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

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

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.

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

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

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.

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.

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

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.

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

AETIOLOGY

“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

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

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

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

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

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

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

ALCOHOL

Epidemiology Alcohol consumption ↑, costs Scotland > £1 billion/year M/F ratio 2/1,trend towards ↑drinking in young women 16-19 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.

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

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

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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.

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

Delirium Tremens Severe withdrawal state – medical emergency Reduced or stopped drinking.. 48-72hrs 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.

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

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

Wernicke – Korsakoff syndrome

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

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

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)

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

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)

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

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.

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 26% Long Term Care 28% slight recovery 25% sig. recovery 21% complete recovery

Treatment Prophylaxis - all inpt detox 1 pair iv/im 3-5 days Treatment 2 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

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

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.

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

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.

DRUGS

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

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”

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,

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

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

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

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

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

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!!!!!

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

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

MANAGEMENT PRINCIPLES

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

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”

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

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”

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

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

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

THANK YOU