1. Substance Use Disorders
Dr Hani Zakri
ST3 in Psychiatry
Drug Addiction: A Complex Illness
Drug addiction is a complex illness. The path to drug addiction begins with the act of taking drugs. Over time, a person’s ability to choose not to take drugs is compromised. This in large part is a result of the effects of prolonged drug use on brain functioning, and thus on behavior. Addiction, therefore, is characterized by compulsive, drug craving, seeking, and use that persists even in the face of negative consequences. 1

3. “.”
“Here's to alcohol: the cause of, and solution to, all of life's problems.”

4. Substance use disorders Summary
Classification
Aetiology
Neurobiology
Alcohol withdrawal
Delirium Tremens
Wernicke Korsakoff Syndrome
Opiate Dependence
Management of opiate withdrawal
Treatment approaches for substance use problems
These are some of the aspects I will be touching upon today during the course of the next one hour.

5. A SIMPLE CLASSIFICATION
Stimulants; wake you up, speed you up and give you energy e.g. amphetamine, cocaine and Ecstasy
Depressants; make you calm and drowsy e.g. opioids, benzodiazepines,volatile substances and cannabis
Hallucinogens; change your perception, by distorting what you see and hear e.g. LSD and magic mushrooms
A very simple classification of drugs can be based on their effect. So that would be as stimulants, depressants and hallucinogens

6. Spectrum of substance use
Recreational Use
Acute Intoxication
Harmful Use
Dependence syndrome
Sustance use can exist anywhere along this broad spectrum, from recreational use which can include your average trip to the pub to a full fledged dependence syndrome

7. Acute intoxication
Transient condition following use of alcohol or drugs, closely related to dose and following which recovery is usually complete.
I’m sure a lot of you have been in this position before, so I don’t really need to elaborate further on this. The key here is that recovery is usuallly complete.

8. Harmful Substance Use A pattern of substance use that causes
damage to physical health, mental health
or social circumstances.
Ingestion of excessive amounts
“Idiosyncratic” Reactions e.g. XTC
Accidental Overdose e.g. heroin
Method of Administration e.g. IV use
Police involvement, Work affected etc.
In addition to these examples whats also important is to remember that harm need not be restricted only to physical health. Mental health problems secondary to drug and alcohol use such as drug induce psychosis shall also come under this.

9. Wake up Question?
Mr Smith used to drink at various places , having various drinks. Now he drinks just only at home sticking to vodka?
Salience
Narrow repertoire
Loss of control
Relief drinking
Tolerance

10. Dependence Syndrome: 3 or more of the following in the past year…..
Compulsion and Cravings
Physiological withdrawal state on cessation, relief use
Tolerance
Difficulty controlling onset, termination, levels of use
Salience/Primacy – neglect of alternative pleasures
Persistent use despite overt harm
(reinstatement, narrowing of repertoire)
The next step in the progression of the disorder after harmful use. The 5 C’s as well as other features such as reinstatement after a period of abstinence and narrowing of repertoire.

11. Wake up Question?
Which one of the following is not criterion for dependence according to DSM-IV?
Tolerance
Withdrawal
Compulsion to drink
Loss of social activities
Continued intake

12. AETIOLOGY

13. “Biopsychosocial”
I’m sure this is a term u have all heard before, few other disorders capture the essence of this better than susbtance use disorders

14. Theories & Genes Social learning model: maladaptive behaviour
Disease model : loss of control, reduce self blame
4 alcohol dehydrogenase : mild protection
12 aldehyde dehydrogenase : 12% oriental ; significant protection.
40% had family Hx
4 fold increase risk of alcoholism

15. Disposition to drug/alcohol use
Individual
Social
Factors influencing an individuals substance use
Early influences
Genetic predisposition- explains 60% risk in alcoholism, 4x↑in 1st degree rels, MZ/DZ concordance = 2/1
Key learning experiences
Adopted children x ↑4 risk
Personality factors- socially phobic, anxious, impulsive, risk taking v cautious
Early influences
Peer group influences
Family, parental substance use
Cultural factors
Immediate factors
Demographic factors, Occupation
Social pressures, Peers, Religious beliefs
Availability, Price, Advertising
Immediate factors
Mood states
Withdrawal states
Disposition to drug/alcohol use
Approach
Avoidance
Quite a crowded slide. It attempts to look at the factors which influence an individuals susceptibility to use substances as well as the factors which influence his behaviour once he begins to use them
Drug/alcohol Use
Aversive consequences
Toxic effects
Illness
Psychosocial dysfunction
Reinforcing consequences
Mood enhancement
Psychosocial facilitation
Relief of withdrawals, neuroadaptation

