The Effect of Methylphenidate on Cognition in Patients with Comorbid Attention Deficit/Hyperactivity Disorder and Amphetamine Use Disorder: An Exploratory Single-Blinded within-Subject Study.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) with co-occurring substance use disorder (SUD) is associated with poor treatment outcomes. Two randomized controlled trials, utilizing robust doses of stimulants, demonstrated a significant effect on treatment outcomes in patients with ADHD/SUD. This study aimed to investigate differences in executive functioning and explore the dose-dependent effect of OROS-methylphenidate (MPH) in patients with comorbid ADHD and amphetamine use disorder (ADHD+AMPH) and patients with ADHD only. METHODS: Three groups (ADHD+AMPH, ADHD only, and healthy controls) were assessed repeatedly with a neuropsychological test battery. An exploratory within-subject single-blinded design was employed where the ADHD only group received a maximum dose of 72 mg OROS-MPH, the ADHD+AMPH group a maximum dose of 180 mg, whereas the healthy subjects did not receive any study medication. Both ADHD groups received the same dose titration up to 72 mg OROS-MPH. RESULTS: The ADHD+AMPH group demonstrated a significantly poorer motor inhibition and spatial working memory and reported more severe ADHD symptoms compared to the ADHD only group. 180 mg OROS-MPH was associated with a significant improvement in executive functioning in the dual diagnosis group. However, the exploratory study design and recruitment issues do not allow for any conclusion to be drawn regarding the effect of 180 mg OROS-MPH. CONCLUSION: Patients with ADHD+AMPH present with more severe neurocognitive deficits compared to ADHD only. The effect of 180 mg OROS-MPH on cognition in patients with ADHD+AMPH was inconclusive. Future studies should consider recruitment issues and high drop-out rates in this study population.

Meta-analysis of pharmacogenetic clinical decision support systems for the treatment of major depressive disorder.

The study aimed to conduct a meta-analysis of studies comparing pharmacogenetically guided dosing of antidepressants with empiric standard of care. Publications referring to genotype-guided antidepressant therapy were identified via PubMed, Google Scholar, Scopus, Web of Science, Embase, and Cochrane databases from the inception of the databases to 2021. In addition, bibliographies of all articles were manually searched for additional references not identified in primary searches. Studies comparing clinical outcomes between two groups of patients who received antidepressant treatment were included in meta-analysis. Analysis of the data revealed statistically significant differences between the experimental group receiving pharmacogenetically guided dosing and the empirically treated controls. Specifically, genotype-guided treatment significantly improved response and remission of patients after both eight and twelve weeks of therapy, whereas no effect on the development of adverse drug reactions was observed. This meta-analysis indicates that the use of preemptive genotyping to guide dosing of antidepressants might increase treatment efficacy.

Alcohol as a risk factor for mortality in liver transplant patients in Sweden.

OBJECTIVES: Liver transplantation (LT) is the only available cure for end-stage liver disease and one of the best treatment options for hepatocellular carcinomas (HCC). Patients with known alcohol-associated cirrhosis (AC) are routinely assessed for alcohol dependence or abuse before LT. Patients with other liver diseases than AC may consume alcohol both before and after LT. The aim of this study was to assess the effects of alcohol drinking before and after LT on patient and graft survival regardless of the etiology of liver disease. MATERIALS AND METHODS: Between April 2012 and December 2015, 200 LT-recipients were interviewed using the Lifetime Drinking History and the Addiction Severity Index questionnaire. Patients were categorized as having AC, n = 24, HCC and/or hepatitis C cirrhosis (HCV), n = 69 or other liver diseases, n = 107. Patients were monitored and interviewed by transplantation-independent staff for two years after LT with questions regarding their alcohol consumption. Patient and graft survival data were retrieved in October 2019. RESULTS: Patients with AC had an increased hazard ratio (HR) for death after LT (crude HR: 4.05, 95% CI: 1.07-15.33, p = 0.04) and for graft loss adjusted for age and gender (adjusted HR: 3.24, 95% CI 1.08-9.77, p = 0.04) compared to the other patients in the cohort. There was no significant effect of the volume of alcohol consumed before or after LT on graft loss or overall survival. CONCLUSION: Patients transplanted for AC have a worse prognosis, but we found no correlation between alcohol consumed before or after LT and graft or patient survival.

Impulsive choice in individuals with comorbid amphetamine use disorder and attention deficit-hyperactivity disorder.

