Mediational Analyses of the Effects of Social Behaviour and Network Therapy on Alcohol Use.

INTRODUCTION: Social behaviour and network therapy involves an active participation of the practitioner in recruiting a supportive network to change the client's alcohol use. Despite achieving beneficial effects on alcohol consumption, its possible mechanisms of change are a relatively under-studied topic compared to those of other alcohol treatment interventions. This study aimed to explore therapist skills through which social behaviour and network therapy may achieve effects on alcohol consumption in comparison with motivational enhancement therapy. METHODS: This study was secondary analysis of data from the UK Alcohol Treatment Trial, a multicentre, pragmatic, randomized controlled trial. The sample comprised 376 participants randomized to motivational enhancement therapy or social behaviour and network therapy. We used the UK Alcohol Treatment Trial Process Rating Scale to assess therapist skills. Outcomes drinks per drinking day and percentage of days abstinent were assessed 12 months after treatment initiation. Analyses were conducted in a simple mediation framework. RESULTS: Therapist skills score (combining frequency and quality) for involving others in behaviour change mediated social behaviour and network therapy effects on percentage of days abstinent (b = 0.06, 95% CI: 0.02; 0.10, p = 0.01). The frequency with which therapists acted as an active agent for change also mediated the effects of social behaviour and network therapy on percentage of days abstinent (b = 0.03, 95% CI: 0.003; 0.05, p = 0.03). The frequency with which the therapist stressed social support as a key factor in achieving change unexpectedly mediated an increase in drinks per drinking day (b = 0.10, 95% CI: 0.01; 0.18, p = 0.02). The two latter mediation effects were not sustained when quality was considered. All other indirect effects tested were non-significant. DISCUSSION/CONCLUSIONS: How social behaviour and network therapy exerts effects on alcohol outcomes is not yet well understood and in this study was not attributable to observed ratings of therapist treatment-specific skills. Therapist skill in planning the involvement of others during treatment, however, warrants further study. We suggest that the present findings should be regarded as hypothesis generating as it identifies specific targets for further investigation in alcohol treatment process studies.

Serial mediation analysis of treatment-specific processes in two contrasting alcohol treatments.

INTRODUCTION: This study explored whether treatment-specific processes linking therapist behaviors, post-session client ratings, and 3-month proximal outcomes (i.e., end of treatment) can explain 12-month outcomes for two contrasting alcohol treatment conditions with equivalent overall outcomes. METHODS: This study is a secondary analysis of the UK Alcohol Treatment Trial (UKATT), a multi-center randomized controlled trial of treatment for alcohol problems comparing 3-session motivational enhancement therapy (MET) to 8-session social behaviour and network therapy (SBNT). Among 742 adult clients included in UKATT, 351 had one treatment session recorded and coded and were followed-up 3 and 12 months after baseline. The study team conducted serial mediation analyses to test whether the frequency and quality of MET and SBNT skills were related to 12-month alcohol outcomes (drinks per drinking day) through postsession client ratings of treatment progress (Processes of Change Questionnaire, PCQ), readiness to change (RTC) and social support for drinking after 3-months. RESULTS: Higher quality of MET skills was related to higher PCQ scores, which were in turn related to greater post-treatment RTC, and subsequently to better alcohol outcomes. Total indirect effect was consistently significant. In contrast, only PCQ was predictive of treatment outcome in the SBNT portion of the model. CONCLUSIONS: This study provides evidence from a large pragmatic trial that the quality of MET skills positively influences alcohol outcomes in part through improvements in motivation during treatment and actively trying to change when treatment ends. Research should explore the ways in which SBNT secured outcomes that were equivalent to MET.

The appropriateness of psychotropic medicines: an interview study of service users attending a substance misuse service in England.

Background Mental health problems are common in people with substance misuse problems. However, there is a paucity of evidence regarding prescribing of psychotropic medications for people with comorbid mental health and substance misuse problems. Objective To explore the views of service users attending an addiction service on the appropriateness of psychotropic medications prescribed for their co-existing mental health problems. Setting A specialist addiction service in the North of England. Method A phenomenological approach was adopted. Semi-structured interviews were conducted with twelve service users. Data were analysed using thematic framework analysis. Main outcome measure Service users' views concerning the appropriateness of their prescribed psychotropic medications. Results The following themes captured service users' views on the appropriateness of their medications: benefits from medicines, entitlement to medicines, and assessment and review. Service users mostly described benefits from their medications (including those prescribed outside guideline recommendations) and there was also an awareness of the adverse effects they experienced from them. It appears that people with substance misuse problems have a particularly strong sense of their own needs and seek to influence prescribing decisions. Service users further described varied practices regarding assessment and review of their medications with evidence of regular reviews while others identified suboptimal or inadequate practices. Conclusion Most service users described improved functioning as a result of their prescribed psychotropic medications. Prescriptions that are inappropriate in terms of their usual indications may well be justified if they assist in stabilising service users and moving them on to recovery.