16. Wake up Question?
Chris and ken are class mate. Chris’s dad is alcoholic. How many times is Chris more likely to have problems with alcohol?
2-3 times
4-10 times
10-20 times
50 times
100 times

17. NEUROBIOLOGY
I’ll speak a bit about the neurobiology behind substance use.

18. The reward pathway Slide 11: The reward pathway
Tell your audience that this is a view of the brain cut down the middle. An important part of the reward pathway is shown and the major structures are highlighted: the ventral tegmental area (VTA), the nucleus accumbens and the prefrontal cortex. The VTA is connected to both the nucleus accumbens and the prefrontal cortex via this pathway and it sends information to these structures via its neurons. The neurons of the VTA contain the neurotransmitter dopamine which is released in the nucleus accumbens and in the prefrontal cortex (point to each of these structures). Reiterate that this pathway is activated by a rewarding stimulus. [Note: the pathway shown here is not the only pathway activated by rewards, other structures are involved too, but only this part of the pathway is shown for simplicity.] 18

19. Reward Pathway activated by.
Natural Rewards…… Food
Water
Sex
Nurturing
Exercise ……
Chemical Rewards
Drugs and alcohol
Coffee
Nicotine…….
As addiction develops natural rewards becomes less effective
Normally the reward pathway is activated by natural rewards which act as positive reinforcers. But drugs of abuse produce far greater effects on the pathway than natural rewards. Therefore over time the brain directs its normal drives away from natural rewards towards the drugs. In severe addiction as occurs with the more powerful drugs such as heroin all natural drives may be subsumed to the need for the drug and addict may ignore his self care, food, work etc

20. ALCOHOL

21. Epidemiology
Alcohol consumption ↑, costs Scotland > £1 billion/year
M/F ratio 2/1,trend towards ↑drinking in young women while men 20-24
27% men,14% women in Scotland drink in excess of the government recommended limits (Scottish Health Survey 2003)
33,000 premature deaths /yr in Eng, Wales
One of the biggest public health problems. Costs scottish economy more than one billion each year. Also no matter what field of medicine u specialise in there is no escaping from dealing with alcohol related morbidity.

22. Epidemiology 1 in 5 attending GPs 1 in 6 attending A&E
1 IN 16 hospital admission
Vulnerable populations... Homeless (1/3), prisoners
80% suicides, 80% deaths by fire, 50% homicides
40% RTA’ s, 30% fatal RTA’ s, 15% deaths by drowning

23. Screening tools CAGE: sensitivity 62%
AUDIT (Alcohol use disorder s identification test ): sensitivity 83%
MAST (MICHIGAN alcohol screening test)

24. CAGE Have you ever felt you should Cut down on your drinking?
Have people Annoyed you by criticizing your drinking?
Have you ever felt bad or Guilty about your drinking?
Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover (Eye opener)?
4 quick questions, can be easily fit into a consultation. Important to ask them before taking an alcohol history.

25. Recognition and detection of alcohol problems
Amount in units
Pattern of drinking
Time of first drink, Early morning withdrawals
Compulsion, craving, tolerance, salience
CAGE > 2 positive ? Alcohol dependent
GGT (80% sensitivity 80% specificity, detects 1/3)
MCV(50% sensitivity, 90% specificity, raised in 60%)
CAGE+MCV+GGT detects 75%
First step is obviously to recognise and identify the problem, be it in general practice or in the OPD or in the hospital wards. Take a good history.