BACKGROUND: Amphetamine use disorder (AMPH) and attention deficit-hyperactivity disorder (ADHD) often co-occur and are associated with poor treatment outcomes. Elevated impulsivity is a core feature in both disorders. Little is known however about the specific neurocognitive profile regarding different facets of impulsivity, and specifically impulsive choice, in comorbid populations. METHODS: Three groups (ADHD + AMPH, ADHD only and healthy controls (HC)) were assessed with self-reported impulsivity and cognitive tasks of impulsive choice, operationalized as delay aversion (DA) and reflection impulsivity. RESULTS: Twenty-nine participants with comorbid ADHD + AMPH, 25 participants with ADHD only and 116 HC completed screening, including self-rating scales, and cognitive testing. 20, 16 and 114 participants completed computerized cognitive tasks in the ADHD + AMPH group, ADHD group and HC group, respectively. The ADHD + AMPH group reported significantly higher motor, attentional and non-planning impulsiveness, and showed a significantly higher degree of impulsive choice, compared to both groups. There were no differences in task-related impulsiveness between ADHD only and HC. CONCLUSIONS: The current findings suggest that individuals with ADHD + AMPH have overall elevated levels of impulsivity compared to individuals with ADHD only. In addition, that ADHD + AMPH is specifically associated with impairments in task-related impulsive choice, which was not found in ADHD only compared to HC. The neurocognitive profile in this specific patient group may represent a need for more systematic screening within healthcare settings in order to develop effective and targeted treatment for comorbid patients. TRIAL REGISTRATION: EudraCT, 2012-004298-20.

Acute Alcoholic Hallucinosis: A Review.

Acute alcoholic hallucinosis is a psychotic disorder characterized by a predominance of auditory hallucinations with delusions and affective symptoms in the clinical picture. Classically, it develops as part of the alcohol withdrawal syndrome. The prevalence of acute alcoholic hallucinosis ranks second among alcohol-related psychoses after alcohol delirium. The study aimed to systematize the scientific data on the history of alcoholic hallucinosis, its pathogenesis, clinical presentation, and treatment approaches. A literature search was performed in PubMed, Scopus, Google Scholar, and eLibrary. The following words and combinations were used as search strings: (alcoholic hallucinosis OR alcoholic psychosis OR alcohol-related psychosis OR alcohol-induced psychosis OR alcohol-induced psychotic disorder OR complicated alcohol withdrawal syndrome) NOT (animal OR rat OR mouse). The relevant information concerning the history of acute alcoholic hallucinosis, its pathogenesis, clinical picture, and treatment approaches was systematized and summarized. This review presents relevant findings regarding acute alcoholic hallucinosis. Limitations of the review include the use of heterogeneous and mostly descriptive studies and studies on small cohorts of patients.

CYP3A4*22 and CYP3A5*3 impact efficacy and safety of diazepam in patients with alcohol withdrawal syndrome.

BACKGROUND: Diazepam is one of the most commonly prescribed pharmaceuticals for the treatment of alcohol withdrawal syndrome (AWS). However, diazepam sometimes is ineffective, and some patients experience dose-dependent adverse drug reactions (ADR). Previous studies have shown that diazepam metabolism involves the CYP3A4 and CYP3A5 isoenzymes, whose activity is highly variable between individuals, which may contribute to differences in clinical response. PURPOSE: The study aimed to investigate the effects of the genetic polymorphisms CYP3A4*22 and CYP3A5*3 on the efficacy and safety of diazepam in patients with AWS. MATERIALS AND METHODS: One hundred male AWS patients received 30 mg/day diazepam by intramuscular injections for 5 days. Genotyping for CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessments were performed using psychometric scales. RESULTS: Patients who carry CT and TT genotypes by polymorphic marker C > T intron 6 (rs35599367) of the CYP3A4 gene had a higher risk for ADR and demonstrated lower safety of diazepam therapy (p < 0.001; two-way ANOVA). CONCLUSION: These results suggest that genotyping for common CYP3A variants might have the potential to guide benzodiazepine withdrawal treatment.

Effect of alcohol use disorder family history on cognitive function.

BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits but little is known to what degree this is caused by genetically influenced traits, i.e. endophenotypes, present before the onset of the disorder. The aim of the current study was to investigate to what degree family history (FH) of AUD is associated with cognitive functions. METHODS: Case-control cross-sectional study at an outpatient addiction research clinic. Treatment-seeking AUD patients (n = 106) were compared to healthy controls (HC; n = 90), matched for age and sex. The HC group was further subdivided into AUD FH positive (FH+; n = 47) or negative (FH-; n = 39) based on the Family Tree Questionnaire. Participants underwent psychiatric and substance use assessments, completed the Barratt Impulsiveness Scale and performed a comprehensive battery of neuropsychological tests assessing response inhibition, decision making, attention, working memory, and emotional recognition. RESULTS: Compared to HC, AUD patients exhibited elevated self-rated impulsivity (p < 0.001; d = 0.62), as well as significantly poorer response inhibition (p = 0.001; d = 0.51), attention (p = 0.021; d = 0.38) and information gathering in decision making (p = 0.073; d = 0.34). Similar to AUD patients, FH+ individuals exhibited elevated self-rated impulsivity (p = 0.096; d = 0.46), and in addition significantly worse future planning capacity (p < 0.001; d = 0.76) and prolonged emotional recognition response time (p = 0.010; d = 0.60) compared to FH-, while no other significant differences were found between FH+ and FH-. CONCLUSIONS: Elevated impulsivity, poor performance in future planning and emotional processing speed may be potential cognitive endophenotypes in AUD. These cognitive domains represent putative targets for prevention strategies and treatment of AUD.

Mortality in adult children of parents with alcohol use disorder: a nationwide register study.

Research suggests that adult children of parents with harmful alcohol use are at increased risk for premature death. This national cohort study investigated mortality in adult children of parents with alcohol use disorder (AUD), adjusting for sociodemographic variables. The study used 1973 to 2018 data from Swedish national registers to compare mortality risk in children who had ≥ 1 parent with AUD (ICD-10 code F10 and its ICD-8 and ICD-9 equivalents) (n = 122,947) and those who did not (n = 2,298,532). A Cox regression model adjusted for year of birth, sex, parental education, and childhood loss of a parent was used. Before the age of 18 years, about 5% of children born in Sweden lived with ≥ 1 parent who had a clinical diagnosis of AUD. Overall mortality was higher in adult children of parents with AUD: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.71-1.82. Mortality remained elevated after adjustments for sociodemographic factors (HR 1.45, 95% CI 1.40-1.50). Children of parents with AUD had increased mortality from all investigated causes. The highest excess risk was for death from drug-related causes (excluding accidental poisonings) (HR 3.08, 95% CI 2.74-3.46). For most causes, mortality was higher if the mother had AUD than if the father had AUD. Patterns of mortality were similar in both sexes. This study provides evidence that parental AUD raises the risk of offspring mortality from preventable causes such as drug use, suicide (HR 2.16, 95% CI 1.98-2.36), accident (HR 2.00, 95% CI 1.87-2.13), and assault (HR 1.76, 95% CI 1.38-2.24).

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study.

INTRODUCTION: Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. METHODS: We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. RESULTS: There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. DISCUSSION/CONCLUSION: We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

Self-rated impulsivity in healthy individuals, substance use disorder and ADHD: psychometric properties of the Swedish Barratt impulsiveness scale.

BACKGROUND: Impulsivity is associated with several psychiatric disorders, including substance use disorders (SUD) and attention deficit hyperactivity disorder (ADHD). A widely used questionnaire to assess impulsivity is the Barratt Impulsiveness Scale (BIS), and the aim of the current study was to evaluate the psychometric properties of the Swedish version of the BIS (swe-BIS). METHODS: The original BIS was translated to Swedish and back-translated by an authorized translator. The swe-BIS was administered to healthy controls (n = 113), patients with alcohol use disorder (n = 97), amphetamine use disorder (n = 37) and attention deficit hyperactive disorder (ADHD; n = 26). A subset of subjects (n = 62) completed the swe-BIS twice within 1 week. Psychometric evaluation of the swe-BIS included assessment of different indices of reliability (internal consistency, test-retest and agreement) and validity (response processess, divergent and convergent). Confirmatory factor analyses (CFA) were performed to assess several indices of model fit in five different models based on previously suggested subscales. RESULTS: Cronbach's alpha for all swe-BIS items in the full sample was 0.89, ranging from 0.78-0.87 within the different subgroups. The Pearson test-retest correlation for total score was 0.78 (p < 0.001), with greater test-retest correlations within compared to across different subscales. The Bland-Altman plot indicated high level of agreement between test and retest. The healthy individuals had lower swe-BIS score compared to the patients (t(267.3) = - 8.6; p < 0.001), and the swe-BIS total score was also significantly different between each of the four participant groups (p < 0.01 for all group comparisons). Furthermore, swe-BIS had greater correlations with impulsivity related scales compared to non-impulsivity related scales. The CFA analyses indicated that while no suggested model showed an optimal fit, the best model fit indices was found for the 3-factor model. CONCLUSIONS: The swe-BIS was found to have good to excellent psychometric properties with respect to the assessed indices of reliability and validity, supporting use of the scale in clinical research in both healthy individuals and patients with SUD and ADHD.

