Duncan Raistrick

Steady-state pharmacokinetics of methadone in opioid addicts

SummaryKinetic parameters were investigated in tolerant methadone maintenance patients. The disposition of methadone at steady-state was assessed on 8 occasions — in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day) — providing unique pharmacokinetic data.Statistical analysis showed that the kinetics of oral methadone at steady-state were described using a single compartment model. Analysis of the plasma concentration-time curves gave estimates of the variance of methadone clearance and apparent volume of distribution, and indicate that methadone is rapidly absorbed (mean Ka, 1.7 h−1) with a detectable increase in the plasma drug concentration 15 to 30 min after dosing.The elimination of methadone from plasma was found to occur slowly (mean t1/2 26.8 h) beginning soon after the administration of the daily oral prescription. The apparent volume of distribution — assuming the oral bioavailability (f) of methadone to be 0.95 — was large (mean 6.71 · kg−1).The slow clearance of this drug from the body (mean 3.1 ml · min−1 · kg−1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval.

Benzodiazepine misuse by drug addicts.

Using a high-performance liquid chromatography method, we measured seven commonly prescribed benzodiazepines (chlordiazepoxide, nitrazepam, nordiazepam, oxazepam, lorazepam, temazepam and diazepam) in 100 urine samples obtained from patients attending the Leeds Addiction Unit. All of the urines selected for investigation were positive for benzodiazepines using an EMIT (Enzyme Immunoassay) screen. Forty-four of the urines contained a range of benzodiazepines, none of which had been prescribed. Nitrazepam was detected most frequently (61 urine samples), but had not been prescribed to any of the patients in this study. Chlordiazepoxide was detected in 49 urine samples, although it had been prescribed to only five patients. Temazepam was detected in 28 urine samples. Fourteen patients providing 21 urine samples had been prescribed temazepam for treatment. However, temazepam was detected in only 14 of these samples. Multiple benzodiazepine abuse was evident from the high rate of detection of unrelated benzodiazepines.

The effectiveness and cost-effectiveness of opportunistic screening and stepped care interventions for older hazardous alcohol users in primary care (AESOPS) – A randomised control trial protocol

BackgroundThere is a wealth of evidence regarding the detrimental impact of excessive alcohol consumption. In older populations excessive alcohol consumption is associated with increased risk of coronary heart disease, hypertension, stroke and a range of cancers. Alcohol consumption is also associated with an increased risk of falls, early onset of dementia and other cognitive deficits. Physiological changes that occur as part of the ageing process mean that older people experience alcohol related problems at lower consumption levels. There is a strong evidence base for the effectiveness of brief psychosocial interventions in reducing alcohol consumption in populations identified opportunistically in primary care settings. Stepped care interventions involve the delivery of more intensive interventions only to those in the population who fail to respond to less intensive interventions and provide a potentially resource efficient means of meeting the needs of this population.Methods/designThe study design is a pragmatic prospective multi-centre two arm randomised controlled trial. The primary hypothesis is that stepped care interventions for older hazardous alcohol users reduce alcohol consumption compared with a minimal intervention at 12 months post randomisation. Potential participants are identified using the AUDIT questionnaire. Eligible and consenting participants are randomised with equal probability to either a minimal intervention or a three step treatment approach. The step treatment approach incorporates as step 1 behavioural change counselling, step 2 three sessions of motivational enhancement therapy and step 3 referral to specialist services. The primary outcome is measured using average standard drinks per day and secondary outcome measures include the Drinking Problems Index, health related quality of life and health utility. The study incorporates a comprehensive economic analysis to assess the relative cost-effectiveness of the interventions.DiscussionThe paper presents a protocol for the first pragmatic randomised controlled trial evaluating the effectiveness and cost-effectiveness of stepped care interventions for older hazardous alcohol users in primary care.Trial registrationISRCTN52557360

Exploring Treatment Attendance and its Relationship to Outcome in a Randomized Controlled Trial of Treatment for Alcohol Problems: Secondary Analysis of the UK Alcohol Treatment Trial (UKATT)

