Dr James Bell Ms Fiona Kennedy Ms Chris Healey Dr Mohammad Faizal Dr Lynn Owens Dr Sreedharan Nagendran Dr Steve Hood New care pathways for managing dependent drinkers

Why is this research important? Over the last 2 decades there has been a measureable increase in alcohol-related liver disease, and a more difficult to measure increase in other adverse consequences of alcohol dependence. Alcohol-related diseases and social marginalisation place a large burden on the NHS. There has been limited integration of addiction services, hospitals and primary care. A recent report (NCEPOD 2013) has called for the establishment of consultant-led teams of alcohol nurses in general hospitals to try to manage alcohol better, and provide an opportunity to intervene to minimize the future burden of disease resulting from alcohol misuse. In the light of this recommendation, it is useful to evaluate some innovative alcohol pathways that have been developed in recent years.

Aims and Objectives: To describe two acute care pathways for dependent drinkers presenting to ED: 1)Hospital liaison service and ambulatory clinic (LCAS, Royal Liverpool) 2)Hospital liaison service and immediate transfer to IP unit (AAU unit, London) To compare characteristics (demographics, severity of dependence, GGT values (proportion abnormal), prior Rx history of patients attending these pathways with people presenting for elective management of alcohol dependence: 1)Elective detoxification clinic (Windsor Clinic, Liverpool) To compare the outcomes of the acute and elective pathways in terms of time to first drink post treatment, attendance for aftercare, and presentation to ED in the 3 months after treatment We also sought to identify potential predictors of good outcomes.

Sampling: Windsor Clinic AAU Unit 50 participants recruited LCAS 46 participants recruited 77 Participants recruited Telephone Interviews conducted with 57/77 participants (74%) Telephone Interviews conducted with 17/50 participants (34%) Telephone Interviews conducted with 26/46 participants (57%)

Research Outcomes Demographics: Demographically, participants from all three pathways were very similar: Mean age – 45 Majority of participants were male (around 70%) Majority of participants at all three pathways were unemployed. Most of the participants were single. Drinking history and alcohol dependence: Most participants drank between 200 and 250 units of alcohol per week on admission. Participants who were admitted to the AAU unit tended to consume a larger number of units of alcohol per week than those at LCAS or the Windsor Clinic. Most participants at all three pathways had a severe dependence on alcohol according to the SADQ model (31+). The SADQ scores recorded for participants were higher at the Windsor Clinic than the other two pathways.

Concomitant mental and physical history: 41% of participants were prescribed anti-depressants. 24 % of participants had a history of self harm. Participants who were recruited from the London pathway were significantly more likely to have a history of self harm than those recruited from either the Windsor Clinic or LCAS. 39% of participants had a history of seizures. Participants who were recruited from the KHP pathway were also significantly more likely to have a history of seizures. Treatment Process: Most participants completed detox and were referred aftercare (either within the unit or in the community).

Three month follow up: Self reported abstinence at 3 month follow up (if assuming that participants we were unable to get hold of have relapsed), 30% of participants who had been treated at the ambulatory detox pathway (LCAS) were still abstinent 3 months post treatment, 12% from London, 18% from Windsor Clinic. 18% of participants who had been treated at Windsor Clinic had relapsed within 8 days of leaving treatment, while at London this was slightly lower (but still significant) at 10%. At LCAS, this accounted for 4% of participants. For those participants who had relapsed within 8 days of being discharged, the number of times they attended ED significantly increased in the 3 month period post treatment. 35% of participants attended aftercare. Participants were much more likely to have attended aftercare if they were treated on the ambulatory detox pathway (LCAS). The LCAS team offered their own aftercare in the form of alcohol clinics within the hospital. This was not offered by either of the other two pathways.

