Papropies and Withdrawal Symptoms

Transcription

1 Summary of Pharmacotherapies CPD for Psychiatric Trainees Duncan Raistrick Leeds Addiction Unit

2 definition and guidance

3 What... Detoxification Detoxification is the process of rapidly achieving a drug free state normally 7-14 days. It is different to slow reduction programmes and requires good preparation work between therapist and service user. When... Action stage: self efficacy, self esteem and positive outcome expectancy or expedience Where... Assess risk and determine level of supervision required

4 British Association of Psychopharmacology 2012: Strength of BAP recommendations rated A to D based on evidence NICE Guidelines on Alcohol Use Disorders: 2011 Diagnosis, assessment and management of harmful drinking and alcohol dependence 2010 Diagnosis and clinical management of alcohol-related physical complications 2010 Preventing harmful drinking summarising guidelines...

5 Risk 1 manifestation of withdrawal History of seizures History of delirium Exceptionally high dosage particularly short acting depressant drugs Poly drug use Poly pharmacy

6 Risk 2 pre-existing conditions Hypertension or ischaemic heart disease Significant liver or renal impairment Diabetes Mental illness including organic brain damage Elderly and debilitated Pregnancy

7 Risk 3 support and supervision Lack of a non using support person Lack of person willing to supervise medication Childcare difficulties Distance to and inaccessibility of clinics

8 Detoxification Preparation Preparation is based on a dialogue between the keyworker, service user and other carers. o Determining readiness for detoxification and highlighting positive outcomes. o Coping strategies other than pharmacotherapy for dealing with withdrawal symptoms. o Identifying a support person and plan for the detoxification period. o Identifying a post detoxification plan. o Revisiting learning points from previous detoxifications. o Assessing risks. o Making a follow on keyworker appointment.

9 basic pharmacotherapy

10 Alcohol Withdrawal Symptoms Tremulousness (6-12hrs) Seizures (24-36 hrs) Delirium (48-72 hrs) Most Common Most Specific 1 Depression Whole body shakes 2 Anxiety Facial tremulousness 3 Irritability Hand and finger shakes 4 Tiredness Cannot face the day 5 Craving Panicky 6 Restlessness Guilt 7 Insomnia Nausea 8 Confusion Visual hallucinations 9 Sweating Weakness 10 Weakness Depression Source: Hershon (1977) J Stud Alc

11 Treatment of uncomplicated withdrawal... Benzodiazepines are efficacious in reducing signs and symptoms of withdrawal (A); fixed-dose regimens are recommended for routine use with symptom-triggered dosing reserved for use only with adequate monitoring (D) Carbamazepine has also been shown to be equally efficacious to benzodiazepines (A) Clomethiazole is reserved for inpatient settings only after due consideration of its safety (A)

12 Treatment of complicated withdrawal... Seizures Benzodiazepines, particularly diazepam, prevent de novo seizures (A) Anticonvulsants are equally as efficacious as benzodiazepines in seizure prevention, but there is no advantage when combined (A) In preventing a second seizure in the same withdrawal episode, lorazepam but not phenytoin has been shown to be effective (A) Delirium Benzodiazepines, particularly those with longer half-life prevent delirium (A) and should be used for treatment (B)

13 General Methods of Detoxification Front loading Repeat dosage eg for alcohol diazepam 20mg every 90min until severity of withdrawal score below preset level. No further medication given. Efficient in staff time and reduces total dose. Fixed dose reduction A predetermined regimen for a given severity of withdrawal. Does not require experienced staff. Not sensitive to need and unlikely to pick up complications. Variable dose reduction Dose of medication is determined by the severity of withdrawal. Requires experienced and trained staff. Best method where the course of detoxification is uncertain.

14 Typical Withdrawal Medication Chlordiazepoxide (or diazepam in half the dose) severe withdrawal 30mg qds reduce over 5days moderate withdrawal 20mg qds reduce over 5days Oxazepam (liver disease) severe withdrawal 30mg qds reduce over 5days moderate withdrawal 20mg qds reduce over 5days Lorazepam (seizures or delirium) 30mcg/kg = mg IM or slow IV repeat 6hrly Chlormethiazole (in patient only) very severe withdrawal with history of seizures/delirium 2-4 caps day1 6-8 day2 reduce over 9days Oxcarbamazepine (2 nd line drug) mg daily reducing over 5days

15 Prevention of Neurotoxicity there is insufficient clinical trial evidence to include in guidance Acamprosate may be effective at blocking the neurotoxicity caused by glutamate during alcohol withdrawal other anti-glutamatergic agents also effective Mifepristone may be effective at blocking the neurotoxicity caused by corticosterone during alcohol withdrawal there are other possible targets to block the stress reaction

16 In alcohol withdrawal the brain is both over-stimulated (high glutamate) and under-inhibited (low GABA). Too much glutamate may cause cell death. Acamprosate may reduce this damage during alcohol withdrawal. Dead Control Alcohol Withdrawal Alcohol Withdrawal + Acamprosate Alive courtesy of Prendergast & Littleton

17 Opiate Withdrawal Syndrome Withdrawal symptoms Runny eyes and nose Hot and cold sweats Dilated pupils Stomach cramps and diarrhoea Muscle aches Insomnia Detoxification Buprenorphine Lofexidine and symptomatic Dihydrocodeine (rarely effective but simple) Methadone (rarely effective slow reduction)