26. Sensible Drinking Low risk: Men < 21 units/week
Women < 14 units/week
Harmful Drinking: Men >50 units/week
Women >35 units/week
2 alcohol free days per week
No more than 8 units in one sitting
RCPsych, RCGP, RCP

27. Units Unit = vol of alcohol (mls) x ABV (%) 1000
1 unit = 8 g alcohol= 1 std measure
spirits, ½ pint beer
ABV= alcohol by volume

28. Wake up Question?
The amount of alcohol in two pints (568mls) of beer at 4% ABV is:
7 U
10 U
2 U
5 U
4.5 U

29. Biopsychosocial effects of alcohol
Physical - Dyspepsia, HBP, Gout, Psoriasis, Falls, Trauma, Withdrawal syndrome, Cirrhosis, Cardiomyopathy, Neuropathy, Seizures, Death
Mental - Depression, Anxiety, ARBD, Psychosis (Hallucinosis), Blackouts
Social - Marital diffs, absenteeism, debt, drink driving, legal problems, drifting, unemployment, Homelessness, Isolation, deprivation.
So what does alcohol do to u? well a whole bunch of not so nice things

30. Neuropharmacological Effects
Mechanism not well understood
CNS Depressant
Enhances inhibitory neurotransmission at GABA- A receptors
Reduces Excitatory transmission at NMDA Glutamate Receptors

31. Alcohol withdrawal Often missed clinically!
Suspect if anxious, restless, irritable, alcohol on breath, excessive capillarisation on facial skin/conjunctivae,↑GGT, MCV, AST/ALT ratio >2
Majority - 85% require no detox… advice, support will suffice as mild, self limiting
< 5% develop Delirium Tremens (DT’s)
A few will need inpatient detoxification
( DT’S, Epilepsy, no social support)
Most detoxs’ done as day patient

32. Wake up Question?
The mortality rate for person treated for alcohol withdrawal : 1%
20%
30%
40%
50%

33. Alcohol Withdrawal
> 10 units/day will likely experience some withdrawal
Spectrum of severity
Usually within 24 hours after last drink
Lasts 5-7 days
*Tremor*Nausea*Sweating* Headache, ↑HR, ↑ BP *Dysphoria - depression, anxiety, sleep disturbance, sensitivity to sound, hallucinations, seizures

34. Wake up Question?
What is the typical time period in which withdrawal Sx appear?
2 weeks
2-3 days
2 months
5 days

35. Management Diagnose it! Quiet, well lit room with familiar staff
Exclude other co existing pathology
Re hydration
Benzodiazepines… Chlordiazepoxide on reducing scale
Regular review
Parenteral B vitamins ..to prevent Wernicke’s – must be given IV or IM

36. Wake up Question?
Which is the treatment of choice for seizures (SE) in alcohol withdrawal?
Diazepam
Phenytoin
Carbamazepine
Lorazepam
Chlordiazepoxide

37. Complications Uncontrolled withdrawal Delirium Tremens
Withdrawal seizures
Wernicke's encephalopathy
Elderly maybe sensitive to benzodiazepines, cautious monitoring.
Patients with liver disease may be sensitive to benzodiazepines, cautious monitoring.

38. Wake up Question?
Failure to Dx and Tx with thiamine for Wernicke's encephalopathy has mortality rate of : 5%
10%
20%
30%
50%

39. Delirium Tremens Severe withdrawal state – medical emergency
Reduced or stopped drinking hrs
Precipitated by trauma, infection, head Injury
Tremor, sweating, dehydration, fever, ↑HR, ↑temp, HBP, agitation, delirium - fluctuating consciousness, orientation, hallucinations - *visual, fear, paranoia, seizures,, circ.collapse
5-10% mortality treated, 35-40% Untreated
Best treatment is prevention!
Hallucinations: complex and appear very realistic. Pt. described a 5 piece band made up of leprechauns who came out from behind the ecg monitor at night and played for him.

40. Management Early diagnosis Quiet, well lit room with familiar staff
Exclude other co existing pathology
Re hydration
Regular review
Benzodiazepines - may need high doses
Parenteral B vitamins – Wernicke’s
Haloperidol if hallucinating

41. Wake up Question?
Malnourished Patient was due surgery. Developed DTs, no signs of Wernicke's encephalopathy. What is your best strategy for thiamine replacement in this patient ?
Oral thiamine 30 mg TDS
Oral thiamine 50 mg TDS
IV thiamine 250mg TDS
IM thiamine 50mg TDS
Not required

42. Wernicke – Korsakoff syndrome

43. Wernicke – Korsakoff syndrome
Organic brain syndrome induced by deficiency of Vitamin B1 - Thiamine
Wernicke’s encephalopathy - Acute Confusional State, Ataxia, Nystagmus, Tremor Ophthalmoplegia
Korsakoff’s syndrome- long term sequelae. STM impairment, confabulation

