Personality Disorders (Supplement)

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.

Personality Disorders

Concord Dependency Seminar 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 nonjudgmental,

. "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 comorbid 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 comorbid 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.

Note there is also a supplement to this seminar available.

Failure of naltrexone implant reported from Russia.

Dear Colleagues,

Griffith Edwards, long time Addiction editor, once wrote that case reports were of limited value scientifically - and he was right. However, sometimes simple clinical observations can be the start of something big, such as lithium on the positive side (Melbourne) and thalidomide (Sydney) on the negative one.

In this month�s Addiction (July p1164) Krupitsky, Woody and colleagues report on a patient who overcame the artificial blockade from a naltrexone implant, a product which is apparently now registered for use in Russia [1 gram ~ �one month blockade�].

A drug dealer engaged the patient as a courier, knowing that he had had an implant. He assumed that the man could therefore not avail himself of the large quantities of drugs he was to smuggle into a local prison on a regular basis.

After receiving numerous payments in the form of heroin he attempted to �test� the blockade by injecting first 2, then 4, then 8 and then even more �bags� of the illicit heroin. We are told that on the final injection he overdosed and became cyanotic. Having survived, he continued using the by now very large quantities of heroin until it ran out 2 weeks later. Suffering severe withdrawal symptoms, he was then re-admitted for detoxification. It is a mystery that methadone treatment is still illegal in the Russian Federation, yet an unproven formulation of naltrexone is being used by �narcologists�.

Detoxification only rarely results in abstinence for life and it is tragic that relapsing addicts in Russia have little alternative but to return to street opioids.

Doctors who use naltrexone implants in addiction treatment are taking risks both for themselves and their patients. The benefits of naltrexone implants might outweigh their very real dangers, yet no comparative research has yet been published to support their use. Since most return to heroin use at some stage, those recommending naltrexone need to propose strategies to prevent overdoses. After detoxification, there is very low tolerance and thus heightened vulnerability to overdose.

Hulse and Tait, who are usually strong advocates of naltrexone and these days are strong advocates of naltrexone implants, draw attention to another serious problem with naltrexone implants. Because opioids are generally ineffective at normal doses, some patients will die from overdose of combinations of non-opioid drugs (or from spectacularly high doses of opioids as above) (Hulse GK, Tait RJ. Opioid overdose deaths can occur in patients with naltrexone implants. MJA 2007 187;1:54). However, their estimate in the same letter that the mortality of patients on naltrexone implants is only one in 600 patient-years seems a tad optimistic and should not be accepted until replicated by others in well-designed studies. We have to be mindful that naltrexone supporters in Australia and overseas have often �over sold� the benefits while also under-estimating the negatives of naltrexone. Remember 'I woke up cured of heroin addiction' in the Woman's Weekly a decade ago?

Comments by Andrew Byrne ..

Krupitsky EM, Burakov AM, Tsoy MV, Egorova VY, Slavina TY, Grinenko AY, Zvartau EE, Woody GE. Overcoming opioid blockade from depot naltrexone (Prodetoxon�). Addiction 2007 102:1164-5

Hulse GK, Tait RJ. Opioid overdose deaths can occur in patients with naltrexone implants. [response] MJA 2007 187;1:54

Gibson AE, Degenhardt LJ, Hall WD. Opioid overdose deaths can occur in patients with naltrexone implants. MJA 2007 186;3:152-153

June Addiction journal: solid studies but a new 'sting in the tail' like Scorpio.

Dear Colleagues,
It is nice to see the Addiction journal finally giving some prominence to harm reduction. There is an item on secondary benefits of injecting rooms as well as two brief reports questioning current policies and institutions (see below, from Australia and Canada). Compiled by Peter Miller and Susan Savva, the �News and Notes� column has been known to toe the zero tolerance line, even rubbishing those who might question prohibition (eg. Aug 2000) or support medical cannabis.
It is hard to understand why the National Addiction Centre and Society for the Study of Addiction have never conceded the parlous stage of dependency treatments and harm reduction measures in the UK. They both seem to studiously avoid controversy and continue doing �more of the same�. Even to this day, the SSA internet notice board which took about 8 years to get up and running carries no traffic.
Is there no-one in England with enthusiasm for our important and interesting field? Are people so intimidated or embarrassed at previous failures that they have gone underground or moved overseas?

