MANAGEMENT OF DRUG ADDICTION / SUBSTANCE ABUSE

1. MANAGEMENT OF DRUG ADDICTION / SUBSTANCE ABUSE Dr Jacinta O’Shea Research Registrar ERHA

2. DRUG ADDICTION • Chronic relapsing disorder • Compulsive drug seeking & drug taking behaviour, despite serious negative consequences • ICD 10 Criteria • Induce pleasant states (positive reinforcer) or relieve distress (negative reinforcer) • Continued use induces adaptive changes in the CNS, leading to the development of tolerance, dependence, sensitization, craving & relapse

3. Substances of abuse • Opiods; Heroin • Alcohol • Benzodiazepines & Barbiturates • Stimulants: Cocaine & Amphetamines • Cannabinoids • Hallucinogens; LSD, Mescaline • Solvents • Nicotine

4. Patterns of Drug Use • Experimental • Recreational • Habitual • Dependant • Other: - Polysubstance use - Dual diagnosis use

5. Clinical situations • Harmful use • Dependence syndrome • Withdrawal state +/- delirium; “DT’s” • Drug induced Psychosis • Cognitive impairment syndromes • Acute intoxification • Residual disorders

6. ICD-10 Criteria • A strong desire/compulsion to take the substance • Difficulties in controlling substance-taking • A physiological withdrawal state • Evidence of tolerance • Progressive neglect of alternative pleasures • Persisting with substance use despite clear evidence of OVERTLY harmful consequences

7. Epidemiology • British Psychiatric Morbidity study 1993/2000 “ neurosis”- 160/1000 Probable psychosis – 5/1000 Personality disorder- 44/1000 Alcohol dependant- 70/1000 Drug dependant- 40/1000

8. UK Community surveys • 3o% have tried illegal drugs; 10% in last year. • <25y.o – 50% lifetime; 33% in last year. • At all ages, males have higher rates of drug use than females; M:F 3-4:1 • Use of illegal drugs commoner in: - young adults especially males, - Lower socioeconomic groups - Those with psychiatric illness - Urban areas

9. Drug use prevalence Ireland 2002/03

10. Factors influencing drug abuse and dependence • Pharmacological & physiochemical properties of drugs • Personality & Psychiatric disorder - increased risk associated with schizophrenia, BPAD, depression, ADHD. • Genetic factors (that influence metabolism and the effects of drugs)

11. Pharmacologic and physiochemical properties • Liposolubility increases the passage through the blood-brain barrier • Water solubility facilitates injection • Volatility favours inhalation in vapour form e.g aerosols / solvents • Heat resistance favours smoking e.g. cannabis • Rapid onset and intensity of effect increase the potential for abuse • A short half-life produces abrupt & intense syndromes of withdrawal

12. OPIATES • Strong narcotic analgesics • Derived from the ripe seed capsule of the poppy • Crude opium contains morphine, codeine, other alkaloids • Diamorphine (heroin) made by acetylation • Eaten, sniffed, smoked, injected

13. OPIATES • Short term effects – Euphoria, analgesia, sedation & a feeling of tranquillity • Long term effects / Repeated use – Rapid tolerance & physical dependence • Over dose – Lethal respiratory depression

14. Opiate Receptors • 3 Major opiate receptors - µ, δ, and к • 3 Endogenous opiate peptides – Encephalins, beta-endorphin, dynoorphin • Agonist action at μ and к receptors causes tolerance and dependence • Opiates activate these receptors which then couple G proteins

15. Opiates &The dopamine pathway • Natural rewards and addictive drugs stimulate the release of dopamine from neurones of the presynaptic ventral tegmental area into the nucleus accumbens, causing euphoria & reinforcement of the behaviour • Habituation ( rapid adaptive changes ) occur with natural rewards but not with addictive drugs & each dose stimulates the release of dopamine • Dopamine binds to a G-protein coupled receptor with two subtypes, D1 like, and D2 like.

16. Opiates Cont… • Most drugs that produce elevations in mood or euphoria, release dopamine in either the nucleus accumbens or the prefrontal cortex • Opiods release dopamine mainly by an indirect mechanism that decreases the activity of GABA- inhibitory neurones in the ventral tegmental area • Stimulation of κ receptors decreases dopamine levels in the nucleus accumbens and produces aversive responses • Reward & physical dependence are mediated by the activation of μ receptors

17. Opiate tolerance • Tolerance leads to increasing doses, or reduction between intervals, or both • Short term administration of opiates activates the μ-opiod Gαi/o- coupled receptor, this leads to a decrease in the number of opiod receptors and to the development of tolerance

18. Opiate withdrawal • Withdrawal causes reinstatement of drug use to prevent or decrease physical symptoms and dysphoria • Inhibition of neurones in the locus ceruleus by opiate is a key mechanism in withdrawal • When opiate levels fall the unopposed neurones lead to adrenergic over activity • Activation of к receptors in the ventral tegmental area decreases dopamine in the nucleus acumbens, leading to dysphoria and anhedonia