44. Wake up Question?
If untreated what percentage Wernicke’s encephalopathy develop Korsakoff’s syndrome? 5%
10%
20%
30%
75%

45. Thiamine Co enzyme in glucose, lipid metabolism
Involved in the production of A A’s, glucose derived neurotransmitters, Myelin
Neurotoxicity occurs when citric acid cycle is impaired and lactate accumulates
Deficiency due to
Reduced intake - alcohol for food, GI upset
Malabsorption - malnutrition, effect of alcohol
Reduced storage - liver damage
Impaired utilisation - liver damage
Glucose load on admission to hospital
(glucose drip! , meal)

46. Wernicke – Korsakoff syndrome
Fallacies –
1.Rare condition -
NO ! actually common and often missed, less than 10% diagnosed before post mortem
2.Classic triad necessary for diagnosis -
NO ! - classic triad only present in 10% of cases, presentation is non-specific, most common feature is confusion
Classical triad of ataxia, opthalmoplegia and confusion

47. Wernicke’s encephalopathy
Potentially life-threatening
Potentially treatable
Clinical diagnosis “non specific presentation”
10% classic triad, 23% ataxia, 29% ophth.
82% confusion - non specific - assoc with W/D, DT’s, ↓ BP, ↓ temp
Can evolve as series of minor sub clinical encephalopathies
(Acute/insidious onset - similar pathology)

48. Wake up Question? The symptom that responds earlier to thiamine is :
Ataxia
Confusion
Opthalmoplegia
Amnesia
Apathy

49. Korsakoff’s syndrome Classically - STM memory impairment
Confabulation (not universal)
Rel.intact intellectual functioning
Not always preceded by Wernicke’s
memory of remote events may also be disturbed, memory often improves
Overlap with alcohol dementia
Personality change, ↓ spontaneity etc.
Charecterized by deficiets in anterograde and retrograde memory, apathy and relative preservation of other intellectual abilities.

50. Prognosis of Korsakoff’s Psychosis
Worse if sudden onset and “pure”
Better with more global cog. Impairment – rewiring?
Better in non alcoholic cases of WKS
Improves with abstinence from alcohol
Victor % Long Term Care
28% slight recovery
25% sig. recovery
21% complete recovery

51. Treatment Prophylaxis - all inpt detox 1 pair iv/im 3-5 days
Treatment pairs iv/im TDS 3 days
If response 1 pair 5 days
no response stop 3 days
Ataxia, polyneuritis, confusion, ↓ memory - continue to treat as long as clinically improving
Dilute, infuse over 30 mins, CPR facilities

52. Wake up Question?
The following are diagnostic features of alcohol dependence except:
compulsion to take alcohol
escalation of amount used
withdrawal syndrome
visual hallucinations.

53. Wake up Question? The following drugs are correctly described:
disulfiram inhibits the breakdown of alcohol
acamprosate is a potent anticonvulsant
naltrexone blocks the effects of endogenous opioids
chlormethiazole is the treatment of choice for medically assisted detoxification.

54. Wake up Question?
The following is NOT cause of raised mean cell volume:
iron deficiency anaemia
Alcohol
pernicious anaemia
pregnancy
heavy smoking.

55. Wake up Question?
All of the following tests usually remain elevated for four weeks or more after an episode of alcohol misuse except?
aspartate amino transferase
white cell count
serum ethanol
gamma glutamyl transferase.

56. DRUGS

57. Epidemiology 1/20 Scottish adults have used drugs in the past month.
1% adults in Glasgow opiate dependent
70% IVDU in Glasgow Hep C positive
Major public health problem. Not just in terms of the direct effects of drug use but also as a result of the knock on effects. So things like hep c and hiv from ivda and increase in crime to fund drug habits

58. Opiate Intoxication ↓Pupils, ↓consciousness, ↓RR, ↓HR, Coma→ Death
Medical emergency
Naloxone iv – but Beware - short acting (45min)!!!
Why?.. Purity of street heroin variable, “greedy”,
Loss of Tolerance after detox,
“Accidental OD’s” esp. if poly drug use
“Re instatement deaths”

