Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Using Biotinylated myo-Inositol Hexakisphosphate to Investigate Inositol Pyrophosphate-Protein Interactions with Surface-Based Biosensors.

Inositol pyrophosphates (PP-InsPs) are highly phosphorylated molecules that have emerged as central nutrient messengers in eukaryotic organisms. They can bind to structurally diverse target proteins to regulate biological functions, such as protein-protein interactions. PP-InsPs are strongly negatively charged and interact with highly basic surface patches in proteins, making their quantitative biochemical analysis challenging. Here, we present the synthesis of biotinylated myo-inositol hexakisphosphates and their application in surface plasmon resonance and grating-coupled interferometry assays, to enable the rapid identification, validation, and kinetic characterization of InsP- and PP-InsP-protein interactions.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

BACKGROUND: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. METHODS: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. RESULTS: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). CONCLUSIONS: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level.

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.

Changes in Pro-Inflammatory Markers in Detoxifying Chronic Alcohol Abusers, Divided by Lesch Typology, Reflect Cognitive Dysfunction.

AIM: To investigate pro-inflammatory markers in the blood and associate with cognitive impairment. METHODS: Il-6 and ferritin were assayed in the blood of 27 patients, divided according to Lesch typology, at the commencement and after 21 days of detoxification, together with a battery of cognitive tests. RESULTS: A significantly higher mean level of IL-6 was present in the blood of patients with Lesch typology 1 compared to the other typologies 2 and 3 on admission to the Detoxification Ward which did not alter significantly after detoxification. The mean level of IL-6 was initially elevated in Lesch typology 2 alcohol abusers and declined to the reference range after detoxification. Lesch typology 3 alcohol abusers showed normal levels of IL-6 at both time points. Only in Lesch typology 1 were the levels of ferritin and IL-10 significantly elevated at the start of the detoxification process. Cognitive impairment, as ascertained by Stroop test and Brown-Peterson procedure was greater in Lesch typology 1 than the other 2 patient groups. CONCLUSION: Such data might indicate a greater degree of neuroinflammation in Lesch typology 1 alcoholic patients. SHORT SUMMARY: Dividing a heterogeneous group of alcoholic subjects into homogenous groups according to Lesch typology, identifies a greater pro-inflammatory profile in Lesch typology 1 patients who also showed greater cognitive impairment.

Genetic markers of comorbid depression and alcoholism in women.

BACKGROUND: Alcohol dependence (AD) is often accompanied by comorbid depression. Recent clinical evidence supports the benefit of subtype-specific pharmacotherapy in treating the population of alcohol-dependent subjects with comorbid major depressive disorder (MDD). However, in many alcohol-dependent subjects, depression is a reactive response to chronic alcohol use and withdrawal and abates with a period of abstinence. Genetic markers may distinguish alcohol-dependent subjects with MDD not tied chronologically and etiologically to their alcohol consumption. In this work, we investigated the association of adenylyl cyclase genes (ADCY1-9), which are implicated in both AD and mood disorders, with alcoholism and comorbid depression. METHODS: Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females. RESULTS: We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics. CONCLUSIONS: Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of the alcoholism/depression phenotype, and the use of these genetic markers may aid in choosing appropriate and beneficial treatment strategies.

Serbian and Austrian alcohol-dependent patients: a comparison of two samples regarding therapeutically relevant clinical features.

AIMS: To support the Serbian Expert Board in setting up reimbursement for modern pharmacotherapeutic support, we compared a Serbian sample of alcohol-dependent patients with an Austrian sample, in order to detect differences that might inhibit the introduction of anti-craving medications in Serbia. METHODS: One hundred and twenty-seven (116 males) alcohol-dependent patients in Serbia and 136 in Austria (78 males) were enrolled consecutively from January 2011 to March 2012 and were assessed using the Lesch alcoholism typology instrument (LAT). RESULTS: Age of onset was slightly higher in the Austrian sample (28.5 vs. 30.0; P = 0.10). The Serbian sample showed a higher rate of anxiety disorders than the Austrian sample (89.8 vs. 26.5%, P ≤ 0.0001). Suicidal tendencies, independent of alcohol intake or withdrawal syndrome, were higher in the Austrian sample (1.6 vs. 13.2% P ≤ 0.0001). There was no difference between the two samples in Lesch-Type IV (26 vs 28); there was a slight excess in the Serbian sample of Type I (15 vs. 10). In Austria, significantly more Type II patients (32 vs. 52) had been included, while the Serbian sample comprised significantly more Type III patients. CONCLUSIONS: Austrian and Serbian patients are quite similar, without any showing any factor that would detract from the potential value of modern anti-craving medications in Serbia. The differences in anxiety disorders might be due to the 1990s war and should be investigated further.