19. Opiate withdrawal • Grade 0 – drug craving, anxiety, drug seeking • Grade 1 – yawning, sweating, runny nose, restless sleep • Grade 2 – dilated pupils, hot and cold flushes, goose flesh (“cold turkey”), aches and pains • Grade 3 – insomnia, restlessness and agitation, abdominal cramps, N+V, diarrhoea, increased pulse , BP and RR

20. Hazards • Sterility – abscesses, septicaemia endocarditis • Adulterants – gangrene DVT and pulmonary emboli • Sharing – blood borne diseases HIV, Hepatitis B and C

21. Blood borne diseasesHIV • Currently IVDU’s account for 37% (1048) • Though the numbers of IVDU’s with HIV increased between 1998-2001, it was followed by a reduction of almost 50% during 2001-2002. This may reflect service expansion or the delay between infection and diagnosis • EMCDDA(2002) record a prevalence rate of 3.3-8.7% of HIV infection among IVDU’s between 1996-2001

22. Hepatitis C • HCV prevalence is very high in all countries and settings in Europe, with infection rates of between 40-90% among different IDU subgroups • Prevalence rates 72-73% 1996-2001 (EMCDDA) • No routine data collection in Ireland • 1st study 1995 HCV prevalence 84% - <2 years injecting 70% +ve >2 years injecting 95% +ve

23. Methadone • Synthetic opiate • Administered orally • Half-life 24-36 hrs (10-90) ; once daily dosage • Steady state 4-5 days • Dosage 30-60mg • Harm reduction approach • Maintenance / Detoxification

24. Methadone Maintenance • Used in the USA since 1960’s • Stabilises lifestyle • Harm reduction benefits 75-90% of patients • Reduces HIV, Hepatitis • Reduces crime • Aim for a dose of 60mg and over

25. Harm reduction • As opposed to Abstinence / “curing” • WHO defines Harm reduction as a concept to prevent or reduce negative health consequences associated with certain behaviours • Concerns about transmission of HIV; epidemics in >110 countries; relapsing nature of Addiction • Focuses on minimising health, personal and social harms associated with drug use - the spread of blood-borne diseases, overdoses etc • Ongoing interventions, not short term, as a way to improve health of drug users, their families and society • Marginalised groups

26. Interventions include • Information, education, communication • Education about STD’s +safer sex, family planning ; injection techniques • Health care in relation to infectious diseases; screening, immunisation • Substitution with oral drugs • Needle exchange programmes • Linking with other services – e.g. medical, psychiatric, obstetric, dental ; social and forensic • other

27. Benefits of methadone • “safe” substitution drug • Effective in engaging and retaining people in treatment • Reduces risk, reduced levels of injection • A factor in improving physical/Mental health and quality of life of patients and their families • Reduces criminal activity and demands on the criminal justice system

28. Lofexidine • Alpha-2 adrenergic agonist inhibiting noradrenaline release • Useful in short term users • Detoxify over 2-3 weeks using up to 2mg daily • Daily BP monitoring is essential • Mainly used in in-patient units

29. Naltrexone • Narcotic antagonist • Half-life 96 hours • Dose 50mg daily • Used after detoxification • Best when supervised by family • Breaks the cycle of craving

30. Alcohol • 1 unit = 10ml / 8g absolute alcohol ( ½ pint lager, glass wine, 25ml spirits) • Hydrophilic, with rapid absorption through the gut • Peak plasma levels reached 30-60 mins post ingestion • Metabolized by hepatic oxidation (ADH)

31. Neurobiology of alcohol • Stimulant at low doses, sedative at higher concentrations • Anxiolytic effects mediated by potentiation of inhibitory effects GABA at GABA-A receptors • Disturbs glutamate transmission by inhibiting NMDA receptors,- related to withdrawal seizures, DT’s etc • Unopposed action of GABA and NMDA, increasing neuronal excitability

32. Alcohol related physical problems • GIT – oesophagitis, gastritis, reflux, m-w tears, varices, pancreatitis, portal HT, ca’s • Liver – hepatitis, fatty liver, cirrhosis, haemochr, hepatic Ca, hepatic encephalopathy • Cardiovascular – arrythmias, cardiomyopathy, coronary/cerebrovascular disease, hypertension • Metabolic • Endocrine e.g. pseudocushings, hypogonadism, infertility, low libido/impotence • Musculoskeletal e.g. gout, fractures, osteoporosis • Haematological e.g. anaemia, thrombocytopaenia • Respiratory • Dermatological e.g. spider naevi, palmar erythema, eczema, worsening psoriasis

33. Alcohol – Neurological problems • Acute intoxication • Mania a potu – pathological drunkenness with minute amounts of alcohol (not in ICD-10) • Methanol poisoning • Amnesic (Korsakoff’s) syndrome & Wernicke’s encephalopathy • Cerebellar degeneration • Ambylyopia- retrobulbar neuritis; may be associated with peripheral neuropathy • Central pontine myelinosis • Dementia, amnesia/blackouts etc • Fetal alcohol syndrome