[International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder]. / Internationale Konsenserklärung zu Screening, Diagnostik und Behandlung von Jugendlichen und Heranwachsenden mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung und gleichzeitigen Störungen durch Substanzgebrauch.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract. Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Family History of Alcohol Abuse Associated with Higher Impulsivity in Patients with Alcohol Use Disorder: A Multisite Study.

BACKGROUND: Alcohol use disorder (AUD) is to a high degree heritable, and in clinical practice it is common to assert presence of alcohol abuse family history (FH) in treatment-seeking AUD patients. Patients with AUD also exhibit cognitive deficits, including elevated impulsivity and impairments in executive functions (EF), but less is known regarding the relation between FH and these cognitive domains. The aim of the current study was to investigate if alcohol abuse FH in AUD patients is associated with a specific cognitive profile. METHODS: Patients with AUD (n = 197) from Sweden (n = 106) and Belgium (n = 91) were recruited. Self-rated impulsivity was assessed by the Barratt Impulsiveness Scale (BIS). EF assessed were response inhibition (stop signal task), attention (rapid visual processing task), and working memory (digit span). A series of linear regression models were run to explore the effect of FH on cognitive outcomes. RESULTS: A FH of alcohol abuse was associated with elevated score in self-rated impulsivity assessed by the BIS, with the greatest effect on the subscale of nonplanning. There was no statistically significant association between FH and any of the other neuropsychological task outcomes. CONCLUSION: Presence of alcohol abuse FH within AUD patients could be a marker of higher impulsivity, which may have clinical implications regarding diagnostic evaluation and treatment.

The International Collaboration on ADHD and Substance Abuse (ICASA): Mission, Results, and Future Activities.

BACKGROUND: The International Collaboration on ADHD and Substance Abuse (ICASA) is a network of 28 centers from 16 countries initiated to investigate the link between attention deficit-hyperactivity disorder (ADHD) and substance use disorder (SUD). In this article, we present the mission, the results of finished studies, and the current and future research projects of ICASA. METHODS: During the past 10 years, 3 cross-sectional studies were conducted: two International ADHD in Substance use disorders Prevalence (IASP-1 and IASP-2) studies, directed at the screening, diagnosis, and the prevalence of adult ADHD in treatment-seeking patients with SUD, and the Continuous performance test for ADHD in SUD Patients (CASP) study, testing a novel continuous performance test in SUD patients with and without adult ADHD. Recently, the prospective International Naturalistic Cohort Study of ADHD and Substance Use Disorders (INCAS) was initiated, directed at treatment provision and treatment outcome in SUD patients with adult ADHD. RESULTS: The IASP studies have shown that approximately 1 in 6 adult treatment-seeking SUD patients also have ADHD. In addition, those SUD patients with adult ADHD compared to SUD patients without ADHD report more childhood trauma exposure, slower infant development, greater problems controlling their temperament, and lower educational attainment. Comorbid patients also reported more risk-taking behavior, and a higher rate of other psychiatric disorders compared to SUD patients without ADHD. Screening, diagnosis, and treatment of this patient group are possible even before abstinence has been achieved. The results of the CASP study are reported separately in this special issue. CONCLUSIONS: The ICASA research to date has demonstrated a high prevalence of comorbid ADHD and SUD, associated with elevated rates of additional comorbidities and risk factors for adverse outcomes. More research is needed to find the best way to treat these patients, which is the main topic of the ongoing INCAS study.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder.

BACKGROUND: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. OBJECTIVE: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. METHOD: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. RESULTS: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. CONCLUSION: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

[Recommendations for the screening, diagnosis and treatment of patients with comorbid attention deficit hyperactivity- and substance use disorder].

