is limited and there seems to be little benefit from medications, many "detox" facilities will admit amphetamine users. One rehab allows the person to sleep and then clean up, maintaining good hydrations being very important. As many ATS users prefer benzodiazepines to manage their withdrawal, a case could be made in community practice for dispensing a small amount of diazepam to encourage engagement with treatment in future.

The final case was a 34 yo man on MMT for 7 years, 11 years injecting, probably 10 years chronic HCV with fluctuating elevated ALT. His methadone dose was 110 mg and his total testosterone was 5.0 -7.2 mmol/L on repeated (morning) testing. He continued to inject ATS several times a week throughout MMT, saying otherwise he has no energy. He was little motivated to change his ATS use.

The reasons for this man's lack of energy could include hypogonadism (probably from opioids), chronic hepatitis C, depression, or the effect of amphetamines themselves. Among the approaches could be a trial of methadone reductions or androgen replacement (chronic viral hepatitis is not a contraindication for use of testosterone and its esters, which should be used in preference to synthetic androgens). One could offer antiviral treatment for hepatitis C, which may be a motivation to stop injecting drug use (injecting should not be a contraindication for hepatitis C treatment). a trial of antidepressants may be indicated. These strategies should probably be tried serially rather than simultaneously, to avoid diagnostic confusion in the event of an improvement in energy.

Written by Judith Meldrum and Richard Hallinan based on Dr Wodak’s talk.