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.

Impulsivity in cocaine-dependent individuals with and without attention-deficit/hyperactivity disorder.

BACKGROUND: Cocaine-dependent individuals (CDI) display increased impulsivity. However, despite its multifactorial nature most studies in CDI have treated impulsivity monolithically. Moreover, the impact of attention-deficit/hyperactivity disorder (ADHD) has often not been taken into account. This study investigates whether CDI with ADHD (CDI+ADHD) differ from CDI without an ADHD diagnosis and healthy controls (HC) on several impulsivity measures. METHODS: Thirty-four CDI, 25 CDI+ADHD and 28 HC participated in this study. Trait impulsivity was assessed with the motor, attentional and non-planning subscales of the Barratt Impulsiveness Scale (BIS-11). Neurocognitive dimensions of impulsivity were examined with the stop signal task (SST), delay discounting task (DDT) and information sampling task (IST). RESULTS: Relative to HC, both CDI and CDI+ADHD scored higher on all BIS-11 subscales, required more time to inhibit their responses (SST) and sampled less information before making a decision (IST). Greater discounting of delayed rewards (DDT) was only found among CDI+ADHD. Compared to CDI without ADHD, CDI+ADHD scored higher on the BIS-11 non-planning and total scale and showed higher discounting rates. CONCLUSION: CDI score higher on several indices of impulsivity relative to HC, regardless of whether they have concomitant ADHD or not. CDI+ADHD are specifically characterized by a lack of future orientation compared to CDI without ADHD. © 2015 S. Karger AG, Basel.

Effect of modafinil on cognitive functions in alcohol dependent patients: a randomized, placebo-controlled trial.

Cognitive deficits are highly prevalent in alcohol-dependent (AD) patients and may have a detrimental impact on treatment response and treatment outcome. Enhancing cognitive functions may improve treatment success. Modafinil is a promising compound in this respect. Therefore, a randomized double-blind placebo-controlled trial was conducted with modafinil (300 mg/d) or placebo in 83 AD patients for 10 weeks. Various cognitive functions (digit span task, Tower of London task, Stroop task) were measured at baseline, during and after treatment. Compared to placebo, modafinil improved verbal short-term memory (number of forward digit spans) (p=0.030), but modafinil exerted a negative effect on the working memory score of the digit span task (p=0.003). However, subgroup analyses revealed that modafinil did improve both working memory and verbal short-term memory in AD patients with a poor working memory ability at baseline (25% worst performers), whereas no significant treatment effect of modafinil was found on these two dependent variables in patients with good working memory skills at baseline (25% best performers). No effect of modafinil was found on measures of planning (Tower of London task) and selective attention (Stroop task). Further research is needed to better understand the relationship between cognitive remediation and treatment outcome in order to design targeted treatments.

Modafinil modulates resting-state functional network connectivity and cognitive control in alcohol-dependent patients.

BACKGROUND: Chronic alcohol abuse is associated with deficits in cognitive control functions. Cognitive control is likely to be mediated through the interaction between intrinsic large-scale brain networks involved in externally oriented executive functioning and internally focused thought processing. Improving the interaction between these functional brain networks could be an important target for treatment. Therefore, the current study aimed to investigate the effects of the cognitive enhancer modafinil on within-network and between-network resting-state functional connectivity and cognitive control functions in alcohol-dependent patients. METHODS: In a double-blind, placebo-controlled cross-over design, resting-state functional magnetic resonance imaging and a Stroop task were employed in alcohol-dependent patients (n = 15) and healthy control subjects (n = 16). Within-network and between-network functional connectivity was calculated using a combination of independent component analysis and functional network connectivity analysis. RESULTS: Modafinil significantly increased the negative coupling between executive networks and the default mode network, which was associated with modafinil-induced improvement in cognitive control in alcohol-dependent patients. CONCLUSIONS: These findings demonstrate that modafinil at least partly exerts its effects by targeting intrinsic functional relationships between large-scale brain systems underlying cognitive control. The current study therefore provides a neurobiological rationale for implementing modafinil as an adjunct in the treatment of alcohol dependence, although clinical studies are needed to substantiate this promise.

Effect of modafinil on impulsivity and relapse in alcohol dependent patients: a randomized, placebo-controlled trial.

Poor impulse control plays an important role in the development, course and relapse of substance use disorders. Therefore, improving impulse control may represent a promising approach in the treatment of alcohol dependence. This study aimed to test the effect of modafinil on impulse control and alcohol use in alcohol dependent patients (ADP) in a randomized, double-blind, placebo-controlled trial. Eighty-three abstinent ADP were randomized to 10 weeks modafinil (300 mg/d) or placebo. Alcohol use was quantified using the timeline follow-back method and was assessed until 6 months after treatment discontinuation. Impulsivity was assessed using self-report questionnaires (Barratt Impulsiveness Scale; State Impulsivity questionnaire) and neurocognitive tasks (Stop Signal Task; Delay Discounting Task) administered before, during and after treatment. Modafinil significantly improved self-report measures of state impulsivity, but had no effect on percentage of abstinent days or percentage of heavy drinking days, nor on the behavioral measures of impulsivity. However, subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022) and tended to increase the percentage of abstinent days (p=.066) in ADP with poor response inhibition at baseline, whereas modafinil increased the percentage of heavy drinking days (p=.003) and reduced the percentage of abstinent days (p=.002) in patients with better baseline response inhibition. Overall results do not favor the use of modafinil in order to reduce relapse or relapse severity in ADP, and caution is required in prescribing modafinil to a non-selected sample of ADP. Further research on the effect of modafinil in ADP with poor baseline response inhibition is warranted.

Effects of modafinil on neural correlates of response inhibition in alcohol-dependent patients.