Qualitative Findings (3 month follow up telephone interviews): The majority of participants found the treatment helpful. The most commonly reported positive aspect of the care was the staff. Although most participants found the treatment helpful, they did suggest ways that it could be improved. These included: 1)More readily available aftercare 2)Longer treatment 3)Medication for longer

Implications for future research: Demographically, patients were very similar at all three pathways. The ambulatory detox model is as successful as in-patient detox in terms of hospital readmission within 3 months but seems to be more successful in terms of abstinence rates. Participants were much more likely to have remained abstinent after 3 months if they had attended the ambulatory detox model. However, ambulatory detox is not suitable for all patients. Some will still need inpatient treatment. A lot of patients relapsed after inpatient detox within 1 week.

We now propose conducting a quality-improvement initiative study combining some parts of the ambulatory detox model with inpatient detox programs to try and improve abstinence rates. This will be done at Windsor Clinic in Liverpool and the AAU unit in London and will include: 1)A doctor will see the patient 24 hours prior to discharge to discuss follow up plans and arrange an appointment 2)The patient will then be seen by an already familiar doctor/nurse within 3 days of discharge. 3)Depending on clinical need, patients will be seen again 1 week later, then 3/4 weeks later. 4)Further follow up management (if required) such as support from community agencies and prescribing medication, then this will be initiated at the earliest opportunity. Implications for future research (2):

Service Evaluation Anti-Craving Clinic Windsor Clinic Number of Patients evaluated: 102

Demographics Gender 51% of the patients were male. 49% were female. Age of Patients Mean – 46 Minimum – 25 Maximum – 70

Alcohol Dependency The majority of patients who were commenced on anti-craving medication (80.5%) had a severe dependency on alcohol.

Prior History of Alcohol detoxs Nearly 80% of the patients who were commenced on anti-craving medication had previously been an inpatient at the Windsor Clinic. 48% of all patients had attended the Windsor Clinic only once in the past, however some patients had stayed at the Windsor Clinic 5 times or more (6%).

Co-morbid Medical History Nearly 80% of patients suffered from a mental health problem: 48% of patients suffered from depression 30.3% of patients suffered from anxiety 16.6% of patients had self-harmed in the past 36% of patients had a pre-existing physical health condition.

Use of Anti-Craving medication Patients were commenced on either Acamprosate, Disulfirum or Naltrexone: MedicationNo of patients% of patients Acamprosate7876.5% Disulfirum1211.8% Naltrexone1211.8%

Abstinence Rates 40% of patients remained abstinent throughout the anti-craving treatment: Time periodNo of patients% of patients < 1 month1615.7% < 2 months1312.7% < 3 months1110.8% Over 3 months2120.6% Still Abstinent %

Alcohol Toxic and dependant drug Mood effect Aggression and violence Coma, respiratory depression, death, drowsiness Psychiatric disorders Associated with a number of physical illness 3 rd leading cause of disability after tobacco and hypertension Memory problems

NICE Guidance Diagnosis and clinical management of alcohol related physical complications (CG100) Diagnosis, assessment and management of harmful drinking and alcohol dependence (CG115)

Medications for relapse prevention Effective, but limited use Acamprosate and Disulfiram licensed in UK Naltrexone only recently licensed in UK but widely used elsewhere (e.g. US, Australia) Nalmefene recently licensed Not licensed in under 18s or pregnancy Precise mechanisms of medications not fully understood Baseline U&E and LFTs, FBC, ECG Should be used in conjunction with psychosocial interventions Compliance issues

Brain Chemistry Dopamine increase - pleasurable effect of alcohol Reward pathway Alcohol dependence – dopamine system responds to cues & motivates to drink Increased dopaminergic activity – encourages person to seek alcohol ( ? craving ) Role switches from pleasure to alcohol seeking

Opioids Alcohol increases opiates in brain This in turn increases the dopaminergic activity Opioid blockers – naltrexone, nalmefene GABA – Inhibitory or calming system in the brain GABA –B stimulation reduces dopaminergic activity in the brain ( Baclofen ) GABA –A stimulation increases inhibitory system ( BDZ/ LIBRIUM ) Serotonergic system – effect of alcohol on it not fully understood Consistent demonstration of reduced serotonergic activity