AIMS To identify client characteristics that predict attendance at treatment sessions and to investigate the effect of attendance on outcomes using data from the UK Alcohol Treatment Trial. METHODS Logistic regression was used to determine whether there were characteristics that could predict attendance and then continuation in treatment. Linear regression was used to explore the effects of treatment attendance on outcomes. RESULTS There were significant positive relationships between treatment attendance and outcomes at Month 3. At Month 12, these relationships were only significant for dependence and alcohol problems for those randomized to motivational enhancement therapy (MET). There were significant differences between groups in attendance, with MET clients more likely to attend than clients allocated to social behaviour and network therapy (SBNT). MET clients were also more likely to attend all sessions (three sessions) compared with SBNT (eight sessions). MET clients with larger social networks and those with confidence in their ability not to drink excessively were more likely to attend. SBNT clients with greater motivation to change and those with more negative short-term alcohol outcome expectancies were more likely to attend. No significant predictors were found for retention in treatment for MET. For those receiving SBNT, fewer alcohol problems were associated with continuation in treatment. CONCLUSION Attending more sessions was associated with better outcomes. An interpretation of these findings is that, to improve outcomes, methods should be developed and used to increase attendance rates. Different characteristics were identified that predicted attendance and continuation in treatment for MET and SBNT.

Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers

Abstract Background and aims Nalmefene has been approved in Europe for the treatment of alcohol dependence and subsequently recommended by the UK National Institute for Health and Care Excellence (NICE). This study examines critically the evidence base underpinning both decisions and the issues arising. Methods Published studies of nalmefene were identified through a systematic search, with documents from the European Medicines Agency, the NICE appraisal and public clinical trial registries also examined to identify methodological issues. Results Efficacy data used to support the licensing of nalmefene suffer from risk of bias due to lack of specification of a priori outcome measures and sensitivity analyses, use of post‐hoc sample refinement and the use of inappropriate comparators. Despite this, evidence for the efficacy of nalmefene in reducing alcohol consumption in those with alcohol dependence is, at best, modest, and of uncertain significance to individual patients. The relevance of existing trial data to routine primary care practice is doubtful. Conclusions Problems with the registration, design, analysis and reporting of clinical trials of nalmefene did not prevent it being licensed and recommended for treating alcohol dependence. This creates dilemmas for primary care clinicians and commissioning organisations where nalmefene has been heavily promoted, and poses wider questions about the effectiveness of the medicines regulation system and how to develop the alcohol treatment evidence base.

Service user, family and friends’ views on the meaning of a ‘good outcome’ of treatment for an addiction problem

Aims: The aim of this study was to investigate the views of service users (SUs), family and friends on what constitutes a good outcome for the treatment of substance misuse problems. Methods: Six focus groups were arranged to explore and identify important elements of good outcome. Transcripts of the focus groups were analysed using thematic analysis. The content of the main theme, good outcome, was cross checked with SUs and the four authors. The main theme was analysed further into sub-themes. Findings: Participants were 24 SUs and 12 family and friend members recruited from specialist drug and alcohol services. The participants represented a broad range of treatment journey experiences in a variety of treatment modalities. A total of 20 outcome elements were elicited and categorised into seven sub-themes: abstinence, health, activities, relationships, social circumstances, self-awareness and wellbeing of family and friends. Conclusions: The focus of this study was on the ideal outcome rather than intermediate outcomes that might be valuable as individual treatment goals. Considerable weight was placed, by both SUs and their family and friends, on abstinence and ways of maintaining abstinence.