Comment by Andrew Byrne ..

ADDICTION JUNE 2007 "News and Notes"

AUSTRALIAN CRIME COMMISSION CONCLUDES PROHIBITION �NOT EFFECTIVE� [What a surprise!!]

The Age newspaper in Australia features a report [1] on the Federal Parliamentary Joint Committee on the Australian Crime Commission. Their recent �Inquiry into the manufacture, importation and use of amphetamines and other synthetic drugs in Australia� [2] has concluded that: �prohibition, while theoretically a logical and properly intentioned strategy, is not effective�. This conclusion didn�t sit easy with the current Australian government and The Age suggests the sensationalised climate that politicians have to work within makes them fearful of entering a rational debate on drugs.

References

1. Andrew Macintosh, 20 March 2007. Sensationalism no way to fight drug addiction. Available online: http://www.theage.com.au/news/opinion/sensationalism-no-wayto-fight-drug-addiction/2007/03/19/1174152967041.html
2. Parliamentary Joint Committee on The Australian Crime Commission (February 2007) Inquiry into the manufacture, importation and use of amphetamines and other synthetic drugs (AOSD) in Australia. Available online: http://www.aph.gov.au/senate/committee/acc_ctte/aosd/report/report.pdf

INCB [International Narcotics Control Board] �CLOSED TO REASON�

The Canadian HIV/AIDS Legal Network and the International Harm Reduction Development Program, joined by former United Nations Special Envoy for HIV/AIDS in Africa, Stephen Lewis, held a press conference in March this year to release �Closed to Reason: The International Narcotics Control Board and HIV/AIDS�. The new report details the ways in which the INCB, funded and staffed by the UN, has blocked effective HIV prevention for injecting drug users. The document focuses on errors of fact and omissions in International Narcotics Control Board (INCB) publications and statements, the ways in which the Board has ignored expert legal counsel and scientific evidence, and calls for greater accountability and transparency.
The key finding of the report was that the role of drug policy has been transformed since the era in which the International Narcotics Control Board was founded. It concludes that the Board has become an obstacle to effective programs to prevent and treat HIV and chemical dependence. The authors found that INCB annual reports are rife with omissions and misrepresentations and lack both scientific documentation and justification for legal opinions. They criticise the reports for praising governments that violate human rights, such as Thailand and China.
�Closed to Reason� recommends improved accountability for the INCB and calls for the World Health Organization, the UN Economic and Social Council and UN member states to ensure that the Board includes persons with expertise in HIV/AIDS policy and international law. For the full report in English, please visit: http://www.aidslaw.ca/drugpolicy or http://www.soros.org/harm-reduction

ADDICTED TO TANNING?

The website Medical News Today reports that despite repeated health warnings about the dangers of tanning from sunlight and artificial light sources, there are still those whose mantra �bronzed is beautiful� remains unshaken [1].
<snip>

Reference:

Wood E, Tyndall MW, Zhang R, Montaner JSG, Kerr T. Rate of detoxification service use and its impact among a cohort of supervised injecting facility users. Addiction 2007 102;6:916-9

Data Do Not Support Buprenorphine as a First-Line Treatment for Addiction

Byrne A, Wodak A. Data Do Not Support Buprenorphine as a First-Line Treatment for Addiction. American Journal of Psychiatry 2007 164;11:1757

Letters to the Editor

American Journal of Psychiatry 164:11, November 2007 ajp.psychiatryonline.org 1757 �Data Do Not Support Buprenorphine as a First-Line Treatment for Addiction�

TO THE EDITOR: In the May 2007 issue of the Journal, Johan Kakko, M.D., et al. reported on an excellent randomized controlled trial of �stepped� buprenorphine versus methadone therapy for heroin dependence (1). However, nearly two thirds (65%) of the subjects were transferred to methadone because of continuing illicit drug consumption or cravings. Therefore, this study suggests that methadone should be the drug of first choice for maintenance treatment, and buprenorphine should be reserved for patients who do not respond well to methadone.