Relationship between substance use and body mass index in young males.

Recent findings in basic scientific research, such as neurobiological and neuroimaging studies, have suggested common pathways for food and drug intake. It was hypothesized that both compete for the same brain reward sites, and that a higher body mass index (BMI) may be associated with lower substance use. The aim of this study was to investigate the relationship between BMI and substance use in a large sample of young male adults. The sample consisted of 1,902 18-year-old males from a province of Austria in a naturalistic cross-sectional setting. Questionnaires were administered to assess alcohol abuse and dependence (CAGE) and nicotine dependence (Heavy Smoking Index). Urine samples were collected to assess the prevalence of recent illicit drug use. Associations between BMI and substance use were calculated by means of logistic regression analyses. An inverse relationship between BMI and recent illicit drug use was found. This relationship remained significant after adjusting for possible confounding factors such as level of education, nicotine dependence, breath carbon monoxide (CO) levels, and alcohol abuse and dependence. No significant association was found between BMI and nicotine and alcohol dependence. A higher BMI was associated with lower illicit drug use in our sample of young adult males. These results provide further evidence for the hypothesis that food and drugs may compete for the same brain reward sites.

Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. AIMS: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. METHODS: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. RESULTS: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites (n = 3-66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. CONCLUSIONS: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648423.

Amino-terminal pro-B-type brain natriuretic peptide: screening for cardiovascular disease in the setting of alcoholism.

AIMS: N-terminal pro-BNP (NtBNP) has attracted attention as a biomarker for heart failure. The aims of our study are (a) to characterize the role of NtBNP as a biological marker in the setting of alcoholism; (b) to describe potential gender differences with respect to NtBNP; (c) to correlate NtBNP with other clinical and haemodynamic variables. METHODS: We examined 83 alcohol-dependent patients according to International Classification of Disease 10th Revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV; 59 males and 24 females, age: 50 ± 10.5 years) referred to the department of psychiatry for alcohol withdrawal therapy. In these patients, we determined NtBNP, markers of alcohol abuse and transthoracic echocardiography to determine systolic left ventricular ejection fraction (EF). These measurements were repeated after alcohol withdrawal. RESULTS: At Day 1 of alcohol withdrawal, 43 patients (52%; 27 males and 16 females) had elevated NtBNP levels (394.4 ± 438.7 pg/ml) despite normal EF (64.7 ± 6.2%). After withdrawal therapy (16.6 ± 7.8 days), NtBNP decreased significantly (228.6 ± 251.2 pg/ml; P < 0.01), despite unchanged EF (65.0 ± 5.8%; P = ns). This was the case in both males and females (328.9 ± 235.5 to 216.7 ± 194.3 pg/ml; P < 0.05 vs. 492.7 ± 635.7 to 246.6 ± 327.7 pg/ml; P < 0.05). Elevated NtBNP levels were related significantly to the history of arterial hypertension (P < 0.05). CONCLUSION: This study highlights the fact that NtBNP can be elevated in the setting of alcoholism. The elevation in NtBNP is unrelated to EF and is reversible after alcohol withdrawal. We suggest a subclinical detrimental effect of alcohol abuse on cardiac function.

Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study.

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

Comparison of alcohol-dependent patients at a gastroenterological and a psychiatric ward according to the Lesch alcoholism typology: implications for treatment.

AIMS: To assess the clinical and biological status of alcohol-dependent patients admitted to a psychiatric or a gastroenterological ward, assessing and comparing dimensions important for prescribing treatment for withdrawal and relapse prevention. METHODS: Eighty patients, alcohol-dependent according to international classification of diseases tenth revision and diagnostic and statistical manual, text revised, version IV, admitted to the Vienna General Hospital between January 2005 and  November 2006, were examined, of whom 44 were admitted to the psychiatric ward and 36 to the gastroenterological ward. Dimensions of alcohol dependence were assessed using a computerized structured interview, the Lesch alcoholism typology (LAT). Biological markers and the model for end-stage liver disease (MELD) score defined the severity of alcohol-related physical disturbances. RESULTS: As might be expected, gastroenterological patients had more advanced physical diseases than psychiatric patients, and affective disorders and suicidal tendencies were significantly commoner among the psychiatric patients. Thus, LAT Type II patients were overrepresented at the gastroenterological ward and LAT Type III patients at the psychiatric ward. CONCLUSION: The severity of somatic diseases and psychiatric disorders as well as the distribution of the four types according to Lesch differ between alcohol-dependent patients admitted to a psychiatric ward or a gastroenterological ward. Regarding the positive long-term outcome, different evidence-based medical treatment approaches for withdrawal and relapse prevention are needed for these patients.

