Psychiatry lecture on addiction

1. Lecture Series
 Alcohol Use Disorders and management
 Community Psychiatry
 Rehabilitation Psychiatry

2. Alcohol
Quiz
1. Alcohol is a central nervous system stimulant leading to
high degree of excitement and garrulousness.
2. Alcohol has been shown to stimulate the release of
dopamine from the ventral tegmental area of the midbrain
3. Alcohol causes damage to most systems in the body
except the musculoskeletal system.
4. Down regulation of Dopamine receptors follows one week
use of large quantities of alcohol.
5. Obsessive compulsive pursuit of alcohol is a typical
symptom of alcohol dependence

3. SUBJECTS
Neurobiological basis of dependence
The mesocorticolimbic system.
The initiation of dependence
Basal ganglia surge of DA....binge.....hijack
Amygdala mediated negative emotions
Hippocampus short term to long term memory learning
Frontal lobe (executive function centre)
..Executive dysfunction
Other neurotransmitters=GABA, Glutamate, Opioid, adrenergic
neurotransmitters (Locus ceruleus)
Evidence based management

4. Alcohol destroys more than the person

5. Atiology of Alcohol Depedence
The Biology of Addiction

7. Neurobiology of addiction
 Three principal regions of the brain influence addictive
behaviours
 Basal ganglia
 Amygdala
 Prefrontal cortex
 All have DOPAMINE pathways from the midbrain (Ventral
Tegmental Area, VTA)
 Mesolimbic (DA projection from VTA to limbic areas)
 Mesocortical (DA projections from VTA to prefrontal)

8. Mesocortical Pathways
Dopaminergic projections
from VTA of the midbrain
Primarily to the prefrontal cortex (PFC).
Involved in cognition, working memory, and decision making
Executive funtions.

9. Mesolimbic Pathways
This a part of complex circuits involving the amygdala,
hippocampus, and the bed nuclei in the basal ganglia.
Projections from ventral tegmental area (VTA) of the
midbrain.
To Limbic area.....Nucleus accumbens/amgdala/hypothalamus
Releases Dopamine when stimulated by pleasurable stimuli
food, sex, drugs etc,
Mediates feelings of pleasure and reward
Overstimulation can lead to euphoria.......craving

10. Other Dopamine Pathways
 Nigrostriatal Dopamine Pathways
 Dopamine projections from substantia nigra to Basal
Ganglia (caudate and putamen)
 Stimulate purposeful movement.
 Dysfunction leads to motor control impairment.
 D2 antagonists ( antipsychotics), block nigrostriatal
pathway and can cause extrapyramidal symptoms.

11. Other Dopamine Pathways
 Tuberoinfundibular Dopamine Pathways
 Dopamine pathways in the hypothalamus
 From the arcuate and periventricular nuclei of the
hypothalamus, to the infundibular area of hypothalamus,
 Dopamine is released into the portal circulation to the
pituitary gland.
 Dopamine inhibits prolactin release.
 Prolactin mediates Sexual satisfaction (countering the
arousal effect of dopamine).
 Blockage of the D2 receptors, (with antipsychotics) prevent
dopamine’s inhibition of prolactin, affecting menstrual
cycles, libido, fertility, galactorrhea.

12. Amygdala
 Situated below the Basal Ganglia
 Involved in Stress Reaction
 Fight and Flight
 Unease, anxiety, irritablity
 Prompts use of drugs to cope
 Alcohol stimulates to increase stress coping reaction

13. Basal Ganglia
 Several groups of neurons at the base of the cerebrum
 2 subgroups of the neurones involved in addictive
behaviour
 Dorsal Striatum
 Ventral Striatum: Nucleus Accumbens (NA)
 Control:
 Movements
 Reward
 Pleasure
 Responsible for the habit of susbtance taking

14. Prefrontal Cortex
the prefrontal cortex (PFC). The PFC is highly involved in
cognition, working memory, and decision making 2. Thus,
when dysfunction within this pathway occurs, individuals
may experience poor concentration and the inability to
make decisions.

15. Drugs of abuse act on Dopaminergic circuitry
Cocaine directly stimulates the VTA
Nicotine, Opiates, Alcohol Indirectly stimulate VTA
The sensitisation of this circuitry makes an individual toward
liking/wanting more of the drug.
Drugs (and the cues associated with the drug) cause
preferential/exponential pleasure value due to the drug's
“hijacking” of dopaminergic circuitry.
Disrupted mesocorticolimbic function (involving the
EXECUTIVE FUNCTIONS) results in impaired inhibitory
control and reward processing, which together manifests as
compulsive drug taking behaviour.

