Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT.

Background: Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed. Objectives: To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption. Design: Multicentre, three-arm, parallel-group, randomised controlled clinical trial. Setting: Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands). Participants: Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate. Interventions: (1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation. Main outcome measures: Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule. Results: Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to -6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to -2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported. Limitations: The trial's primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted. Conclusions: Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate. Future work: Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence. Trial registration: This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.

Many people who are trying to stop drinking alcohol can find it difficult to remain alcohol free. There is a medication called acamprosate (Campral) that can reduce cravings thereby increasing the likelihood of abstinence. However, some people have trouble taking the right amount of acamprosate tablets needed every day at the right time, preferably at mealtimes. This means the medication is not as effective. We have tested some new ways to help support people taking acamprosate. We tested three different strategies to find the best way to support people taking acamprosate. We recruited 739 people aged 18 and over who were receiving alcohol treatment to stop drinking and were taking acamprosate. We randomly allocated these people to three groups. The first was Standard Support, the usual support people receive when taking acamprosate. The second group received Standard Support plus Medication Management. This consisted of 12 telephone calls over 6 months with a trained pharmacist to discuss the importance of taking the right amount of the medication, how the medication works and strategies to help people take the medication correctly. The third group received Standard Support, Medication Management and Contingency Management. This involved giving people shopping vouchers for participating with Medication Management calls. The maximum value of vouchers per person was £120. People who were in the group receiving Medication Management and Contingency Management took a greater number of acamprosate tablets. We also found that Medication Management plus Contingency Management was more cost-effective; there were greater gains in health with a smaller cost per person compared to Standard Support alone. This shows that there is likely to be a benefit to patients of Medication Management plus Contingency Management for supporting people taking acamprosate.

The impact of family interventions on communication in the context of anxiety and depression in those aged 14-24 years: systematic review of randomised control trials.

BACKGROUND: The ability to communicate is integral to all human relationships. Previous research has specifically highlighted communication within families as both a risk and protective factor for anxiety disorders and/or depression. Yet, there is limited understanding about whether communication is amenable to intervention in the context of adolescent psychopathology, and whether doing so improves outcomes. AIMS: The aim of this systematic review was to determine in which contexts and for whom does addressing communication in families appear to work, not work and why? METHOD: We pre-registered our systematic review with PROSPERO (identifier CRD42022298719), followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance and assessed study quality with the Risk of Bias 2 tool. RESULTS: Seven randomised controlled trials were identified from a systematic search of the literature. There was significant heterogeneity in the features of communication that were measured across these studies. There were mixed findings regarding whether family-focused interventions led to improvements in communication. Although there was limited evidence that family-focused interventions led to improvements in communication relative to interventions without a family-focused component, we discuss these findings in the context of the significant limitations in the studies reviewed. CONCLUSIONS: We conclude that further research is required to assess the efficacy of family-focused interventions for improving communication in the context of anxiety and depression in those aged 14-24 years.

Prolonged Benzodiazepine Levels Following Withdrawal in Alcohol Dependence.

OBJECTIVE: This article presents the benzodiazepine concentrations in urine samples from participants undergoing alcohol withdrawal in a Phase 4 "Proof of Concept" double-blind, randomized, controlled clinical trial. Chlordiazepoxide was prescribed to all participants "as needed" during the first 2 weeks only of alcohol withdrawal, to prevent serious consequences such as seizures. The trial examined effects of either mifepristone or placebo on the primary trial outcomes, which included cognitive function tests at 3 weeks and 4 weeks after the cessation of drinking. Because benzodiazepines are known to affect memory, urine benzodiazepine concentrations were measured before cognitive testing. METHOD: Urine samples were collected from participants immediately before each cognitive testing session, and the concentrations of unconjugated benzodiazepines (i.e., compounds active at benzodiazepine receptors) were measured by standard assay, using mass spectrometry. RESULTS: The urine benzodiazepine measurements showed clearly that amounts of active benzodiazepine metabolites were present during the third and fourth weeks after the cessation of drinking that were as high as or higher than those seen after therapeutic dosing. CONCLUSIONS: The urinary benzodiazepine concentrations demonstrated that residual active benzodiazepine compounds can be present up to 2 weeks after the last ingestion. This could affect the results of cognitive testing in people with alcohol dependence undergoing detoxification.