Post-marketing and clinical safety experience with sodium oxybate for the treatment of alcohol withdrawal syndrome and maintenance of abstinence in alcohol-dependent subjects.

Introduction: Sodium oxybate (SMO) has been approved in Italy and in Austria for the treatment of alcohol use disorder (AUD). This study describes the cumulative postmarketing and clinical safety experience with SMO in AUD.Areas covered: Safety data for SMO at approved posology in AUD were identified from: (i) the clinical trial registries of the US National Institutes of Health (NIH) and the European Medicines Agency (EMA), (ii) reports from the biomedical literature and (iii) available pharmacovigilance safety information from the EMA.Expert opinion: Safety data from 3 recent large randomized clinical studies (520 participants) and 43 earlier clinical studies (2547 participants) showed that SMO has a good safety profile in AUD patients. The safety profile was confirmed by pharmacovigilance data resulting from 299 013 patients exposed to SMO in Austria and Italy. Main adverse events were transitory dizziness and vertigo. Serious adverse events were rare. No death attributable to SMO has been reported. Risks of abuse or dependence are low in patients without psychiatric comorbidities or poly-drug use. The adverse events of SMO are transitory and do not require discontinuation of treatment. SMO abuse or dependence are extremely rare in patients without psychiatric comorbidities or poly-drug use.

Breath alcohol level and plasma amino acids: a comparison between older and younger chronic alcohol-dependent patients.

AIM: The aim of the present study is to examine the distribution of plasma excitatory and inhibitory amino acids, according to the age and current breath alcohol levels (BrAl+/-), of alcohol-dependent patients. PARTICIPANTS AND METHODS: 78 alcohol-dependent patients (mean age=46.2+/-11 years, men/women=54/24) were clinically tested, including the determination of the major excitatory as well as inhibitory amino acids. The independent variables were gender, age and current alcohol consumption measured with the breath alcohol level (BrAl+/-status). RESULTS: In comparison to BrAl negatives, BrAl positives had higher plasma levels of glutamic acid (P=0.01) and proline (P=0.026), and lower levels of aminobutyric acid (P=0.002), serine (P=0.031) and urea (P=0.01). In the BrAl positives, no age effect was found related to the plasma amino acids. In contrast, the BrAl negatives displayed age-related differences. The older (>or=50 years) BrAl negative patients had higher plasma levels of cystine, tyrosine, citrulline and urea, and lower histidine levels, compared to the younger group (<50 years). In general, differences in plasma levels of certain amino acids were dependent on gender, BrAl status, age and biochemical markers (GGT, MCV) of alcohol abuse. CONCLUSIONS: Abstaining patients (BrAl-/) display age-related differences in AAs' distribution, while active drinking (BrAl+/) seems to even out those differences, underpinning the hypothesis that drinking mimics changes seen with advanced age.

No evidence of subgroups found in amphetamine consumers in Iran.

Amphetamine type substances are the second most commonly consumed illicit drug type and their use is an important contributor to the global burden of disease. This investigation set out to determine whether, similar to alcohol or nicotine addiction, subgroups of consumers can also be found in amphetamine addicts. 204 consumers of methamphetamine only (n = 50) or both methamphetamine and heroin (n = 154) have been investigated in Mashhad, Iran by means of "Lesch Alcoholism Typology". No significant differences in consumption pattern or age of onset have been found between the different types. Many subjects, however, reported symptoms of anxiety (n=78) or depression (n = 129) prior to drug use. These findings highlight the need for high quality epidemiological studies further addressing this issue.

Multiple substance use among young males.

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Attention deficit hyperactivity disorder and substance abuse: An investigation in young Austrian males.