17. Initiation of addiction Binge (Basal Ganglia) Stage
 WITH REPEATED USE OF DRUGS, the drug hijacks the
brain reward system
 Brain Reward Systems depend on
 Dopamine (DA) receptors
 Endogenous Opioids: endophins, dynorphin,
Cannabinoid system
 The Hijack leads to the Nucleus Accubens
producing DA (prefentially and exponentially) in
response to the drug compared to other
preasurable activities.

18. Processes of addiction
 EVERYBODY FEELS PLEASURE...EVERYBODY
 Drugs cause pleasure
 The enjoyment leads to desire to use more drugs
 With motivation to use more drugs
 This is positive reinforcement
 Which leads to repeated use of the drug
 After long period of drug enjoyment, no drug leads to anxiety
 With motivation to use drugs to relieve the anxiety.
 This negative reinforcement
– Relief leads to further Compulsive use entrenching
addiction

19. Experience of addiction
 Many people like AIR TRAVEL.........
 Like many people like alcohol
 IMAGINE WHEN YOUR PLANE IS
HIJACKED!!!!
 LOSS OF CONTROL
 UNPREDICTABLE JOURNEY
 ROLLER-COASTER JOURNEY
 FRUSTRATING JOURNEY
 With repeated ingestion of alcohol...
 Alcohol HIJACKS brain REWARD CIRCUIT
leading to loss of control and roller-coaster,
frustrating and unpredictably alcohol use
journey

20. Practise Question
Alcohol dependence has long been considered
to be a disease of human weakness. With the current
understanding of the biological basis of addiction, discuss
the role of human weakness in development of alcohol
addiction.
Introduction........what do you know about human weakness and alcohol addiction?
Theme 1 The structure of the brain involved in addiction
Theme 2 Neuroscience processes/postulations of addiction initiation and addiction.
Or the "hijack" theory of addiction.
Theme 3 Biopsychosocial model of addiction
Theme 4...The role of prefrontal cortex and disorder of executive functions
Conclusion....Your own perspective. Do you believe the "human weakness" theory or the
neurobiological theory of addiction.

21. Bio-Psycho-Social Model of addiction
CONCLUSION
The nature of addiction is COMPLEX.
Multiple factors interact to influence drug use and
dependence. Different biological, psychological
and social factors may be more or less significant
at different stages of addiction process, from
initiation of use and persistence of use

22. Epidemiology
America
6.2% in general population
18% in recreational users.
UK (Alcohol)
Harmful use
15% of men (more than 35units)
4% of women more than 25 units
IN NIGERIA
Okada riders in Ekiti
14% admit to early morning use of alcohol (Ogundipe et al)

23. Epidemiology of alcohol in Nigeria
Alcohol use disorder Alcohol dependence
Male 3.8 1.0
Female 0.4 <0.1
Both sexes 2.1 0.5
WHO REGION 3.3 1.4
WHO Health Organisation 2014.
12 month prevalence of alcohol use disorders and alcohol dependence 2010

24. Bio-Psycho-Social Aetiology Addiction
Biological Psychological Social
Predisposing Genetic
Family history
Identical twins
reared
apart
Low
endogenous
opioid activity
Personality
Anxiety
Low confidence
Poor assertiveness
Pschodynamic factors
Conditioned learning
Self medicating
amphetamine
Anger control
Peer pressure, to belong
Low level of school
achievement
Being young in one’s cohort
Poor relationship with own family.
Parental drug use
Media influences
Social network
Cultural influences
Religiosity protects
Precipitating/
Initiation
Bingeing
Reward
system
Reinforcement
Negative reinforcement
Positive reinforcement
Company of users
Easy availability
Perpetuating Receptors
Down
regulation of
receptor
mechanisms
Executive
Function
disorer of PFC
Tolerance
Psychological
dependence
Treatment failures
Ignorant treatment approach

25. Management Alcohol Use Disorders
 Pre-detoxification
 Detoxification
 Post-detoxification

26. Pre-detoxification
 Harm reduction

 Readiness to change assessment
 Precontemplation/Comtemplation/Preparation/Action
 Motivational interviewing techniques
 Precontemplation/Contemplation/Preparation/Action
 Preparation for detoxification

27. Pre-detoxification
 Clinical assessment
– Diagnostic category
• CAGE/FAST/AUDIT/
• ASI (Alcohol Severity Index)
• CIWA (>20/67)
– Aetiology of dependence in THIS patient
– History of treatment
– Complications
• Thorough physical examination
• Bloods/ Liver enzymes

28. DETOXIFICATION
Medical management of alcohol withdrawal syndrome.
AW reflect over-activity of the autonomic nervous system.
AW appears 6-24 hours after cessation of alcohol
Symptoms increase into a crescendo and then diminish
Stop in 24-48 hours.
Seizures in 25%
Delirium Tremens occurs in 5-8% in 2-4 days
Characterised by INCREASE IN EVERYTHING.
pulse/BP/Breathing/motor/
Complicated by Co-morbid states