The clustering of physical health conditions and associations with co-occurring mental health problems and problematic alcohol use: a cross-sectional study.

BACKGROUND: There is strong evidence for the co-occurrence of mental health conditions and alcohol problems, yet physical health outcomes among this group are not well characterised. This study aimed to identify clusters of physical health conditions and their associations with mental health and problematic alcohol use in England's general population. METHODS: Cross-sectional analysis of the 2014 Adult Psychiatric Morbidity Survey (N = 7546) was conducted. The survey used standardised measures of problematic alcohol use and mental health conditions, including the Alcohol Use Disorders Identification Test (AUDIT) and the Clinical Interview Schedule-Revised. Participants self-reported any lifetime physical health conditions. Latent class analysis considered 12 common physical illnesses to identify clusters of multimorbidity. Multinomial logistic regression (adjusting for age, gender, ethnicity, education, and occupational grade) was used to explore associations between mental health, hazardous drinking (AUDIT 8 +), and co-occurring physical illnesses. RESULTS: Five clusters were identified with statistically distinct and clinically meaningful disease patterns: 'Physically Healthy' (76.62%), 'Emerging Multimorbidity' (3.12%), 'Hypertension & Arthritis' (14.28%), 'Digestive & Bowel Problems'' (3.17%), and 'Complex Multimorbidity' (2.8%). Having a mental health problem was associated with increased odds of 'Digestive & Bowel Problems' (adjusted multinomial odds ratio (AMOR) = 1.58; 95% CI [1.15-2.17]) and 'Complex Multimorbidity' (AMOR = 2.02; 95% CI [1.49-2.74]). Individuals with co-occurring mental health conditions and problematic alcohol use also had higher odds of 'Digestive & Bowel Problems' (AMOR = 2.64; 95% CI [1.68-4.15]) and 'Complex Multimorbidity' (AMOR = 2.62; 95% CI [1.61-4.23]). CONCLUSIONS: Individuals with a mental health condition concurrent with problematic alcohol use experience a greater burden of physical illnesses, highlighting the need for timely treatment which is likely to include better integration of alcohol and mental health services.

Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

AIMS: To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal. METHODS: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively. RESULTS: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence. CONCLUSION: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way.

Effectiveness and cost-effectiveness of face-to-face and electronic brief interventions versus screening alone to reduce alcohol consumption among high-risk adolescents presenting to emergency departments: three-arm pragmatic randomized trial (SIPS Junior high risk trial).