BACKGROUND: Impaired response inhibition is a key feature of patients with alcohol dependence. Improving impulse control is a promising target for the treatment of alcohol dependence. The pharmacologic agent modafinil enhances cognitive control functions in both healthy subjects and in patients with various psychiatric disorders. However, very little is known about the underlying neural correlates of improvements in response inhibition following modafinil. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover study using functional magnetic resonance imaging with a stop signal task to examine effects of a single dose of modafinil (200 mg) on response inhibition and underlying neural correlates in abstinent alcohol-dependent patients (AD) (n = 16) and healthy control subjects (n = 16). RESULTS: Within the AD group modafinil administration improved response inhibition (reflected by the stop signal reaction time [SSRT]) in subjects with initial poor response inhibition, whereas response inhibition was diminished in better performing subjects. In AD patients with initial poor response inhibition, modafinil-induced SSRT improvement was accompanied by greater activation in the thalamus and supplementary motor area (SMA) and reduced connectivity between the thalamus and the primary motor cortex. In addition, the relationship between baseline response inhibition and modafinil-induced SSRT improvement was mediated by these changes in thalamus and SMA activation. CONCLUSIONS: These findings indicate that modafinil can improve response inhibition in alcohol-dependent patients through its effect on thalamus and SMA function but only in subjects with poor baseline response inhibition. Therefore, baseline levels of response inhibition should be taken into account when considering treatment with modafinil in AD.

Age of onset and neuropsychological functioning in alcohol dependent inpatients.

BACKGROUND: Differences in clinical characteristics between early and late onset alcohol dependent patients have been examined intensively, but little is known about the differences in neuropsychological functioning between these patient groups. Clinical characteristics and neuropsychological functions of inpatients with early onset and late onset alcohol dependence are therefore investigated in this study. METHODS: Ninety-three abstinent alcohol dependent inpatients meeting a current diagnosis of DSM-IV alcohol dependence were divided into early onset alcohol dependent patients (EOA; ≤25 years; n = 36) and late onset alcohol dependent patients (LOA; >25 years; n = 57). Patients using psychoactive medication and patients dependent on other substances than alcohol (and nicotine) were excluded. A comprehensive neuropsychological test battery was administered. RESULTS: EOA reported higher trait impulsivity, antisocial traits, and attention deficit hyperactivity disorder-related traits and exhibited an impulsive reflection style, especially in a high-risk context, compared with LOA. Against expectations, EOA performed significantly better on measures of planning, cognitive control, visual memory, and delayed recognition memory than LOA, whereas no significant group differences occurred on measures of delay discounting, digit span, and attention. Better Stroop interference, better visual memory, and a more impulsive reflection style was predictive of an early age of onset, and explained a significant and additional amount of variance (18.8%) on top of the clinical characteristics, together explaining 53.4% of the variance. CONCLUSIONS: Both clinical characteristics and neuropsychological variables contributed independently to the age of onset of problematic alcohol use. Results indicate that especially an impulsive reflection style, besides higher trait impulsivity, may be the core feature of early onset alcohol dependence. However, the contribution of the neuropsychological variables is complex and more research is needed to clarify the role of psychiatric comorbidity and poly-substance abuse in an unselected sample of alcohol dependent patients.

Alcohol use and hazardous drinking among medical specialists.

BACKGROUND: Alcohol use among medical specialists remains a delicate topic. However, the number of prevalence studies remains very limited in Western European countries. AIMS: To explore alcohol use and hazardous drinking among male and female medical specialists. METHODS: All medical specialists in Belgium--a typical Western European country regarding alcohol use--were invited to participate. Alcohol use and abuse were measured using the Alcohol Use Disorder Identification Test (AUDIT) and the CAGE screen (acronym based on the four items it contains: 'Cut down drinking', 'Annoyed by criticism', 'Guilty feelings' and 'Eye opener'). RESULTS: A sample of 1,501 specialists completed the survey. The composition of the sample was comparable with that of the overall population of specialists in Belgium regarding gender, age and specialties. A proportion of 18% of the specialists could be classified as hazardous drinkers and 16.8% reported binge drinking at least once a month. Female medical specialists drank less than their male counterparts; however, a substantial proportion of female specialists (14.9%) displayed higher risk levels of hazardous drinking. Significant differences were found between specialties on the CAGE screen. Finally, younger medical specialists tended to display healthier alcohol use patterns compared with their older counterparts. CONCLUSION: Medical specialists tend to indulge in more hazardous drinking compared with the general population (10%). The alcohol use patterns of female doctors tend to move towards those of males.

Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression.

INTRODUCTION: Bipolar disorder is a psychiatric illness with recurring episodes of mania and depression. Armodafinil , the R-enantiomer of modafinil, approved for treating excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder, is possibly effective as an adjunctive treatment for bipolar depression. AREAS COVERED: This review covers the pharmacokinetics of armodafinil, with an emphasis on its use in bipolar depression. Its clinical efficacy in the treatment of bipolar depression is evaluated, along with current data regarding its safety and tolerability. EXPERT OPINION: One placebo-controlled trial is available, in which armodafinil was efficacious as an adjunctive treatment in bipolar depression. Armodafinil shows a linear pharmacokinetic profile over a broad dose range of 50 - 400 mg (maximal plasma concentration and area under concentration-time curve). Compared with modafinil, an equivalent dose of armodafinil attains higher blood concentrations 4 - 6 h post-dose. The possibility of drug interactions is generally low, although interactions have been shown with some drugs used in bipolar disorder, through mild CYP3A4-induction and CYP2C19-inhibition. Armodafinil is well tolerated and presents a possible new treatment option for bipolar depression. However, further investigation is still needed in order to confirm its efficacy and to clarify its role in the treatment of bipolar depression.