Most trials to date have reported that methadone provides superior retention (2). Methadone is also less expensive and easier and faster to administer than buprenorphine and is accepted as a safe treatment during pregnancy.

Dr. Kakko et al. reported a nonsignificant difference in their primary outcome of 6-month treatment retention, with 77% for buprenorphine and 79% for methadone. Such high retention is unusual for trials of this kind. In addition, the high buprenorphine retention may have been partly achieved by a more rapid dose escalation and a higher mean dose (29 mg/day) than usual.

Before the findings of Dr. Kakko et al. are accepted, there should be confirmation of the �noninferiority� of a standardized buprenorphine regimen in a community rather than clinic setting.

Methadone is more toxic than buprenorphine. This finding may not have been apparent in the study conducted by Dr. Kakko et al., since most of their patients ultimately received methadone. In some jurisdictions, buprenorphine is already the most frequently prescribed maintenance therapy for opioid addiction. It is undoubtedly an excellent second-line treatment.

Another important finding in this study was the average dose of 29 mg/day, which is more than double the average in most other studies and almost the manufacturer�s maximum recommendation of 32 mg/day. Such a large dose often takes more than 15 minutes to administer. Dr. Kakko et al. speculated that the inclusion of naloxone (not naltrexone as stated in the editorial accompanying the article) in the combination product may have contributed to the need for such an unusually high dose. Other studies have reported higher doses required for the buprenorphine-naloxone combination (3). However, we are not aware of any rigorous �equivalence� studies comparing buprenorphine with the combination product.

The recommendation by Dr. Kakko et al. that buprenorphine should be considered as the first-line medication, despite 65% of patients being transferred to methadone, is difficult to accept. While industry support is often integral to the development of new intervention strategies, it has also been shown that studies funded by the pharmaceutical industry have a greater likelihood of reporting favorable conclusions (4).

References

1. Kakko J, Gr�nbladh L, Svanborg KD, von Wachenfeldt J, R�ck C, Rawlings B, Nilsson L-H, Heilig M: A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial. Am J Psychiatry 2007; 164:797�803

2. Mattick RP, Kimber J, Breen C, Davoli M: Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. The Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD002207

3. Bell J, Byron G, Gibson A, Morris: A pilot study of buprenorphine-naloxone combination tablet (Suboxone) in treatment of opioid dependence. Drug Alcohol Rev 2004; 23:311�318

4. J�rgensen AW, Hilden J, G�tzsche PC: Cochrane reviews compared with industry supported meta-analyses and other metaanalyses of the same drugs: systematic review. BMJ 2006; 333:782. Epub 2006 Oct 6

ANDREW BYRNE, M.D. Redfern, NSW, Australia ALEX WODAK, M.D.

Darlinghurst, NSW, Australia

Dr. Byrne owns and runs a private clinic that dispenses methadone, buprenorphine, and other drug treatment. Dr. Wodak is the director of a public clinic (free to patients and government funded) that dispenses both methadone and buprenorphine.

This letter (doi: 10.1176/appi.ajp.2007.07071058) was accepted for publication in July 2007.

Dr. Heilig Replies

TO THE EDITOR: Buprenorphine and methadone are both effective treatments for heroin dependence (1). Counting studies on these medications is obviously not a valid method for comparing their efficacy. For retention in treatment, a metaanalysis yielded only a tendency-level advantage for methadone in high-dose studies (relative risk=0.79; 95% confidence interval [CI]=0.62�1.01) (1). In flexible-dose studies, the relative risk was similar, but reached significance (relative risk=0.82; 95% CI=0.69�0.96). For drug use and criminality, the two treatments were reported to be equivalent. Thus, methadone provides a slight advantage over buprenorphine for retention in treatment, and the two medications are equivalent on other relevant outcomes.