BACKGROUND AND AIMS: Alcohol use increases throughout adolescence. Emergency department (ED) attendance is an opportunity for alcohol screening and brief intervention (ASBI), which is effective for adults. This trial evaluated the effectiveness and cost-effectiveness of ASBI compared with screening alone (SA) in high-risk adolescents. DESIGN, SETTING AND PARTICIPANTS: Multi-centre, three-group, single-blind, individually randomized trial with follow-ups after 6 and 12 months in 10 ED settings in England. From October 2014 to May 2015 we screened 3327 adolescents aged 14 to 18 years, of whom 756 (22.7%) scored at least 3 on the Alcohol Use Disorders Identification Test: consumption (AUDIT-C) and consented to participate in this trial. Mean age was 16.1 years; 50.2% were female and 84.9% were white. INTERVENTIONS: Interventions were personalized feedback and brief advice (PFBA), personalized feedback plus electronic brief intervention (eBI) and SA. MEASURES: The primary outcome was the weekly alcohol consumed in standard UK units (8 g ethanol) at 12 months post-randomization, derived from extended AUDIT-C. Economic outcomes included quality of life and service use, from perspectives of both the National Health Service and personal social services (NHS&PSS) and society. FINDINGS: At 12 months, mean weekly consumption was 2.99 [95% confidence interval (CI) = 2.38-3.70] standard units for the SA group, 3.56 (95% CI = 2.90, 4.32) for PFBA and 3.18 (95% CI = 2.50, 3.97) for eBI, showing no significant differences. The PFBA group consumed mean 0.57 (-0.36, 1.70) units more than SA; and eBIs consumed 0.19 (-0.71, 1.30) more. Bayes factors suggested lack of effectiveness explained non-significance. From the NHS&PSS perspective, economic analysis showed that PFBA and eBI were not cost-effective compared with SA: PFBA yielded incremental cost-effectiveness ratio of £6213 (-£736 843, £812 884), with the intervention having 54% probability of being cost-effective compared with SA at the £20 000 WTP threshold. CONCLUSIONS: In emergency departments in England, neither personalized feedback and brief advice nor personalized feedback plus electronic brief intervention showed evidence of being effective or cost-effective when compared with screening alone in reducing alcohol consumption among adolescents.

The rates and measurement of adherence to acamprosate in randomised controlled clinical trials: A systematic review.

AIM: The current research aims to systematically review the rates of adherence reported in randomised controlled clinical trials of acamprosate. It also sought to determine the reliability of the adherence monitoring and measurement methods used in these trials. METHODS: The protocol for this review was pre-registered (PROSPERO: CRD42021230011). A search of the literature was conducted using OVID MEDLINE, Embase and PsycINFO from database inception to January 2021. Randomised controlled trials with a minimum sample size of 10 per treatment arm that compared the efficacy of acamprosate with placebo or other active medication in adults with a diagnosis of alcohol dependence were included. Data on rates of adherence, methods of measurement and monitoring of adherence was extracted from eligible studies independently in duplicate by two reviewers. A weighted mean adherence rate was calculated. The reliability of adherence monitoring methods was determined by calculating an adherence-assurance score based on the adherence monitoring method used. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: Fifteen studies met the eligibility criteria involving 4,450 participants (2,480 participants in the placebo arms). A mean adherence rate of 88% (54.2-95.0%) was reported across studies that reported the percentage of medication taken. A mean adherence rate of 84.9% (56.4-91.3%) was reported for trials that reported the percentage of participants taking more than 80% of medication prescribed. There is low confidence in the methods used to monitor adherence with all clinical trials having a low adherence-assurance rating. Risk of bias was judged to be high for all included studies. CONCLUSIONS: Adherence to acamprosate in clinical trials can be poor with low confidence in the methods used to measure it. Adherence rates therefore might not be accurate, which has implications for determining the efficacy of acamprosate.

Rethinking the course of psychotic disorders: modelling long-term symptom trajectories.

BACKGROUND: The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach. METHOD: AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time. RESULTS: We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory. CONCLUSION: Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.

The correlates and extent of prescribing of medications for alcohol relapse prevention in England.