34. Psychological related disorders • Alcoholic Hallucinosis- 10-20% > 6/12 -5-20%...schizoph • Psychiatric comorbidity ECA study -psychiatric dx x3 risk of lifetime alc disor - 13% alcoholics 2nd mood disorder - 22% mood disorder also alcohol disorder • Suicide – approx 25% attempt; male, divorced, personality disorder, older, unemployed, medical issues, hx of DSH • Pathological jealousy- “Othello syndrome” • Anxiety states- panic, OCD, phobias • PTSD - alcohol dampens hyperarousal • Eating disorders – bulemia • Other drug use

35. Alcohol withdrawal • Important to recognise – 25% of male medical patients are problem drinkers • Occurs from 6-24 hours after cessation, peaking at day 2-3, highest risk in first 24-48hrs • Range of features – sweating, tremor, nausea, anorexia, vomiting, anxiety, insomnia, restlessness, hallucinations, seizures, nightmare, confusion, hallucinosis

36. Delirium tremens • Toxic confusional state with somatic disturbance, occurring in < 5% • Mortality rate of approx 10%( -20%) • Symptoms peak at 3-4 days of withdrawal • Triad of clouding of consciousness, sensory distortion and tremor • Agitation, fear and insomnia, worse at night

37. Features of DT’s • Confusion and disorientation. • Clouding of consciousness. • Delusions and hallucinations. • Psychomotor agitation and automatic dysfx. • Perceptual disturbance and fear. • Insomnia and truncal ataxia. • Electrolyte disturbance and dehydration . • Leukocytosis and disordered LFT’s. • EEG shows an increase in fast activity.

38. Treatment • Acute withdrawal – Short acting benzodiazepines; chlordiazepoxide, diazepam – minimise the risk of seizures • 40mg clordiazepoxide, 6hourly, (Max 300mg in 24hrs) • Reducing doses over 5-10 days • Consider anticonvulsants (carbamezepine) • Multivitamin preparations- Thiamine / B vitamin - Wernicke-Korsakoff psychosis • Treat infection, dehydration, suicidal ideation etc

39. In Patient Treatment • Past History of seizures or epilepsy • Comorbid severe mental illness • Intercurrent acute illness • Previous failed OPD attempts • Elderly patients

40. Post-detoxification • Disulfuram (Antabuse) – Inhibitor of aldehyde dehydrogenase. Blocks ethanol metabolism at the acetaldehyde level. ‘Flushing reaction’ • Loading dose 600-800mg per day for 3-4 days • Maintenance 200mg daily • Hypotension and MI with heavy alcohol consumption, potentially fatal • Useful in highly motivated groups and where assisted by family or friends

41. Post Detoxification • Naltrexone- Opiate receptor antagonist, thought to negate the euphoria associated with alcohol • DOSE • Acamprosate (Calcium bisacetyl homotaurine)- Synthetic GABA analogue • DOSE • SSRI’s

42. Post Detoxification • Psychological interventions; Relapse prevention, MET, cue exposure with response prevention, social skills, relaxation techniques, CBT, Family therapy etc • Alcoholics anonymous – 12 step programme • Residential rehabilitation programmes- minnisota model- social skills, relaxation, structured relapse prevention

43. Cognitive & behavioural strategies • By identifying triggers for relapse – neg/pos mood states - poor coping skills - social isolation - craving - family issues And developing global self management strategies in areas of cognitive restructuring, skills training, lifestyle changes

44. Brief intervention • Assessmint of intake • Information on harmful drinking, advice Decrease by 50%, as effective as more expensive specialist tx.

45. Motivational interviewing • Addressing ambivalence, moving through a cycle of change • 5 tenets - express empathy -help see discrepancies -avoid argument - roll with resistance - support sense of self efficacy

46. Prognosis • Poor – alcoholic brain damage, comorbidity, divorced, criminal record, low IQ, poor support and motivation • Valient 2003 – 60 yr follow up -25% dependant -Death rate x 2-3, rare after 70; predictors of positive outcome “the most and least severe alcoholics appeared to enjoy the best longterm chance of remission”

47. Cocaine • Substantial increases in drug treatment population • Increasingly reported as 2nd problem drug – 50%IV ( < benzodiazepines ) • Anecdotal reports- across general population • No substitute drug available • Some combined pharmacotherapy's; counselling, CBT, Motivational interviewing • 3% general population report lifetime use; increasing

48. Effects and risks of cocaine • Perceived as safe • Increased energy, alertness, talkative, sex drive • Combined with alcohol more toxic than either alone • Severe psychological dependence, cravings • Tolerance develops • unpleasant side effects – dry mouth, sweating, palpitations, anorexia, headaches, abd pain, irritability, paranoia, hallucinations, MI • Fatigue and depression; “crash”; mental problems; nasal / breathing problems • Increased sexual risk behaviour; association with prostitution

49. Benzodiazepines