Acamprosate NMDA ( glutamate systems ) antagonist, GABA agonist 19 RCTs; high quality Moderate to severe dependnece PSI interventions used ( alcohol counselling, medication management, relapse prevention ) Superior to placebo in abstinence and relapse to heavy drinking ( meta analysis ) Most studies conducted in Europe with one in UK Commenced soon after withdrawal or during assisted withdrawal Abstinence effect most pronounced at 6 months but remained significant up to 12 months Numbers relapsing to heavy drinking was also significantly less in acamprosate group

NICE – The Quality of evidence for acamprosate is high Start after withdrawal; dose mg Continue up to 12 months, monthly supervision Side effects: diarrhoea, abdominal pain, nausea vomiting, pruritis Contraindicated: pregnancy, breast feeding, renal and hepatic failure Start ASAP after withdrawal period Takes 5 days to reach steady blood levels ? improve sleep due to its glutamate activity

Disulfiram Aldehyde dehydrogenase blocker Start 24 hrs after detox Dose : 200mg Side effects: interactions with alcohol, wide range of drugs, drowsiness, nausea, vomiting, halitosis, loss of libido psychotic reactions, peripheral neuritis, liver failure Contraindications: renal failure, hepatic or respiratory, diabetes, severe personality disorder, suicide risk, psychosis

Evidence : Very few good quality studies available NICE: Decided to use open label studies due to lack of good quality RCT Ethical issue – Due to ethanol – alcohol interaction, studies had to be open label 3-4 trials in meta analysis Most studies in US, 2 in India, I in UK Most studies are old and poor quality Likely to increase the time until participants drank any alcohol and number of abstinence days in comparison with naltrexone and placebo. Psychological effect of knowing they were taking disulfiram may have contributed to above effect NICE : Quality of effect is moderate Start at least 24 hours after the last alcoholic drink

Naltrexone Opioid antagonist ( Not to prescribe if on opiates ) 27 RCTs; high quality Superior to placebo in relapse to heavy drinking and no. heavy drinking days Start after withdrawal; dose 25 -> 50mg Continue up to 12 months, monthly supervision Side effects: nausea, abdominal pain, reduced appetite, tiredness, hepatotoxicity in high doses, opioid blockade Higher dropouts Contraindications: liver failure, renal failure, opioid medication Mild to moderate dependence (acamprosate group had more severe dependence ) NICE – Quality of evidence high Start ASAP after withdrawal period

Baclofen GABA –B agonist Muscle relaxant, treat spasticity High doses can cause ataxia, drowsiness ( above 80mg ) ?Baclofen withdrawal syndrome ? recreational use Gradual titration recommended

Overdose baclofen Prominent features are signs of central nervous depression eg drowsiness, impairment of consciousness, respiratory depression, coma. Also liable to occur are confusion, hallucinations, agitation, accommodation disorders, absent pupillary reflex; generalised muscular hypotonia, myoclonia hyporeflexia or areflexia; convulsions; peripheral vasodilation, hypotension, bradycardia; nausea, vomiting, diarrhoea, hypersalivation; elevated LDH, SGOT and AP values. A deterioration in the condition may occur if various substances or drugs acting on the CNS eg alcohol, diazepam, tricyclic antidepressants, have been taken at the same time. Symptoms may occur at lower dosages in patients with impaired renal function or in the elderly.

Note Not everyone benefits from pharmacology Predictors of outcome – difficult ( post hoc analyses looking at outcomes and clinical variables ) Conclusion : acamprosate is potentially effective for anyone with dependence

How long to continue Most trials between 3 and 6 months Many relapse within months to years Limited evidence to guide the length of treatment Stop if dependant pattern (acamprosate & Naltrexone) Disulfiram – discontinue if any evidence of drinking Continuation beyond 1 year need to be justified