29. Co-morbid states
Assessment must be directed at detecting any-comorbidity
Arrhythmias
Heart failure
Hepatitis
Pancreatitis
Infections (TB)
GI Bleeding
Neuropathies
Dehydration and nutritional deficiencies
Disturbances of eletrolytes

31. Neurochemistry of alcohol withdrawal
GABA = Glutamate balance
GABA excitation causes the clinical symptoms of withdrawal
– autonomic over activity ( tachycardia, tremors, sweating)
– neuropsychiatric complications such as delirium and seizures.
Dopamine
– Involved in alcohol withdrawal states.
– Increase in CNS dopamine levels contribute to the clinical
manifestations of autonomic hyper arousal and hallucinations.
– Repeated episodes of withdrawal and neuroexcitation results
in a lowered seizure threshold predisposing to withdrawal
seizures.

33. Alcohol intoxication
Slurred speech
Dizziness
Excitability
Garrulousness
Unsteady gait
Nystagmus
Poor attention and memory
Hypoglycaemia...seizure......can lead to death
Stupor.......coma
Double vision

34. Alcohol withdrawal syndrome
Dehydration
Depression
Headaches
Tremor
Heightened sensitivity to light/sound
Anxiety
Irritability
Insomnia
Sweating
Seizure in 25% in 25hours after last dose

35. CONTROVERSIES
Pharmacological intervention
which medication?
use of drugs with abuse potential!!
Use of anticonvulsants?
doses: What dose regime?
Setting of treatment
Hospital V Community
Measuring drug effects

36. SIGNS SYMPTOMS
Elevated blood pressure Anxiety
Elevated Pulse...Tachycardia Insomnia
Elevated temperature Illusions
Elevated ......Sweating Hallucinations
Elevated motor ...Tremulousness Paranoid ideas
Elevated pupil.......Dilated pupils Nausea
Elevated arousal Irritability
Disorientation
Grand mal

37. MINOR WITHDRAWAL Starts in 6hours
Lasts up to 48 hours
Tremors, sweating, tachycardia, GI Upset,
Headache, Anxiety, Clear sensorium
CIWA-rv <10
Moderate to Severe WITHDRWAL Lasts up to 6days.
Alcoholic hallucinosis,/llusions in clear
sensorium,
Seizure: starts 6-48 hours after last drink
Delirium Tremens
Starts in 48-72 hours
May last up to 2 weeks
Sweating, tachycardia, anxiety, hallucinations,
illusions, disorientation, agitation,

38. Detoxification
Detoxification is the process of graduated reduction of a
psychoactive substance in a safe and effective manner by
either by:
gradually tapering off the substance or
substituting it with a cross-tolerant pharmacological agent
which is then tapered off.
Detoxification minimizes the withdrawal symptoms, relieves
discomfort, prevents complications and hastens the process
of abstinence from the substance.


39. Assessment
 Assessment of Severity: CIWA-Ar
 Decide Setting of management
– Hospital settings (moderate to severe cases)
– Quiet, low lit room, Qualified team
– Community Setting (for mild cases). By experienced staff
 History taking:
 Withdrawal state...........History of alcohol use
• Corroborate history
– Cessation in the past week
• Not drunk alcohol for two weeks, No withdrawal
– Symptom complex.....Sweating, Tremor, Tachycardia
– Thorough Physical exam


40. Detoxification
 Examination
 Vital signs
 All systems examined (for physical conditions)
 Complications of alcohol withdrawal states
– Delirium tremens
– Alcoholic hallucinosis
– Liver damage
– Other systems damage
 .

41. DETOXIFICATION TREATMENT
 Medications to ameliorate the symptoms of withdrawal
 Medications to prevent withdrawal seizures, reduce
agitation, make patients comfortable
 Benzodazepams have better evidence basis
 Anticonvulants used but not better than Benzos
 Benzos
 Long acting
 Short acting
 Continue to administer CIWA-Ar

42. Benzodiazepine regimes
 Fixed dose regime
– 5mg diazepam qds (Maximum 60mg/day)
– OR
– 25mg of chlordiazepoxide qds (maximum 125mg/day
– Best for Alcohol hallucinosis
– Reduce over 10-14 days
– Beloved by nurses
– Most popular

43. Benzo regimes
 Loading dose
– 20mg diazepam every 2 hours. Stop when drowsy
– Reduces complication, reduces total dose, reduces duration
 Symptom triggered
– CIWA-Ar of 8 or more = 25mg librium.
– Then when symptons arise
 Symptom Monitored
– 20mg Diazepam stat.
– Then record CIWA-Ar at intervals for further doses
Nurses don't like this regime