Prescribers' views and experiences of assessing the appropriateness of prescribed medications in a specialist addiction service.

Background Mental and physical health problems are common in people with substance misuse problems and medications are often required in their management. Given the extent of prescribing for service users who attend specialist addiction services, it is important to consider how prescribers in this setting assess the appropriateness of service users' prescribed medications. Objective To explore prescribers' views and experiences of assessing the appropriateness of medications prescribed for service users coming in for treatment as well as the differences between prescribers. Setting A specialist addiction service in the North of England. Method A phenomenological approach was adopted. Semi-structured interviews were conducted with four nurse prescribers and eight doctors. Data were analysed using thematic framework analysis. Main outcome measure Prescribers' views and experiences of assessing the appropriateness of prescribed medications. Results Assessment of the appropriateness of prescribed medications involved reviewing medications, assessing risk, history-taking, involvement of service users, and comparing guideline adherence and 'successful' prescribing. Doctors and nurse prescribers assessed the appropriateness of medications they considered to be within their competency. Doctors provided support to nurse prescribers and general practitioners (GPs) when dealing with issues around prescribing. Conclusion Assessment of the appropriateness of prescribed medications is complex. The recent reduction in medical expertise in specialist addiction services may negatively impact on the clinical management of service users. It appears that there is a need for further training of nurse prescribers and GPs so they can provide optimal care to service users.

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

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.

ADAPTA: A pilot randomised controlled trial of an alcohol-focused intervention versus a healthy living intervention for problem drinkers identified in a general hospital setting.

AIM: To examine the relative feasibility, acceptability, applicability, effectiveness and explore cost-effectiveness of a healthy living focused intervention (HL) compared to an alcohol-focused intervention (AF) for problem drinkers identified in hospital. METHODS: A pragmatic, randomised, controlled, open pilot trial. Feasibility and acceptability were measured by recruitment, attrition, follow-up rates and number of treatment sessions attended. Effectiveness was measured using the Alcohol Use Disorders Identification Test score at six months. Additional economic and secondary outcome measures were collected. RESULTS: Eighty-six participants were randomised and 72% (n=62) were retained in full participation. Forty-one participants attended at least one treatment session (48%). A greater proportion in the HL group attended all four treatment sessions (33% vs 19%). Follow-up rates were 29% at six months and 22% at twelve months. There was no evidence of a difference in AUDIT score between treatment groups at six months. Mean cost of health care and social services, policing and the criminal justice system use decreased while EQ-5D scores indicated minor improvement in both arms. However, this pilot trial was not powered to detect differences in either measure between groups. CONCLUSIONS: While no treatment effect was observed, this study demonstrated a potential to engage patients drinking at harmful or dependent levels in a healthy living intervention. However, recruitment proved challenging and follow-up rates were poor. Better ways need to be found to help these patients recognise the harms associated with their drinking and overcome the evident barriers to their engagement with specialist treatment.

Measuring clinically significant outcomes - LDQ, CORE-10 and SSQ as dimension measures of addiction.

Aims and method To determine values for reliable change and clinically significant change for the Leeds Dependence Questionnaire (LDQ) and Social Satisfaction Questionnaire (SSQ). The performance of these two measures with the Clinical Outcomes in Routine Evaluation (CORE-10) as three dimension measures of addiction was then explored. Results The reliable change statistic for both LDQ and SSQ was ⩾4; the cut-offs for clinically significant change were LDQ ⩽10 males, ⩽5 females, and SSQ ⩾16. There was no overlap of 95% CIs for means by gender between 'well-functioning' and pre- and post-treatment populations. Clinical implications These data enable the measurement of clinically significant change using the LDQ and SSQ and add to the evidence for the performance of the LDQ, CORE-10 and SSQ as dimension measures of addiction. The CORE-10 and SSQ can be used as treatment outcome measures for mental health problems other than addiction.