BACKGROUND: Many studies have found an association between Substance Use Disorders (SUDs) and Attention Deficit Hyperactivity Disorder (ADHD) in children, adolescents and adults. We intended to determine whether substance abuse and SUDs are associated with former and current ADHD symptomatology in a non-clinical sample of 17 and 18 year old males. METHOD: A representative sample of 3280 young men (6.8% of all males born in Austria in the respective year) was investigated during the examination for military service. We collected data on past (WURS) and current (ADHD symptom checklist) ADHD symptomatology, substance abuse, parental substance use and abuse and motives for substance use. RESULTS: Measured by WURS, 10.1% had scored positive for past ADHD symptoms. 2.7% of all subjects stated that they have been treated for ADHD and 1.5% reported that they had at one point received pharmacological treatment for the condition. Abuse of alcohol, nicotine and illicit substances was significantly (p<.01) more frequent in subjects with ADHD syndrome. Perceived parental alcohol abuse increased the risk for ADHD in the offspring. Motives for substance use differed greatly between groups. LIMITATIONS: The sample consists of men only. Subjects had to be fit enough to be enlisted military service, generating a possible bias towards healthier subjects. The cross-sectional design does not allow conclusions about the temporal relationships between ADHD symptoms and substance abuse. CONCLUSION: Identification of vulnerability factors for comorbid ADHD and SUD in adolescence should be intensified. Preventive strategies ought to be established.

Motivational factors and negative affectivity as predictors of alcohol craving.

Craving is thought to play an important role in alcohol use disorders. The recent inclusion of "craving" as a formal diagnostic symptom calls for further investigation of this subjective phenomenon with multiple dimensions. Considering that alcohol-dependent patients compensate negative physical/emotional states with alcohol, the aim of this study is to investigate alcohol craving and its correlation with drinking measures and affective personality dimensions. A sample of 135 alcohol-dependent patients (104 males and 31 females) was collected from a clinical setting. Subjects self-rated their cravings (Penn Alcohol Craving Scale) and the stage of change. Several personality scales were also administered. Craving was related to drinking status, abstinence time, age, and taking steps. After controlling for these conditions, psychological characteristics related to low self-concept, neuroticism, cyclothymic affective temperament, depression, and hostility were found to be predictors of craving in sober alcohol-dependent patients. Our results support craving as a component of the phenomenology of alcohol dependence and highlight the presence of unpleasant feelings as predictors of craving in sober alcohol-dependent patients without co-occurring psychiatric conditions. The predisposition to experience negative emotions may induce a stronger craving response and increase the likelihood of a first drink and a subsequent loss of control.

The influence of reported ADHD and substance abuse on suicidal ideation in a non-clinical sample of young men.

This study intended to determine whether former and current ADHD symptomatology is associated with suicidal ideation in a non-clinical sample of 18 year old males. We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a screening for substance abuse, past (WURS) and current (ADHD symptom checklist) ADHD symptomatology and an interview about suicidal ideations. We found a correlation of suicidal ideations with a history of ADHD symptomatology. ADHD symptoms were strongly consistent over time. These results indicate that a history of (diagnosed or undiagnosed) ADHD could be a predictor for suicidal ideations. Surveying a history of ADHD in primary care might help identify subjects at risk for suicidal tendencies.

Craving and other characteristics of the comorbidity of alcohol and nicotine dependence.

PURPOSE: In this cross-sectional study we compared alcohol-dependent smokers and non-alcohol-dependent smokers with respect to intensity of nicotine dependence, craving conditions, sleep disturbances, comorbidity with major depression, reasons for smoking, accompanying somatic diseases and patients' prolonged abstinence from smoking during the 3 years preceding the study. SUBJECTS AND METHODS: Fifty-one alcohol-dependent smokers and 327 non-alcohol-dependent smokers diagnosed as ICD-10 and DSM-IV-nicotine dependent, were investigated by means of the Fagerström Test for Nicotine Dependence, the Lübeck Craving-Recurrence Risk Questionnaire and the Lesch Alcohol Dependence Typology (both adapted to smoking). RESULTS: The intensity of nicotine dependence was more enhanced in alcohol-dependent smokers compared to non-alcohol-dependent smokers. Several variables of all factors of craving ("depressive mood", "stimulation", "relaxation", "socially triggered tension") were significantly increased in alcohol-dependent patients (P<0.05). Alcohol-dependent smokers showed depressive symptoms and sleep disturbances, whilst non-alcohol-dependent individuals mainly smoked for stress release and weight control. DISCUSSION: Our study demonstrates that the intensity of nicotine dependence, several conditions of craving for nicotine, sleep disturbances and symptoms of depression appear to be enhanced in alcohol-dependent smokers compared with non-alcohol-dependent smokers. Conclusions. - It is hoped that the factors of craving and reasons for smoking identified in this study will contribute to a better understanding of smoking temptation in alcohol-dependent smokers and non-alcohol-dependent smokers in future.