Measuring Outcomes in a Health Service Addiction Clinic

The aim of the study was to identify a method for the routine monitoring of outcomes in a busy city centre health service addiction clinic. The setting for the study was a health service addiction clinic serving a population of seven hundred and fifty thousand people. Study participants were two hundred and thirty consecutive attenders for treatment of alcohol and heroin dependence and misuse. A brief interview to obtain demographic and use data and a short battery of self completion questionnaires measuring dependence, psychological health and social satisfaction were administered at three data collection points. Different methods of follow-up were explored. The instruments used were capable of measuring change in levels of consumption, degrees of dependence, psychological health and social satisfaction over a three month period in over sixty-five per cent of the original sample while over eighty per cent of the original sample were accounted for. It was concluded that routine monitoring of outcomes of a busy National Health Service can provide meaningful clinical data for an acceptable sample of patients within a realistic resource limit.

Dihydrocodeine: A useful tool in the detoxification of methadone-maintained patients

We investigated the merit of dihydrocodeine tartrate for withdrawal in detoxifying 20 methadone-maintained patients presenting for treatment at the Leeds Addiction Unit (LAU). Thirteen patients (65%) successfully completed methadone detoxification and were abstinent from both methadone and opiate-type drugs at the end of the 2-week program. On completion, three patients began treatment with Naltrexone and another was abstinent at a follow-up appointment, 1 week later. A further patient relapsed back to heroin use but remained in contact with the LAU. The remaining six patients dropped out of the 2-week detoxification program between days 3 and 11 of the dihydrocodeine cross-over period. We believe dihydrocodeine may have advantages in detoxifying methadone-maintained patients.

Medical specialists' views on the impact of reducing alcohol consumption on prognosis of, and risk of, hospital admission due to specific medical conditions: results from a Delphi survey

RATIONALE, AIMS AND OBJECTIVES To find consensus, or lack thereof, on the impact of reducing alcohol consumption on prognosis and the risk of hospital admissions for a number of alcohol-attributable disorders. METHODS A modified two-round Delphi survey utilizing web-based questionnaires to collect quantitative and qualitative data was used. Alcohol treatment experts from cardiology, emergency medicine, gastroenterology and oncology in the United Kingdom were invited to participate. The main outcomes were median impact ratings (on a scale of 1-9) and consensus (unanimous, strong, moderate, weak or no consensus). RESULTS Of 192 experts invited to participate, 59 completed first questionnaires. The overall retention rate to the second questionnaires was about 51% (30/59). There was strong support that reducing alcohol consumption could result in improvement in prognosis for gastroenterology and emergency medicine patients; but uncertainty on the benefits for cardiology and oncology patients. Overall, the responses from the expert panel did not reflect the assumption that reducing alcohol consumption would result in benefits on hospital admissions for any of the specialties. The specialists viewed the severity of disorders as important when considering the impact of reducing alcohol consumption. CONCLUSIONS The highest impact of treatment for problem drinking in hospitals is considered to be for alcohol-related disorders associated with gastroenterology and emergency medicine. At policy level, if targeted screening for alcohol problems by presenting disease or condition is the strategy of choice, it would be logical to implement screening and easily accessible interventions or addiction specialists within these areas where alcohol treatment is considered as having a high impact.

Attitudes of healthcare professionals in a general hospital to patients with substance misuse disorders

Abstract Aims and method: To repeat a survey (reported 2007) of the attitudes of staff in a general hospital setting towards working with people who have substance misuse problems. Therapeutic attitude and the frequency of undertaking tasks related to dealing with substance misuse problems were measured using a modified version of the Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ). The questionnaire was given to staff on wards in general hospitals where people with substance misuse problems are commonly admitted. Results: The questionnaire return rate of 24% was lower than 2007 and the possible reasons are discussed. Doctors, nurses and healthcare assistants all reported low levels of therapeutic commitment and lower than 2007. Older doctors scored the lowest and younger doctors highest. Brief training seemed to have a positive effect. Implications: The authors conclude that there should be a policy shift away from trying to “piggy back” care of people with substance misuse problems onto practitioners in other clinical specialties. Although addiction problems are found in most areas of health and social care, the role of staff in treating addiction is limited – effective substance misuse treatment is best delivered by trained addiction practitioners.