Methadone treatment is essential, but also has distinct limitations. As pointed out by Drs. Byrne and Wodak, methadone is �more toxic,� i.e., methadone has sufficient mu-opioid receptor activity to induce lethal respiratory suppression, whereas buprenorphine, a partial agonist, does not. Safety itself aside, the monitoring necessitated by methadone use somewhat detracts focus away from building a therapeutic alliance, which offsets the cost advantage of the medication.

Given the complementary profiles of the two medications, pitching one against the other is not meaningful. The field needs rational ways of using both. In this context, we are unaware of any other therapeutic area in which a safer, albeit somewhat less effective medication, would be reserved for second-line treatment. Optimal balance between efficacy and safety is typically achieved by doing exactly the opposite. For example, few would consider using chloramphenicol for an infection before trying penicillin.

But what if stepping up treatment as needed rather than giving everyone methadone right away led to losing more patients overall? That would indeed mean that the safety gains must be carefully weighed against efficacy losses, an exceedingly difficult tradeoff. Our study was designed to assess whether this is a concern and clearly showed that it is not. Nothing is lost by first trying the safer medication.

In that perspective, the exact proportion of patients who ultimately transfer to methadone is irrelevant. But let us be correct. In our study, among 48 subjects randomly assigned to stepped treatment, 37 remained. Of those, 20 transferred to methadone. That is 54%, which is what we reported. The 65% given by Drs. Byrne and Wodak is a misrepresentation of our data.

In summary, excellent outcomes can be achieved by starting every heroin-dependent patient with buprenorphine and progressing to methadone only if needed. These outcomes are as good as those achieved with the best possible methadone treatment. Among unselected individuals addicted to heroin who are retained in treatment, close to one-half do well without progressing to methadone. Each of these individuals represents a safety gain worth capturing.

Finally, our study disclosed an unrestricted research grant from industry that accounted for approximately 25% of the budget. The remaining funding came from the Swedish Government and Stockholm County. It is unclear how this could invalidate our results. The reference cited (2) by Drs. Byrne and Wodak in support of this notion deals with meta-analyses, which our study clearly is not.

References

1. Mattick RP, Kimber J, Breen C, Davoli M: Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2003;2: CD002207

2. J�rgensen AW, Hilden J, G�tzsche PC: Cochrane reviews compared with industry supported meta-analyses and other metaanalyses of the same drugs: systematic review. BMJ 2006; 333:782 MARKUS HEILIG, M.D., PH.D.

Bethesda, Md. Stockholm, Sweden

Dr. Heilig�s disclosures accompany the original article. [CME Disclosure: Dr. Heilig and Ms. Svanborg received research and travel grants from Schering-Plough. Dr. Nilsson has consulted for Merck. Dr. Kakko has received honoraria from Schering-Plough Estonia, Schering-Plough Sweden, and Reckitt Benckiser Australia. The other authors report no competing interests.]

APA policy requires disclosure by CME

This letter (doi: 10.1176/appi.ajp.2007.07071058r) was accepted for publication in July 2007.

Harm reduction, hepatitis C and opioid pharmacotherapy: an opportunity for integrated hepatitis C virus-specific harm reduction

Drug and Alcohol Review 2007 26;4:437-43

Hallinan R, Byrne A, Dore GJ. Harm reduction, hepatitis C and opioid pharmacotherapy: an opportunity for integrated hepatitis C virus-specific harm reduction.

The Byrne Surgery. Redfern, NSW, Australia.

While harm reduction advocates, policy makers and practitioners have a right to be proud of the impact of interventions such as needle and syringe programmes on HIV risk, we can be less sanguine about the ongoing high levels of HCV transmission among injecting drug users (IDUs) and the expanding burden of hepatitis C virus (HCV)-related liver disease. In this Harm Reduction Digest Drs Byrne and Hallinan from the Redfern Clinic and Dr Dore from the National Centre in HIV Epidemiology and Clinical Research offer a model of integrated HCV prevention and treatment services within the setting of opioid pharmacotherapy.