Developing a web-based intervention to increase motivation to change and encourage uptake of specialist face-to-face treatment by hospital inpatients: change drinking.

INTRODUCTION AND AIM: Problem drinking is rarely identified unless health-care professionals are specifically instructed to assess alcohol consumption. Individualised web-based alcohol interventions provide opportunities to enhance screening and early identification. We aimed to create a web-based brief personalised feedback intervention to enable client-centred screening and self-referral by problem drinkers recently admitted to hospital. DESIGN AND METHODS: To increase transparency of the development process, this short report describes the theoretical underpinnings and development of ChangeDrinking including identification of needs and matching with resources, screening tool selection, and look and feel. RESULTS: The website structure and content was modelled on motivational dialogue. ChangeDrinking is closely coupled to an independent questionnaire management system; this architecture enables internal logic to allow branching based on dynamic user inputs. The motivational underpinnings led to development of personalised predetermined dialogue with strong theory-practice links. Applying principles of conveying empathy and reflection was challenging within the confines of a predetermined dialogue. Reflective listening in ChangeDrinking does not extend to inviting statements of resistance to be entered. DISCUSSION AND CONCLUSIONS: ChangeDrinking has become an optional component of routine treatment for patients with an alcohol-related admission in two large UK National Health Service general hospitals.

Factor analysis of treatment outcomes from a UK specialist addiction service: relationship between the Leeds Dependence Questionnaire, Social Satisfaction Questionnaire and 10-item Clinical Outcomes in Routine Evaluation.

INTRODUCTION AND AIMS: To examine the relationship between three outcome measures used by a specialist addiction service (UK): the Leeds Dependence Questionnaire (LDQ), the Social Satisfaction Questionnaire (SSQ) and the 10-item Clinical Outcomes in Routine Evaluation (CORE-10). DESIGN AND METHOD: A clinical sample of 715 service user records was extracted from a specialist addiction service (2011) database. The LDQ (dependence), SSQ (social satisfaction) and CORE-10 (psychological distress) were routinely administered at the start of treatment and again between 3 and 12 months post-treatment. A mixed pre/post-treatment dataset of 526 service users was subjected to exploratory factor analysis. Parallel Analysis and the Hull method were used to suggest the most parsimonious factor solution. RESULTS: Exploratory factor analysis with three factors accounted for 66.2% of the total variance but Parallel Analysis supported two factors as sufficient to account for observed correlations among items. In the two-factor solution, LDQ items and nine of the 10 CORE-10 items loaded on the first factor >0.41, and the SSQ items on factor 2 with loadings >0.63. A two dimensional summary appears sufficient and clinically meaningful. DISCUSSION AND CONCLUSIONS: Among specialist addiction service users, social satisfaction appears to be a unique construct of addiction and is not the same as variation due to psychological distress or dependence. Our interpretation of the findings is that dependence is best thought of as a specific psychological condition subsumed under the construct psychological distress.

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.

An alcohol-focused intervention versus a healthy living intervention for problem drinkers identified in a general hospital setting (ADAPTA): study protocol for a randomized, controlled pilot trial.

BACKGROUND: Alcohol misuse is a major cause of premature mortality and ill health. Although there is a high prevalence of alcohol problems among patients presenting to general hospital, many of these people are not help seekers and do not engage in specialist treatment. Hospital admission is an opportunity to steer people towards specialist treatment, which can reduce health-care utilization and costs to the public sector and produce substantial individual health and social benefits. Alcohol misuse is associated with other lifestyle problems, which are amenable to intervention. It has been suggested that the development of a healthy or balanced lifestyle is potentially beneficial for reducing or abstaining from alcohol use, and relapse prevention. The aim of the study is to test whether or not the offer of a choice of health-related lifestyle interventions is more acceptable, and therefore able to engage more problem drinkers in treatment, than an alcohol-focused intervention. METHODS/DESIGN: This is a pragmatic, randomized, controlled, open pilot study in a UK general hospital setting with concurrent economic evaluation and a qualitative component. Potential participants are those admitted to hospital with a diagnosis likely to be responsive to addiction interventions who score equal to or more than 16 on the Alcohol Use Disorders Identification Test (AUDIT). The main purpose of this pilot study is to evaluate the acceptability of two sorts of interventions (healthy living related versus alcohol focused) to the participants and to assess the components and processes of the design. Qualitative research will be undertaken to explore acceptability and the impact of the approach, assessment, recruitment and intervention on trial participants and non-participants. The effectiveness of the two treatments will be compared at 6 months using AUDIT scores as the primary outcome measure. There will be additional economic, qualitative and secondary outcome measurements. DISCUSSION: Development of the study was a collaboration between academics, commissioners and clinicians in general hospital and addiction services, made possible by the Collaboration in Leadership in Applied Health Research and Care (CLAHRC) program of research. CLAHRC was a necessary vehicle for overcoming the barriers to answering an important NHS question--how better to engage problem drinkers in a hospital setting. TRIAL REGISTRATION: ISRCTN47728072.