AIMS: To determine the pattern and extent of prescribing of medications for alcohol relapse prevention (ARP) in England. DESIGN: Cross-sectional. SETTING: Specialist drug and alcohol treatment providers in England reporting to the National Drug Treatment Monitoring System. PARTICIPANTS: Service users aged 18+, with alcohol the primary substance of dependence, completing a treatment journey between April 2013 and March 2016 (n = 188 152). MEASUREMENTS: Prescription of medications for ARP during a treatment journey. Data on service users' demographics, treatment and clinical characteristics were extracted. FINDINGS: The rate of prescribing medications for ARP was 2.1% in 2013/14, 6.8% in 2014/15 and 7.8% in 2015/16. A greater likelihood of prescription was associated with treatment journey year [2014/15; adjusted odds ratio (aOR) = 3.269, 95% confidence intervals (CI) = 3.044-3.510, 2015/16; aOR = 3.823, CI = 3.560-4.106], age (25-34; aOR = 1.622, CI = 1.380-1.907, 35-54; aOR = 1.901, CI = 1.628-2.220 or 55+; aOR = 1.700, CI = 1.446-1.999), female gender (aOR = 1.129, CI = 1.077-1.184), white ethnicity (aOR = 1.219, CI = 1.077-1.380), regional prevalence of alcohol dependence (middle rate; aOR = 1.121, CI = 1.024-1.228), severity of alcohol dependence (moderate dependence without complex needs; aOR = 1.329, CI = 1.244-1.419, severe dependence without complex needs; aOR = 1.308, CI = 1.188-1.441, moderate/severe dependence with complex needs; aOR = 1.131, CI = 1.020-1.255), treatment setting (inpatient; aOR = 10.512, CI = 9.950-11.104, primary care; aOR = 2.264, CI = 2.050-2.500, residential; aOR = 3.216, CI = 2.807-3.685), prior treatment for alcohol dependence (aOR = 1.242, CI = 1.183-1.304), longer treatment journey (aOR = 1.002, CI = 1.002-1.002), more drinking days in the prior 28 days (aOR = 1.021, CI = 1.018-1.024) and drinking a higher number of alcohol units in the prior 28 days (aOR = 1.002 CI = 1.001-1.004). Living in a region of England with the lowest alcohol prevalence was associated with a lower likelihood of prescription of medication for aRP (AOR = 0.491, CI = 0.436-0.552). CONCLUSIONS: In England, medications for alcohol relapse prevention are rarely prescribed (e.g. 7.8% in 2015/16) and those prescriptions appear to be associated with specific service user demographics, treatment and clinical characteristics.

Brief interventions to prevent excessive alcohol use in adolescents at low-risk presenting to Emergency Departments: Three-arm, randomised trial of effectiveness and cost-effectiveness.

BACKGROUND: Alcohol consumption and related harm increase rapidly from the age of 12 years. We evaluated whether alcohol screening and brief intervention is effective and cost-effective in delaying hazardous or harmful drinking amongst low-risk or abstaining adolescents attending Emergency Departments (EDs). METHODS: This ten-centre, three-arm, parallel-group, single-blind, pragmatic, individually randomised trial screened ED attenders aged between 14 and 17 years for alcohol consumption. We sampled at random one third of those scoring at most 2 on AUDIT-C who had access to the internet and, if aged under 16, were Gillick competent or had informed consent from parent or guardian. We randomised them between: screening only (control intervention); one session of face-to-face Personalised Feedback and Brief Advice (PFBA); and PFBA plus an electronic brief intervention (eBI) on smartphone or web. We conducted follow-up after six and 12 months. The principal outcomes were alcohol consumed over the 3 months before 12-month follow up, measured by AUDIT-C; and quality-adjusted life-years. FINDINGS: Between October 2014 and May 2015, we approached 5,016 eligible patients of whom 3,326 consented to be screened and participate in the trial; 2,571 of these were low-risk drinkers or abstainers, consuming an average 0.14 units per week. We randomised: 304 to screening only; 285 to PFBA; and 294 to PFBA and eBI. We found no significant difference between groups, notably in weekly alcohol consumption: those receiving screening only drank 0.10 units (95% confidence interval 0.05 to 0.18); PFBA 0.12 (0.06 to 0.21); PFBA and eBI 0.10 (0.05 to 0.19). INTERPRETATION: While drinking levels remained low in this population, this trial found no evidence that PFBA with or without eBI was more effective than screening alone in reducing or delaying alcohol consumption.

Diagnostic stability and outcome after first episode psychosis.