In their experience, this common-sense approach provides an opportunity to reduce the burden of HCV and improve overall patient management. They believe that the key elements of a HCV-specific harm reduction model include: regular HCV testing; clinical assessment and determination of need for HCV treatment referral; use of broader HCV treatment inclusion criteria; and flexibility in opioid pharmacotherapy dosing. In an environment when our macro harm reduction interventions seem to have, at best, modest impact on HCV transmission, good clinical practice may be our most effective strategy against the HCV epidemic.

This paper provides some practical suggestions as to how this can be done.

Simon Lenton Editor, Harm Reduction Digest.

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

22 May 2007

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.

Buprenorphine maintenance works a treat but detox is a disaster in unselected subjects.

Time-limited buprenorphine replacement therapy for opioid dependence: 2-year follow-up outcomes in relation to programme completion and current agonist therapy status. Kornor H, Waal H, Sandvik L. Drug Alcohol Review 2007 26;2:135-142

Using buprenorphine short-term taper to facilitate early treatment engagement. Brigham GS, Amass L, Winhusen T, Harrer JM, Pelt A. Journal of Substance Abuse Treatment 2007 32;4:349-356

Dear Colleagues,

Kornor and colleagues report a 2 year follow-up of 75 patients entering supervised daily buprenorphine reduction treatment for heroin addiction. An original proposed 9 month reduction to abstinence program was extended to 10 months for compassionate reasons. Even so, only 9 (12%) had achieved and maintained abstinence at 2 years by self-report. Two were lost to follow-up and 5 (7%) died, 3 during the withdrawal phase. Half the total (37) had rejoined maintenance treatments at follow-up.

These authors imply that their research is aimed at countering restrictive policies on maintenance treatment. Norway normally only allows limited buprenorphine, in reduction courses to injectors over 24 years of age, at 3 months maximum per episode. While methadone is available for severely dependent subjects, apparently only a small proportion of the addicted population receive it. The authors conclude that continued treatment may have prevented some of the 5 deaths (3 overdoses, one suicide, one car accident). Based on the high rates of relapse following detoxification, Kornor and colleagues question the ethics of repeating this sort of reduction study in the future. Some critics (eg. Gossop) point to the limited outcomes from maintenance therapy, yet they tend to quote results of treatment given far short of accepted medical guidelines where less than optimal result are predictable.

Brigham, Amass and colleagues report on their first 64 buprenorphine “detox” patients compared retrospectively with two other groups given other treatments, including clonidine, during 2003/4. Their ‘detox’ group took a mean daily buprenorphine dose of 22mg over an average 14 days in ‘treatment’ and 80% were reported to take follow-up treatment. This compared with around 30% for the other groups given non-opioid medications.

This curious ‘study’ has limited meaning beyond indicating that giving ineffective treatment (clonidine assisted detoxification) makes patients unlikely to return for more treatment, which is hardly surprising.

These authors recognise the shortcomings of brief courses of opioids in describing “the critical need for treatment continuation following detoxification”. Their study protocol, however, rather than the stated detoxification, it was rather a ‘re-toxification’ with high doses of buprenorphine, even beyond the usual levels used for opioid maintenance. Thus by definition, their patients did not commence detoxification until after they left treatment. While reduction courses and formal detox should be available promptly to all, maintenance opioids should also be available as a ‘safety net’ where reductions fail to achieve patients’ original goal of abstinence.

The concept of arbitrary time-limited dose reductions goes against the very definition of addiction involving compulsive drug use with a certain degree of loss of control. Some will regain this control, but others will not. Despite a known higher mortality, apparently well-meaning folk continue to propose compulsory detoxification as a valid strategy. They either don’t consider that addiction exists, and/or that the consequent deaths in this group are unimportant. To do a comparable study of medication reduction using subjects with diabetes, depression or asthma would be unthinkable.