A systematic review of substance misuse assessment packages.

ISSUES: Health-care systems globally are moving away from process measures of performance to payments for outcomes achieved. It follows that there is a need for a selection of proven quality tools that are suitable for undertaking comprehensive assessments and outcomes assessments. This review aimed to identify and evaluate existing comprehensive assessment packages. The work is part of a national program in the UK, Collaborations in Leadership of Applied Health Research and Care. APPROACH: Systematic searches were carried out across major databases to identify instruments designed to assess substance misuse. For those instruments identified, searches were carried out using the Cochrane Library, Embase, Ovid MEDLINE(®) and PsychINFO to identify articles reporting psychometric data. KEY FINDINGS: From 595 instruments, six met the inclusion criteria: Addiction Severity Index; Chemical Use, Abuse and Dependence Scale; Form 90; Maudsley Addiction Profile; Measurements in the Addictions for Triage and Evaluation; and Substance Abuse Outcomes Module. The most common reasons for exclusion were that instruments were: (i) designed for a specific substance (239); (ii) not designed for use in addiction settings (136); (iii) not providing comprehensive assessment (89); and (iv) not suitable as an outcome measure (20). IMPLICATIONS: The six packages are very different and suited to different uses. No package had adequate evaluation of their properties and so the emphasis should be on refining a small number of tools with very general application rather than creating new ones. An alternative to using 'off-the-shelf' packages is to create bespoke packages from well-validated, single-construct scales. [

Initial preference for drinking goal in the treatment of alcohol problems: I. Baseline differences between abstinence and non-abstinence groups.

AIMS: To compare baseline characteristics of clients initially preferring abstinence with those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (UKATT) and to identify predictors of goal preference from client characteristics present before the preference was stated. METHODS: From discussions with clients entering the trial (N = 742), screeners noted whether clients were aiming for abstinence 'probably yes' or 'probably no'. Differences between the two groups thus formed were explored by univariate comparisons among client characteristics recorded at baseline assessment and by logistic regression analysis with pre-existing characteristics as independent variables. RESULTS: Across all UKATT sites, 54.3% of clients expressed a preference for abstinence and 45.7% for non-abstinence. In univariate comparisons, clients preferring abstinence were significantly (P < 0.01) more likely to: (i) be female, (ii) be unemployed, (iii) report drinking more heavily but less frequently, (iv) have been detoxified in the 2 weeks prior to assessment, (v) report more alcohol problems, (vi) be in the action stage of change, (vii) report greater negative expectancies of drinking, (viii) report greater mental and physical ill-health, (ix) report less social support for drinking and (x) be more confident of their ability to resist heavy drinking in tempting situations. In the logistic regression model, the strongest predictors of goal preference were gender, drinking pattern, recent detoxification and social support for drinking. CONCLUSION: The implications of these findings for service delivery are best considered in conjunction with findings from a companion paper reporting treatment outcomes associated with each goal preference.

Initial preference for drinking goal in the treatment of alcohol problems: II. Treatment outcomes.

AIMS: To compare treatment outcomes between clients preferring abstinence and those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (the United Kingdom Alcohol Treatment Trial) and to interpret any differential outcome in light of baseline differences between goal preference groups outlined in an accompanying paper. METHODS: Outcomes at 3 and 12 months' follow-up were recorded both in categorical terms (abstinence/non-problem drinking/much improved/somewhat improved/same/worse) and on continuous measures (percent days abstinent, drinks per drinking day/dependence score). RESULTS: Clients initially stating a preference for abstinence showed a better outcome than those stating a preference for non-abstinence. This superior outcome was clearer at 3 months' follow-up but still evident at 12 months' follow-up. The better outcome consisted almost entirely in a greater frequency of abstinent days, with only a modest benefit in drinking intensity for goal abstainers that disappeared when baseline covariates of goal preference were controlled for. Type of successful outcome (abstinence/non-problem drinking) was related to initial goal preference, with clients preferring abstinence more likely to obtain an abstinent outcome and those preferring non-abstinence a non-problem drinking outcome. CONCLUSION: The client's personal drinking goals should be discussed in assessment at treatment entry and as a basis for negotiation. Clinicians should be prepared to identify and support goal change as an unexceptional part of the treatment process that need not jeopardize good outcome.