Among patients with substance use disorders (SUD), adult attention deficit hyperactivity disorder (ADHD) is one of the most frequently co-occuring disorder. Those SUD patients with comorbid ADHD show earlier onset of substance use, more severe SUD and poor treatment outcomes. Therefore, early recognition of ADHD is highly rele - vant within this patient population. The results of available screening instruments may lay the foundation of timely ADHD diagnosis. Considering the integrated treatment of patients with a dual ADHD+SUD diagnosis, the applica tion of combined pharmaco- and psychotherapy is recommended. Based on the evidence-and consensus-based suggestions, prescription of long-acting methylphenidate, extended-release amphetamines and atomoxetine with up-titration might be the best choice in the treatment of patients who are either unresponsive to standard dose or characterized by therapy resistance. The main purpose of this manuscript is to establish a standing-ground for the effective screening, diagnosis and treatment of ADHD+SUD patients.

Alcohol and drug use prior to liver transplantation: more common than expected in patients with non-alcoholic liver disease.

Objective: Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease, acute liver failure or hepatocellular carcinoma (HCC). Patients with known alcoholic liver cirrhosis (ALC) are usually assessed by an addiction specialist, but patients with other liver diseases may also exhibit harmful drinking. This study aims to assess the drinking habits in LT-recipients with or without a diagnosis of ALC. Patients and methods: Between April 2012 and December 2015, 190 LT-recipients were interviewed using the Lifetime Drinking History (LDH) and the Addiction Severity Index (ASI). Patients were categorized according to their diagnoses: ALC (group A, n = 39), HCC or hepatitis C (group B, n = 56) or other liver diseases (group C, n = 95). Data were analysed using descriptive statistic methods. Results: Fifteen of 95 patients (15.8%) in group C - a cohort without suspected addiction problems - had either alcohol consumption or binge drinking within the upper quartile of the overall cohort. The aetiology of liver disease in this subgroup included mainly cholestatic and cryptogenic liver disease. Illicit drugs had been used by 35% of all patients. Cannabis and amphetamine were the most common drugs and had the longest duration of regular use. Conclusions: LT candidates without known alcohol or drug use may have a clinically significant consumption of alcohol and previous illicit drug use. Efforts should be put on identification of these patients during LT evaluation. The use of structured questionnaires such as the ASI and the LDH could facilitate detection of alcohol and drug problems.

Methylphenidate effects on processing speed in a clinical sample of adults with ADHD and substance use disorder: a pilot study.

BACKGROUND: Substance use disorders (SUDs) are common comorbidities of Attention Deficit Hyperactivity Disorder (ADHD). The most commonly prescribed medication for ADHD is methylphenidate. The clinical response to methylphenidate may be monitored against DSM-5 symptomatology, rating scales or interviews. AIMS: To evaluate the use of perceptual and cognitive processing speed measures to monitor methylphenidate effects in adults with ADHD and SUD. METHODS: A Quick Test of Cognitive Speed (AQT) monitored perceptual and cognitive processing speed in 28 adults with ADHD and SUD on treatment with methylphenidate before and after the morning dose. RESULTS: Twenty-six patients responded on AQT after the morning dose of methylphenidate. One-way ANOVA indicated significant treatment effects for color, form, and color-form combination naming, but not for shift cost values. Before the morning dose of methylphenidate, 92% were identified by cutoff time criteria for longer-than-normal processing times. After the morning dose of methylphenidate, 65% obtained color and form measures in the normal range for age peers. Only 35% obtained color-form processing measures in the normal range. Inter-individual response variability before medication intake was considerably larger than previously reported in studies of adults with ADHD only. CONCLUSION: Proportionally, fewer adults with ADHD and SUD exhibited normalization of processing speed than previously observed for adults with ADHD without SUD. A potential clinical implication of the present study is that the AQT test may be used as a tool for dose-adjustment of central stimulants in the treatment of adults with ADHD and SUD.

Benzodiazepine prescribing for children, adolescents, and young adults from 2006 through 2013: A total population register-linkage study.