44. Delirium
Delirium is a clinical syndrome of acute onset, caused by
trauma/post surgery/tumuors and other medical conditions
characterized by
– Tremor
– altered sensorium (disorientation),
– perceptual abnormalities (illusions and
hallucinations)
– confused or disordered thinking,
– psychomotor agitation (or retardation)
– In Hypoactive delirium (Think 2H: hepatic and
hyponatremia)
– disturbed (usually reversed) sleep-wake cycle.
– Raised BP, HR, RR

45. Delirium Tremens or DT
 Delirium occuring in the context of alcohol withdrawal
 2-4 days after last use of alcohol
– Usually hyperactive delirium (with psychomotor
agitation)
– RULE OUT a general medical condition causing
disturbance in the basic functions of the brain.
• e.g infection, toxic, metabolic, traumatic or
endocrine disturbances.

46. Predictors of DT
Older age
Co-morbid medical conditions
High CIWA-Ar Score plus high BAL
Dehydration
History of delirium
Hyponatreamia, Hypokalaemia
Elevated ASP and GGT
Long duration of alcohol use
High average use of alcohol

47. DANGER: Delirium Tremens or DT
 Mortality is about 8%
 Manage on general medical ward
 Treat in a quiet room with minimal stimulation
– Establish IV line
• For fluid and electrolyte imbalance
• Vit B to prevent WE
– IV 2mg Lorazepam more effective than diazepam
against seizure
– IV 10mg, every 2 hours of diazepam until
somnolence
– Physical restraint may be necessary

48. Wernicke’s encephalopathy
Brain damage due to alcohol related thiamine deficiency
Triad of CONFUSION, ATAXIA OPTHALMOPLEGIA
Rarely presents with all 3 symptoms
Prevented with IV Thiamine (250-500mg per day for 3-5 days)
Mortality is 20%
Amnestic syndrome in 75%
Korsokoff’s encephalopathy

49. Post Detoxification management
RELAPSE prevention.
Biological Disulfiram
Aldehyde dehydrogenase
Alcohol.................Acetaldehyde.................Acetic acid
Alcohol dehydrogenase Aldehyde dehydrogenase
Psychological......CBT, BT, Family Therapy etc
Social....Time occupation, rehabilitation

50. Cycle of addiction
Reward
Reinforce
ment +Ve
Consumption
Reinforce
ment -ve
Naltrexone
Acamprosate
Psychotherapies
Symptomatic relief
Disulfiram

51. Bio-Psycho-Social Management Addiction
Biological Psychological Social
Predisposing
Neurobiology
prefrontal cortex
Wanting V liking
Anxiety
Low confidence
Psychotherapy
Peer pressure
to belong
Environmental
interventions
Precipitating Management of
Withdrawal states
Negative
reinforcement
Company of users
Psychotherapy
Perpetuating Disulfiram
Naltrexone +
Accamprosate
Family Therapy
Treatment failures
Rehabilitation

52. Summary
Management of all substance dependence
Predetoxification
Detoxification
Post detoxification

53. Practise short answer question
As the on-call SHO in Psychiatry, you have been asked to
assess a 52 year old man on the medical ward. He is
known to be alcohol dependent although he has not used
alcohol for 8 weeks. He presents with disorientation and
reduced psychomotor activities.
1. List 10 conditions you would want to rule out.
2. Explain why Delirium Tremens is unlikely diagnosis

54. Answer
Condition What to look for
Hyponatremia Poor oral intake
Dehydration
Hepatic Encephalopathy History of jaundice
Reversal of sleep-Wake cycle
Ascites; Parotid enlargement
Pneumonia Fever, cough
Low arterial blood saturation
Meningitis
Encephalitis
Fever, seizure (status epileticus),
Focal neurological deficits
Head injury History of unconsciousness
Bradycardia, Hypertension (raised ICT)
Pin poin pupill, Bleeding from any orifie
Thyrotoxicosis History of thyroid disease; Exopthalmos)
Overdose Anidepressants, Atropine

55. Practice essay question:
There has been a significant advancement in the treatment
of alcohol use disorders over the decades. Discuss the
current evidence based treatment of alcohol use disorder
Introduction: Acknowledge the vagaries of alcohol treatment in the past
Theme 1....General principles of management of a condition is based on the knowledge of the aetiology.
Neurscience has implicated the mesocorticolimbic structures of the brain in the aetiology of addiction
Theme 2...Outline a Biopsychosocial model of treatment
Theme 3...Outline the concept of a comprehensive management of alcohol based on pre-detox; detox; and
post detox management
Theme 4;....Any other concept
Conclusion....