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.

BACKGROUND: There 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/DESIGN: The 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. DISCUSSION: The 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 REGISTRATION: ISRCTN52557360.

A comparison of buprenorphine and lofexidine for community opiate detoxification: results from a randomized controlled trial.

OBJECTIVE: To investigate whether a buprenorphine opiate detoxification regimen can be considered to be at least as clinically effective as a lofexidine regimen. DESIGN: An open-label randomized controlled trial (RCT) using a non-inferiority approach. Non-inferiority is demonstrated if, within a 95% confidence interval, buprenorphine performs within a preset tolerance limit of clinically acceptable difference in outcomes and completion rates between the two treatments. METHODS: Individuals ready for heroin detoxification were given information about the trial and invited to participate. Consenting participants (n = 210) were then randomized to one of the two treatments. Detoxification was undertaken in a specialist out-patient clinic according to predefined protocols. The primary outcome was whether or not an individual completed the detoxification. Abstinence at 1-month follow-up was used as a secondary outcome measure. Additional secondary outcome measures were substance use, dependence, psychological health, social satisfaction, and treatment satisfaction. Data were also collected for individuals who declined randomization and instead chose their treatment (n = 271). RESULTS: A total of 46% of those on lofexidine and 65% of those on buprenorphine completed detoxification. Of these, 35.7% of the lofexidine and 45.9% of the buprenorphine groups reported abstinence at 1 month. Of those not completing detoxification abstinence was reported at 27.5% and 29.0%, respectively; 271 individuals who opted not to be allocated randomly and instead chose one of the two treatments produced similar results CONCLUSIONS: Buprenorphine is at least as effective as lofexidine detoxification treatment. Whether or not individuals were randomized to, or chose, a treatment appeared not to affect the study's outcome.

Changes to methadone clearance during pregnancy.

OBJECTIVE: Measurement of plasma methadone concentration to investigate the rate of clearance of methadone prescribed for heroin dependence in the first, second and third trimesters of pregnancy. A secondary objective was to evaluate the outcome of pregnancy. METHODS: Longitudinal within subject study of nine pregnant opioid dependent subjects prescribed methadone at the Leeds Addiction Unit, an outpatient community based treatment centre. Plasma concentration versus time data for methadone was collected during each trimester and post-partum for our subjects. Data was available for the first and second trimesters for 4/9 cases. All but one of the subjects provided data during the third trimester and data post-partum was collected from three respondents. Measurements of methadone levels in plasma were carried out using high performance liquid chromatography (HPLC). RESULTS: Trough mean plasma methadone concentrations reduced as the pregnancies progressed from 0.12 mg/L (first trimester) to 0.07 mg/L (third trimester). The weight-adjusted clearance rates gradually increased from a mean of 0.17 to 0.21 L/hr/kg during pregnancy, although patterns differed substantially between the nine women. An assessment of relative clearance of methadone using two patients for whom we have had all three CL values (trimester 1-3) demonstrated notable change of CL (P = 0.056) over time. Eight of our subjects delivered (3 males), within two weeks of their due date the ninth (male) was premature (21 days). The mean length of gestation was 39.7 weeks (SD = 10 days) and none of the neonates met criterion for 'low birth weight' mean = 3094, SD = 368 g). Five neonates spent time (0.5-28 days) in a special care baby unit (SCUBU) and 4 of these displayed signs of methadone withdrawal. CONCLUSIONS: General Practitioners and hospital doctors should recognise the significant benefits of prescribing methadone for heroin-dependent women during pregnancy. We recommend that if a pregnant opioid user complains of methadone withdrawal symptoms (i.e. that the methadone dose does not "hold" them) the prescribing clinician takes this observation seriously and considers a more detailed assessment. Further work on key factors undergoing changes during pregnancy accounting for differences in methadone metabolism in the mother, fetus and neonate are required.