BACKGROUND: Individuals diagnosed with schizophrenia are often assigned other psychiatric diagnoses during their lives. The significance of changing diagnosis has not been widely studied. AIMS: Our aim was to examine the association between diagnostic change and later outcome. METHODS: Individuals' diagnostic history, clinical and social outcomes were extracted from the AESOP-10 study, a 10-year follow-up of first episode psychosis cases. The association between outcome and different patterns of diagnosis over time were assessed using linear or logistic regression. RESULTS: Individuals always diagnosed with schizophrenia (n = 136) had worse clinical and social outcomes at follow-up than those never diagnosed with schizophrenia (n = 163), being more likely to be symptomatic, unemployed, single, and socially isolated. There was no difference in outcome between individuals always diagnosed with schizophrenia and those changing to a diagnosis of schizophrenia (n = 60), and no difference in outcome between individuals never diagnosed with schizophrenia, and those changing from a diagnosis of schizophrenia (n = 44). CONCLUSIONS: Individuals always and never diagnosed with schizophrenia had different outcomes. In cases of diagnostic instability participants had similar outcomes to those always assigned the diagnosis they changed to irrespective of initial diagnosis.

Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study.

Minor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches.

Double-blind, placebo-controlled trial of mifepristone on cognition and depression in alcohol dependence.

BACKGROUND: Alcohol dependence is a significant issue contributing to disease burden. Changes in cortisol concentrations during alcohol withdrawal are associated with cognitive deficits and symptoms of depression. Current treatments are only successful for a small proportion of people and do not target cognitive deficits and symptoms of depression experienced by those who are alcohol dependent. The aim of this research is to determine the potential efficacy of mifepristone, a type II glucocorticoid receptor antagonist, to prevent symptoms of depression and cognitive deficits following alcohol detoxification. METHODS: This was a phase 2 therapeutic use trial. It was a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo treatment. The trial aimed to recruit 120 participants who met the inclusion criteria: (1) male, (2) aged 18-60 years inclusive, and (3) alcohol dependent for 5 or more years. Participants were randomised to 600 mg a day mifepristone (200 mg morning, afternoon, and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Primary outcome measures were cognitive function (measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB)) and symptoms of depression (measured using the Beck Depression Inventory (BDI)) at 4 weeks post-randomisation. RESULTS: Difficulties recruiting participants due to significant changes in the provision of inpatient care for alcohol dependence resulted in only 27 participants recruited to the trial, with data available for 21 participants. Fourteen participants were randomised to receive mifepristone and 13 to receive placebo. CONCLUSION: Larger trials would be needed to draw conclusions about the efficacy of mifepristone. TRIAL REGISTRATION: ISRCTN registry ISRCTN54001953 . Registered on 29 September 2011.

Symptom remission at 12-weeks strongly predicts long-term recovery from the first episode of psychosis.

BACKGROUND: To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis. METHODS: AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up. RESULTS: At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60-7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02-7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23-6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25-8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61-41.42). CONCLUSIONS: Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Opportunistic screening for alcohol use problems in adolescents attending emergency departments: an evaluation of screening tools.

OBJECTIVE: To estimate and compare the optimal cut-off score of Alcohol Use Disorders Identification Test (AUDIT) and AUDIT-C in identifying at-risk alcohol consumption, heavy episodic alcohol use, ICD-10 alcohol abuse and alcohol dependence in adolescents attending ED in England. DESIGN: Opportunistic cross-sectional survey. SETTING: 10 emergency departments across England. PARTICIPANTS: Adolescents (n = 5377) aged between their 10th and 18th birthday who attended emergency departments between December 2012 and May 2013. MEASURES: Scores on the AUDIT and AUDIT-C. At-risk alcohol consumption and monthly episodic alcohol consumption in the past 3 months were derived using the time-line follow back method. Alcohol abuse and alcohol dependence was assessed in accordance with ICD-10 criteria using the MINI-KID. FINDINGS: AUDIT-C with a score of 3 was more effective for at-risk alcohol use (AUC 0.81; sensitivity 87%, specificity 97%), heavy episodic use (0.84; 76%, 98%) and alcohol abuse (0.98; 91%, 90%). AUDIT with a score of 7 was more effective in identifying alcohol dependence (0.92; 96%, 94%). CONCLUSIONS: The 3-item AUDIT-C is more effective than AUDIT in screening adolescents for at-risk alcohol use, heavy episodic alcohol use and alcohol abuse. AUDIT is more effective than AUDIT-C for the identification of alcohol dependence.