59. Biopsychosocial effects of Opiates
Physical - Constipation, loss of appetite, lethargy, accidental OD, Withdrawal syndrome, HIV, Hep C , Weight Loss, DVT’s, abscesses, infections
Mental - mood swings, depression
Social - Family and marital problems, absenteeism, Debts, Lifestyle change- drug seeking, Imprisonment, Homelessness, Isolated, Violence, Prostitution,

60. Wake up Question?
Tolerance does NOT develop to which of the following :
Sedation
Insomnia
Constipation
Miosis

61. Opiate Withdrawal – “flu”
Spectrum of severity
Within 12 hours, peak 72 hours
Pupillary dilatation, Piloerection, Rhinorrhoea, Lacrimation, Sneezing, Nausea, Vomiting, Diarrhoea, Muscle, stomach cramps, Anxiety, Dysphoria, Cravings, ↑HR, HBP
Resolved within a week but some mild symptoms persist longer - sleep, mood

62. Wake up Question?
Which of the following is NOT found in opiate withdrawal ?
Abdominal pain
Dry eyes
Vomiting
Sweating
Dilated pupils

63. Wake up Question? The half life of Methadone in regular user is :
4-6 hours : opioid naive
10-20 hours
24-36 hours
72-90 hours
1 hour

64. Management…… Opiate withdrawal is not an emergency!!!
Take time to consider options, be safe
Don’t be pressurised into prescribing
Options are detox. or substitution, will need worked up for both
Depends on the patient’s wishes and overall situation at the time
No point de-toxing if they wish to continue using, or if they are socially unstable (reinstatement death!)
Counsel carefully.
Incorporate harm reduction advice

65. Management - Detox
Lofexidine detox– alpha 2 agonist , usually as a day patient, rarely as in patient - relieves physical withdrawal symptoms
Supportive care and adjuvant treatment with Buscopan, Paracetamol, Imodium, diazepam
Naltrexone “Blocker” after detox, reduces cravings
Counselling
Psychosocial Help
Warn Re: loss of tolerance and risk of Reinstatement death!!!!!

66. Wake up Question?
What is the equivalent dose of methadone for 0.5 g of street Heroin?
30-40 ml of 1mg/ml mixture

67. Management - Substitution
Confirm opiate dependence by urine and observation of withdrawal
Titrate substitute carefully
Work towards stability and then detox
Methadone
Must be daily supervised dispensing
1/3 leakage to street!
Buprenorphine – sublingual, again supervised
dispensing as risk of leakage: drug of choice in low BP

68. MANAGEMENT PRINCIPLES

69. Matching patients to treatment
No single treatment is appropriate for all
Effective treatment addresses multidisciplinary needs not just drug and alcohol use
Treatment must address medical, psychological, social, family, legal, and vocational problems.
No one size fits all

70. Principles of Treatment
What stage are they at ?
How can I best help this person at this stage?
Would they like help? Are they Motivated?
“Psycho education”
Are they aware of the facts and options?
“Harm Minimisation”
Will they consider reducing intake? Safer use?
“Abstinence”
Do they wish to stop completely?
“Pharmacotherapy ”
Will they consider medication?
“Psychological treatments”

71. What stage are they at? Enter: Harmful use
Exit: Abstinence, moderation
Relapse
Pre- contemplation
Maintenance
Action
Contemplation
“Cycle of Change” Prochaska and DiClementi (1984 )

72. Harm minimisation: Cutting down B vitamins to protect brain (alcohol)
Smoking instead of injecting
Using Needle exchange
Hep B vaccination
Safe Sex advice (Hep B,C,HIV)
Substitution therapy - Methadone
↓alcohol if Hep C positive and opiate dependent
Risks of cocaine, Alcohol – “coca ethylene”

73. Abstinence: Really ready to give it up? Is this the right time?
Good social support?
Need a Detox?
Need Rehabilitation?
Will medication help?- cravings, relapse prevention

74. Detoxification Not always necessary Not always desired
Must be planned, never rush into it
Timing is crucial
Alcohol detox usually as day patient, but some need in patient( fits, DTs, Head injury, isolated)
Opiate detox usually as day patient

75. Psychotherapy Counselling Motivational enhancement therapy
Relapse prevention therapy
CBT
Social skills training
Group therapy
Family therapy
Twelve step programmes - AA, NA
Residential rehabilitation

76. THANK YOU