Since I have been critical of reduction courses and of using buprenorphine ‘first line’ in the past, I remain hard put to determine a rational strategy for opioid maintenance. As with other areas of therapeutics we are faced with decisions: why do we choose penicillin in place of erythromycin or aspirin against other effective analgesics? It is a combination of known efficacy of available treatments and the particular patient’s individual situation. Most often, in my experience, patients have tried methadone and/or buprenorphine so this can be some guide. The issue of pregnancy or heavy street drug use might sway one towards methadone but previous difficulties with methadone might sway one towards buprenorphine, despite its slightly lower efficacy.

So the great Dr Osler’s advice pertains: listen carefully and your patient will often tell you the diagnosis … and further, many will also tell you the treatment required.

Comments by Andrew Byrne ..

The pros and cons of pharmacy only opioid treatment from Melbourne researchers - coal face views

Drug Alc Review 2007; 26;2:143-152

Nielsen S, Dietze P, Dunlop A, Muhleisen P, Lee N, Taylor D. Buprenorphine supply by community pharmacists in Victoria, Australia: perceptions, experiences and key issues identified.

Dear Colleagues,

This large study examined pharmacists� impressions of prescribed maintenance opiates for addiction treatment in a large postal survey covering 75% of the treatment field in Victoria, Australia, relating to the treatment of about 7500 patients. It is probably the largest such survey in the world literature and had an enviable response rate with the diligence of the researchers using preliminary phone contacts and careful follow up. It may have been beneficial to have had further demographics, average dose levels, numbers of take-home doses (if any), swaps between methadone and buprenorphine, etcetera.

Both methadone and buprenorphine were available in 90% of the pharmacies involved in dependency treatment. The average had been involved for 7 years, treating a median of 16 patients each (range 1-150). Two thirds were metropolitan, one third rural or regional.

Regrettably, but consistent with other Victorian reports (eg. IDRS), the rates of reported diversion of supervised buprenorphine tablets were very high. Overall there were 33 episodes of suspected or confirmed diversion per month for every 100 patients treated. This occurred despite 82% of pharmacies crushing all doses before administration.

Sixty percent of all detected and conceded diversion episodes were stated to be for later consumption by the patient. Twenty percent said that it was to inject.

There were over 100 negative comments by pharmacists, more than half concerning diversion and administration problems. There were less than 20 positive comments from the 287 pharmacies surveyed. Most disappointingly, twelve pharmacists said that they would no longer accept buprenorphine patients due to the difficulties.

The authors speculate about reasons for the high rates of non-compliance. However, they do not question the nature and quality of the treatment being given, nor why the rates would be so different from other Australian states.

Dose levels may have been inadequate for some patients. Access to methadone, the only alternative medication, may have been limited or even discouraged. Take-away doses were very limited at the time of the study for both medications.

It is possible that some of the frustration reported by pharmacists was due to the practice of second daily (double) dosing which was strongly promoted in Victoria. Equally, universal crushing of tablets is time consuming and implies a lack of trust with patients.

Another problem with treatment in Victoria is that few if any dispensaries open early enough for labouring work hours. Hence, holding over some medication for the following day may be a temptation to diversion for those who need their dose before work.

The authors� defense of pharmacy-only treatment runs contrary to their own negative findings in this study. The authors do not make a case against a choice of alternatives such as public and private clinics, hospital, doctor�s surgery, mobile van dispensaries and jail-based treatment services. No single avenue of treatment is likely to suit all patient needs.

Hence the substantial black market reported from Victoria (and elsewhere) may well be due to a community need making a ready and willing market, possibly related to a lack of provision of accessible and appropriate services. The latter is not unique to Victoria, of course, and few jurisdictions to date have fully satisfied the need for opiate treatment services.

These authors are to be congratulated for exposing many major problems with the delivery of buprenorphine in Victoria (diversion, injecting, costs, expulsions, frustrations of health workers, etc). Further work must be done to determine why buprenorphine has apparently been so successful elsewhere as an alternative for those opiate dependent subjects who find methadone unsatisfactory.

