Concord Dependency Seminar 31 July 2007.
PERSONALITY DISORDERS.
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 http://www.redfernclinic.com/c/2007/08/personality-disorders-supplement.php4).
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 http://www.redfernclinic.com/c/2007/08/personality-disorders-supplement.php4
31 July 2007
Personality disorders (by Dr Glenys Dore) supplementary notes.
Concord Dependency Seminar 31 July 2007.
PERSONALITY DISORDERS
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
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.
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.
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