18 Buprenorphine vs Lofexidine Acceptability SOWS days 1-5, GHQ at completion, and TPQ at 1 month follow up n = Mean Standard deviation Difference Day 1 SOWS Lofexidine Buprenorphine Day 2 SOWS Lofexidine Buprenorphine Day 3 SOWS Lofexidine Buprenorphine Day 4 SOWS Lofexidine Buprenorphine Day 5 SOWS Lofexidine Buprenorphine ** 4.21** 5.04** Completion Lofexidine GHQ Buprenorphine month Lofexidine TPQ Buprenorphine Randomised plus choice groups * p<0.01 **p<0.001 Source: Raistrick et al. (2005) Addiction

19 Total withdrawal severity Severity of methadone withdrawal linear reduction from variable starting dose of methadone Severity and duration of withdrawal from a long acting opiate methadone is not suited to detox Days 10 day sample 21 day sample Source: Gossop, M. et al (1989) British Journal of Psychiatry

20 relapse prevention

21 Relapse prevention - guidance is inconsistent and needs clinical view... Offer pharmacotherapy to everyone (A) Acamprosate improves abstinence rates (A) and reduces alcohol consumption (A) Naltrexone and (nalmefene) reduce risk of lapse becoming a relapse - less evidence of maintaining abstinence (A) Disulfiram to maintain abstinence if no contraindications (B) Baclofen to maintain abstinence if high levels of anxiety (C) SSRIs should be avoided Source: BAP (2012) J Psychopharmacology

22 Alcohol Neurochemistry The pharmacology of alcohol is not well understood. There are four known effects of alcohol albeit these may be partial effects. Acamprosate has one agonist and one antagonist effect just like alcohol. It is not itself intoxicating any effect is by changing the natural tonic status of GABA and glutamate systems. The rationale for naltrexone is that it blocks the mu effect of alcohol and so is only needed when drinking occurs.

23 Acamprosate vs Disulfiram vs Naltrexone a randomised controlled trial Days to Heavy Drinking Days to Drinking Days Abstinence /wk Acamprosate Disulfiram Naltrexone 243 subjects randomised 1:1:1 supervised medication + manualised CBT. Alcohol consumption reduced from approx 580gm weekly to 195gm (ACA) 109gm (DIS) 229gm (NTX) at 2yr follow-up Source: Laaksonen et al. (2008) Alcohol and Alcoholism

24 Disulfiram blocks aldehyde dehydrogenase causing a build up of acetaldehyde blocks dopamine-bhydroxylase causing a build up of dopamine Caution in psychotic mental illness Caution with cardiovascular disease

25 psychiatric and addiction drug interactions

26 1st interaction type exacerbate mental illness For example PSYCHOSIS and drugs causing psychosis: Opiates Dextromoramide Pentazocine Stimulants Cocaine Amphetamine Depressants Alcohol Cannabis Hallucinogens LSD Ketamine Mushrooms

27 Antipsychotics all block dopamine. All have effects at other receptors which gives each its individual profile. Olanzapine is most likely to cause metabolic syndrome.

28 Caused by: Genetics Methadone Alcohol (high BAC) Antipsychotics Antidepressants Citalopram Mirtazepine Amitriptyline 2nd interaction type irregular heart beat Statins Antihistamines

29 The heart does not pump blood properly. At worst may be cardiac arrest.

30 Caused by: Alcohol misuse Over eating Atypical antipsychotics Clozaril Olanzapine Quetiapine Risperidone Gabapentin 3rd interaction type metabolism Paroxetine (+ SSRIs)

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32 4th interaction type enzyme effects - induction Alcohol Cigarette smoking Carbamazepine Phenytoin Rifampicin Phenobarbitone Cabbage Broccolli Brussels sprouts Cauliflower Charbroiled meats Oregano

33 4th interaction type enzyme effects - blockers General (CYP450) Cimetidine/Ranitidine Diazepam SSRI antidepressants Some anti virals St John s Wort (herbal antidepressant) Chamomile Grapefruit juice Specific Disulfiram Metronidazole

34 As with antipsychotics, antidepressant effects are not usually specific. Some also have a generalised enzyme blocking effect. enzyme blocking

35 Blocks alcohol metabolism Blocks dopamine metabolism

36 the abc model

37 The ABC Model of Behaviour detox reinforces expectations that detox is effective and reinforces abstinence Antecedent cue or trigger + Expectation from detox Behaviour (substance use) Consequence withdrawal symptoms expected or present withdrawal avoided or relieved by medication drinking or drug use less likely absence of withdrawal symptoms

38 The ABC Model of Behaviour disulfiram a) reinforces belief in coping skills for abstinence b) punishment of drinking and changed expectation Antecedent cue or trigger + Expectation Behaviour (substance use) Consequence high risk situation for drinking drinking will cause unpleasant feeling a) abstinence b) risk drinking a) maintain abstinence b) alc/disulfiram reaction

39 The ABC Model of Behaviour naltrexone a) reinforces belief in coping skills for abstinence b) no opiate effect and changed expectation Antecedent cue or trigger + Expectation Behaviour (substance use) Consequence high risk situation for opiate use taking opiates will have no effect a) abstinence b) try opiates a) maintain abstinence b) no opiate effect