In the meantime, it is essential that we all try to bring our own practices closer to the evidence base or �best practice�. There should be good access to a range of service delivery methods, including dedicated clinics; primary care community services for stable patients; no prejudice against methadone; no undue emphasis on 2nd daily dosing and importantly, flexible take-away dose availability (since diversion of a take-away dose is unquestionably safer that diversion of buprenorphine spat out of a patient�s mouth). Also, we should not forget adequate psychosocial supports and choice of treatment.

Comments by Andrew Byrne ..

Randomised Swedish study shows buprenorphine suits 35% versus methadone at 80%

American Journal of Psychiatry 2007 164;5:797-803

A Stepped Care Strategy Using Buprenorphine and Methadone Versus Conventional Methadone Maintenance in Heroin Dependence: A Randomized Controlled Trial. Kakko J, Gr�nbladh L, Svanborg KD, von Wachenfeldt J, R�ck C, Rawlings B, Nilsson L-H, Heilig M.

This prominent Swedish group may have done the field another service without realising it. A previous buprenorphine trial by Kakko et al. (Lancet 2003) had a placebo group with so many deaths (25% within a year) that they unintentionally demonstrated the life saving benefits of buprenorphine treatment (for the first time to my knowledge). They also showed that, at least in the Swedish environment with restricted access to alternative maintenance treatments, even second line treatment can yield a high retention rate of 75% at one year.

In the present study, half of 96 addicted subjects received standard methadone treatment (mean dose 111mg daily) while the rest received buprenorphine with transfer to methadone if needed. The latter occurred according to defined criteria of drug use or cravings, but only after a buprenorphine dose escalation to 32mg daily if this was tolerated. Intensive psychosocial support was also provided. Treatment was supervised daily in the first month when the trial was still double-blinded, in what these authors themselves describe as the �sensitive initial month of treatment�. After documented stability, there was graduation to twice and even once weekly supervised medication with the remainder as �take-away� or dispensed doses, consistent with good practice (see Rhoades 1998).

The final mean dose of buprenorphine was 29mg daily (�5). Consistent with previous research, only 35% of buprenorphine patients remained on the treatment (42% transferred to methadone while 21% dropped out, most notably in the first 3 weeks).

The authors claim that retention rates in the two groups were �virtually identical� (77% bup, 79% meth), yet their decay graph clearly shows an excess of buprenorphine drop outs in the first three weeks of treatment, which is consistent with the reported experience of others. There were only one or two early drop outs in the methadone group yet in those randomised to start with buprenorphine, six or more subjects appear to have departed the trial in this period. Methadone had about the same number of people leaving treatment overall but they did so at a more constant rate over the 6 months of the trial. The high retention rates are probably due to both the high quality methadone treatment offered and lack of alternative sources of maintenance treatment in Sweden.

Both groups had approximately 80% clear urine tests for opiates, also consistent with the adequacy of doses and high level of psychosocial treatment provided these subjects.

Despite these unsurprising findings, the authors write in the article�s abstract: �strategies using buprenorphine as a first line treatment should be considered�. This is changed, without additional explanation or references, to a much stronger conclusion in the text that buprenorphine �should generally be used as the first-line treatment in heroin dependence, with provisions for rapid progression to methadone when needed�. It seems bizarre to recommend a drug with a known failure rate of over 60%, especially when there was an acceptable, cheaper and more effective alternative. In addition, methadone is considered the drug of choice in pregnancy.

We are told that the combination buprenorphine/naloxone drug was chosen partly because it has been approved in the United States. From a �pure science� point of view, this clouds the issue since most research is on the pure product with very little on the combination product. The authors speculate that the addition of naloxone might have caused the high average dose of buprenorphine at 29mg daily (�5mg). The reference cited supporting dose equivalence (Johnson RE 2000) reports no such comparison from my reading of the original paper. The finding of high doses required is consistent with Bell et al 2004 (which is NOT cited by these authors, despite being the only clinical comparison to date, so far as I know). In this, patients needed approximately 50% more buprenorphine when transferred from pure buprenorphine to the combination product. They detail the low primary toxicity of buprenorphine yet they ignore some major problems reported with buprenorphine treatment (deaths in France, diversion in Victoria, injection, low efficacy, costs). They also fail to remind readers that most methadone overdose has occurred from its use outside the supervised clinic setting, meaning pain management prescriptions, break-ins, etc. See Ballesteros where only 4% of methadone overdose deaths in North Carolina in a five year period occurred in registered maintenance treatment recipients.