Neuropsychological function at first episode in treatment-resistant psychosis: findings from the ÆSOP-10 study.

BACKGROUND: Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis. METHODS: We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up. RESULTS: Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = -2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = -2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01-0.001) and those born outside the UK (p values<0.05). CONCLUSIONS: Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable - at a group level - at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

The Effect of Brief Interventions for Alcohol Among People with Comorbid Mental Health Conditions: A Systematic Review of Randomized Trials and Narrative Synthesis.

AIMS: To review the evidence on the effect of brief interventions (BIs) for alcohol among adults with risky alcohol consumption and comorbid mental health conditions. METHODS: A systematic review of randomized controlled trials (RCTs) published before May 2016 was undertaken and reported according to PRISMA guidelines. The findings were combined in a narrative synthesis. The risk of bias was assessed for included trials. RESULTS: Seventeen RCTs were included in the review and narrative synthesis: 11 in common mental health problems, and 6 in severe mental illness. There was considerable heterogeneity in study populations, BI delivery mode and intensity, outcome measures and risk of bias. Where BI was compared with a minimally active control, BI was associated with a significant reduction in alcohol consumption in four out of nine RCTs in common mental disorders and two out of five RCTs in severe mental illness. Where BI was compared with active comparator groups (such as motivational interviewing or cognitive behavioural therapy), findings were also mixed. Differences in the findings may be partly due to differences in study design, such as the intensity of BI and possibly the risk of bias. CONCLUSIONS: Overall, the evidence is mixed regarding the effects of alcohol BI in participants with comorbid mental health conditions. Future well-designed research is required to answer this question more definitively.

Variance in the Efficacy of Brief Interventions to Reduce Hazardous and Harmful Alcohol Consumption Between Injury and Noninjury Patients in Emergency Departments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

STUDY OBJECTIVE: We adopt a comparative framework to measure the extent to which variance in the efficacy of alcohol brief interventions to reduce hazardous and harmful drinking at less than or equal to 5-, 6-, and 12-month follow-up in emergency department settings can be determined by differences between study populations (targeted injury and noninjury specific). METHODS: A systematic review and meta-analysis of randomized controlled trials published before September 2016 was undertaken. Twenty-three high-quality and methodologically similar randomized controlled trials were eligible, with a total number of 15,173 participants included. Primary outcome measure was efficacy of brief intervention compared with a control group in reducing quantity of alcohol consumed. An inverse variance model was applied to measure the effect of treatment in standard mean differences for brief intervention and control groups. RESULTS: At 6-month follow-up, an effect in favor of brief intervention over control was identified for targeted injury studies (standardized mean difference=-0.10; 95% confidence interval [CI] -0.17 to -0.02; I2=0%). For pooled noninjury-specific studies, small benefits of brief intervention were evident at less than or equal to 5-month follow-up (standardized mean difference=-0.15; 95% CI -0.24 to -0.07; I2=0%), at 6-month follow-up (standardized mean difference=-0.08; 95% CI -0.14 to -0.01; I2=1%), and at 12-month follow-up (standardized mean difference=-0.08; 95% CI -0.15 to -0.01; I2=0%). CONCLUSION: Meta-analysis identified noninjury-specific studies as associated with better response to brief intervention than targeted injury studies. However, the inclusion of injured patients with noninjured ones in the experimental and control groups of noninjury-specific studies limited the interpretation of this finding.