BACKGROUND: Pharmacoepidemiological studies have long raised concerns on widespread use of benzodiazepines and benzodiazepine-related drugs (BZDs), in particular long-term use, among adults and the elderly. In contrast, evidence pertaining to the rates of BZD use at younger ages is still scarce, and the factors that influence BZD utilisation and shape the different prescribing patterns in youths remain largely unexplored. We examined the prevalence rates, relative changes in rates over time, and prescribing patterns for BZD dispensation in young people aged 0-24 years in Sweden during the period January 1, 2006-December 31, 2013, and explored demographic, clinical, pharmacological, and prescriber-related attributes of BZD prescribing in this group. METHODS AND FINDINGS: Through the linkage of 3 nationwide Swedish health and administrative registers, we collected data on 17,500 children (0-11 years), 15,039 adolescents (12-17 years), and 85,200 young adults (18-24 years) with at least 1 dispensed prescription for a BZD during 2006-2013, out of 3,726,818 Swedish inhabitants aged 0-24 years. Age-specific annual prevalence rates of BZD dispensations were adjusted for population growth, and relative changes in rates were calculated between 2006 and 2013. We analysed how BZD dispensation varied by sex, psychiatric morbidity and epilepsy, concurrent dispensation of psychotropic medication, type of dispensed BZD, and type of healthcare provider prescribing the BZD. Prescribing patterns were established in relation to duration (3 months, >3 to ≤6 months, or >6 months), dosage (<0.5 defined daily dosage [DDD]/day, ≥0.5 to <1.5 DDD/day, or ≥1.5 DDD/day), and "user category" ("regular users" [≥0.5 to <1.5 DDD/day for ≥1 year], "heavy users" [≥1.5 DDD/day for ≥1 year], or otherwise "occasional users"). Multinomial regression models were fitted to test associations between BZD prescribing patterns and individual characteristics of study participants. Between 2006 and 2013, the prevalence rate of BZD dispensation among individuals aged 0-24 years increased by 22% from 0.81 per 100 inhabitants to 0.99 per 100 inhabitants. This increase was mainly driven by a rise in the rate among young adults (+20%), with more modest increases in children (+3%) and adolescents (+7%). Within each age category, overall dispensation of BZD anxiolytics and clonazepam decreased over time, while dispensation of BZD hypnotics/sedatives, including Z-drugs, showed an increase between 2006 and 2013. Out of 117,739 study participants with dispensed BZD prescriptions, 65% initiated BZD prescriptions outside of psychiatric services (92% of children, 60% of adolescents, 60% of young adults), and 76% were dispensed other psychotropic drugs concurrently with a BZD (46% of children, 80% of adolescents, 81% of young adults). Nearly 30% of the participants were prescribed a BZD for longer than 6 months (18% of children, 31% of adolescents, 31% of young adults). A high dose prescription (≥1.5 DDD/day) and heavy use were detected in 2.6% and 1.7% of the participants, respectively. After controlling for potential confounding by demographic and clinical characteristics, the characteristics age above 11 years at the first BZD dispensation, lifetime psychiatric diagnosis or epilepsy, and concurrent dispensation of other psychotropic drugs were found to be associated with higher odds of being prescribed a BZD for longer than 6 months, high dose prescription, and heavy use. Male sex was associated with a higher likelihood of high dose prescription and heavy use, but not with being prescribed a BZD on a long-term basis (> 6 months). The study limitations included lack of information on actual consumption of the dispensed BZDs and unavailability of data on the indications for BZD prescriptions. CONCLUSIONS: The overall increase in prevalence rates of BZD dispensations during the study period and the unexpectedly high proportion of individuals who were prescribed a BZD on a long-term basis at a young age indicate a lack of congruence with international and national guidelines. These findings highlight the need for close monitoring of prescribing practices, particularly in non-psychiatric settings, in order to build an evidence base for safe and efficient BZD treatment in young persons.

Mentalization-Based Treatment for Concurrent Borderline Personality Disorder and Substance Use Disorder: A Randomized Controlled Feasibility Study.

AIMS: There is a scarcity of clinical trials on psychological treatments for concurrent borderline personality disorder (BPD) and substance use disorder (SUD). Mentalization-based treatment (MBT) have shown efficacy in several trials on BPD. The aim of the present study was to examine the feasibility and effectiveness of MBT for concurrent BPD and SUD. METHODS: Patients (n = 46) with concurrent BPD and SUD were randomized either to MBT in combination with SUD treatment (n = 24) or to SUD treatment alone (n = 22). Outcome was measured after 18 months using objective data, as well as interview and self-report measures. RESULTS: There was no significant difference between the groups on any outcome variable. No suicide attempts occurred in the MBT group in contrast to 4 suicide attempts that occurred in the control group - a difference that did not reach statistical significance (p = 0.06). A majority of the therapists did not show sufficient MBT adherence and quality. CONCLUSION: MBT for patients with concurrent BPD and SD does not appear to be harmful; on the other hand, it is possibly helpful in reducing the risk involved in suicide attempts.