We are informed that this trial was partly funded by Schering-Plough Sweden. Four of the authors have received funds from drug companies. Three of these were from the manufacturer of buprenorphine and one author received funds from this source in three separate countries (Estonia, Sweden and Australia).

These authors quote the term �non-inferiority� four times in their article regarding their customised �stepped care strategy� based on retention rates and toxicology. In this comparison, however, they do not take into account several other important factors including dose, costs and patient satisfaction. They state that �no patients commented on transitioning� (sic) from buprenorphine/naloxone to methadone. Yet such patients must have been faring poorly on buprenorphine and must have had some views on finally being prescribed the more effective drug. Some might also possibly have had some views at being given the less effective drug initially in the trial, despite the consent process. Have any of these �transitioning� patients been asked to comment on the authors� suggestion relating to first line buprenorphine, I wonder? One may worry that some needle sharing or overdose might have occurred in the interim period, not to mention the 12.5% who appear to have dropped out altogether in this early period from the �stepped care� group. We are not informed if any died although in Sweden such information would probably be easily available, as in previous reports.

It would also be instructive (and equitable) to know how many of the methadone patients may have clinically indicated a transfer to buprenorphine. We find the rate is between 10 and 30% in our own practice. This may well have applied to some of the drop-outs and even to some of those retained in the treatment, who may have preferred buprenorphine for a variety of reasons. Such a matched or parallel protocol might have increased methadone retention to 90% or higher. Hence this is another flaw in the current trial and another reason to question the authors� enthusiastic endorsement of the buprenorphine combination as a first line drug in dependency treatment.

Note that an editorial by Kathleen Brady in the same issue points out several more disadvantages of the current study. Few medical practices would have the resources to give such intensive psychosocial support as occurred here. Brady uses the incorrect term �naltrexone� rather than �naloxone� no less than ten times. She also states that if injected, the �naltrexone will precipitate withdrawal�. Assuming that she is referring to naloxone, this is not the case for most buprenorphine maintained patients and only for a proportion of others with current habits on pure opiate agonists (eg. methadone, heroin or morphine). She also points out that the �stepped care� can only work if there is closely supervised treatment such as in existing methadone clinics. This would defeat the supposed purpose of office based treatment which has not been extensively tested against clinic based treatment to my knowledge. I believe that the authors are also mistaken in their choice of the term �stepped care�. This would refer to additional medication or other treatment, based on pre-existing criteria. This trial, however, uses a �safety net� or �rescue� protocol and not a �stepped care� approach in my view.

Comments by Andrew Byrne ..

References:

Ballesteros MF, Budnitz DS, Sanford CP, Gilchrist J, Agyekum GA, Butts J. Increase in Deaths Due to Methadone in North Carolina. JAMA 2003 290:40

Bell J, Byron G, Gibson A, Morris A. A pilot study of buprenorphine-naloxone combination tablet (Suboxone�) in treatment of opioid dependence. Drug Alcohol Rev (2004) 23;3:311-318

Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-associated relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. (2003) Lancet 361:662-668

Nielsen S, Dietze P, Dunlop A, Muhleisen P, Lee N, Taylor D. Buprenorphine supply by community pharmacists in Victoria, Australia: perceptions, experiences and key issues identified. Drug Alc Review 2007 26;2:143-152

Rhoades HM, Creson D, Elk R, Schmitz J, Grabowski J. Retention, HIV Risk, and Illicit Drug Use during Treatment: Methadone Dose and Visit Frequency. 1998 Am J Public Health 88:34-39