Henri-Jean Aubin

Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning.

The extent of structural brain damage and related cognitive deficits has been little described in alcohol-dependent individuals with preserved social functioning. Thus, we investigated the relationship between regional alterations, executive performance, and drinking history. Volumes of gray and white matter were assessed using magnetic resonance imaging voxel-based morphometry in healthy men and in detoxified alcohol-dependent men with good psychosocial functioning. Their executive performance was assessed using neuropsychological tests. Regression analyses were carried out in the regions in which volume differences were detected. Decreases in gray matter were detected bilaterally in alcohol-dependents in the dorsolateral frontal cortex (up to 20% lower), and to a lesser extent in the temporal cortex, insula, thalamus, and cerebellum. Decreases in white matter volume were widespread, being up to 10% in corpus callosum. The degradation of neuropsychological performance correlated with gray matter volume decreases in the frontal lobe, insula, hippocampus, thalami and cerebellum, and with white matter decrease in the brainstem. An early age at first drinking was associated with decreased gray matter volumes in the cerebellum, brainstem (pons), and frontal regions. Regional alteration in gray and white matter volume was associated with impairment of executive function despite preserved social and somatic functioning in detoxified patients. Besides involving frontal regions, these findings are consistent with a cerebello-thalamo-cortical model of impaired executive functions in alcohol-dependent individuals.

Weight gain in smokers after quitting cigarettes: meta-analysis

Objective To describe weight gain and its variation in smokers who achieve prolonged abstinence for up to 12 months and who quit without treatment or use drugs to assist cessation. Design Meta-analysis. Data sources We searched the Central Register of Controlled Trials (CENTRAL) and trials listed in Cochrane reviews of smoking cessation interventions (nicotine replacement therapy, nicotinic partial agonists, antidepressants, and exercise) for randomised trials of first line treatments (nicotine replacement therapy, bupropion, and varenicline) and exercise that reported weight change. We also searched CENTRAL for trials of interventions for weight gain after cessation. Review methods Trials were included if they recorded weight change from baseline to follow-up in abstinent smokers. We used a random effects inverse variance model to calculate the mean and 95% confidence intervals and the mean of the standard deviation for weight change from baseline to one, two, three, six, and 12 months after quitting. We explored subgroup differences using random effects meta-regression. Results 62 studies were included. In untreated quitters, mean weight gain was 1.12 kg (95% confidence interval 0.76 to 1.47), 2.26 kg (1.98 to 2.54), 2.85 kg (2.42 to 3.28), 4.23 kg (3.69 to 4.77), and 4.67 kg (3.96 to 5.38) at one, two, three, six, and 12 months after quitting, respectively. Using the means and weighted standard deviations, we calculated that at 12 months after cessation, 16%, 37%, 34%, and 13% of untreated quitters lost weight, and gained less than 5 kg, gained 5-10 kg, and gained more than 10 kg, respectively. Estimates of weight gain were similar for people using different pharmacotherapies to support cessation. Estimates were also similar between people especially concerned about weight gain and those not concerned. Conclusion Smoking cessation is associated with a mean increase of 4-5 kg in body weight after 12 months of abstinence, and most weight gain occurs within three months of quitting. Variation in weight change is large, with about 16% of quitters losing weight and 13% gaining more than 10 kg.

Pharmacological approaches to methamphetamine dependence: a focused review

Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.

Craving's place in addiction theory: Contributions of the major models

We examine in this paper the unfolding of craving concepts within 18 models that span roughly 60 years (1948-2009). The amassed evidence suggests that craving is an indispensable construct, useful as a research area because it has continued to destabilize patients seeking treatment for substances. The models fall into four categories: the conditioning-based models, the cognitive models, the psychobiological models, and the motivation models. In the conditioning models, craving is assumed to be an automatic, unconscious reaction to a stimulus. In the cognitive models, craving arises from the operation of information processing systems. In the psychobiological models, craving can be explained at least in part by biological factors with an emphasis on motivational components. Finally, in the motivation models, craving is viewed as a component of a larger decision-making framework. It is well accepted that no single model explains craving completely, suggesting that a solid understanding of the phenomenon will only occur with consideration from multiple angles. A reformulated definition of craving is proposed.

Smoking, quitting, and psychiatric disease: a review.

Tobacco smoking among patients with psychiatric disease is more common than in the general population, due to complex neurobiological, psychological, and pharmacotherapeutic mechanisms. Nicotine dependence exposes smokers with co-occurring mental illness to increased risks of smoking-related morbidity, mortality, and to detrimental impacts on their quality of life. The neurobiological and psychosocial links to smoking appear stronger in certain comorbidities, notably depression and schizophrenia. Through its action on the cholinergic system, nicotine may have certain beneficial effects across a range of mental health domains in these patients, including improved concentration and cognition, relief of stress and depressive affect, and feeling pleasurable sensations. Despite the availability of effective smoking cessation pharmacotherapies and psychosocial interventions, as well as increasing evidence that individuals with psychiatric disorders are motivated to quit, nicotine dependence remains an undertreated and under-recognized problem within this patient population. Evidence suggests that provision of flexible and individualized treatment programs may be successful. Furthermore, the complicated relationship observed between nicotine dependence, nicotine withdrawal symptoms, and mental illness necessitates integration of close monitoring in any successful smoking cessation program.

Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studies.

Tobacco use is one of the leading preventable causes of death in developed countries. Since existing medications are only partially effective in treating tobacco smokers, there is a great need for improved medications for smoking cessation. It has been recently proposed that cannabinoid CB1 receptor antagonists represent a new class of therapeutic agents for drug dependence, and notably, nicotine dependence. Here, we will review current evidence supporting the use of this class of drugs for smoking cessation treatment. Pre‐clinical studies indicate that nicotine exposure produces changes in endocannabinoid content in the brain. In experimental animals, N‐piperidinyl‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methylpyrazole‐3‐carboxamide (rimonabant, SR141716) and N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251), two cannabinoid CB1 receptor antagonists, block nicotine self‐administration behavior, an effect that may be related to the blockade of the dopamine‐releasing effects of nicotine in the brain. Rimonabant also seems efficacious in decreasing the influence of nicotine‐associated stimuli over behavior, suggesting that it may act on two distinct neuronal pathways, those implicated in drug‐taking behavior and those involved in relapse phenomena. The utility of rimonabant has been evaluated in several clinical trials. It seems that rimonabant is an efficacious treatment for smoking cessation, although its efficacy does not exceed that of nicotine‐replacement therapy and its use may be limited by emotional side effects (nausea, anxiety and depression, mostly). Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of rimonabant for smoking cessation.

Management of smoking cessation in patients with psychiatric disorders

ABSTRACT Background: There is a close relationship between tobacco smoking and psychiatric disorders, and a higher proportion of individuals with mental health conditions smoke compared with the general population. Due to the increased smoking prevalence in this population, patients with psychiatric conditions are at greater risk of smoking-related morbidity and mortality and experience detrimental effects on their quality of life. However, while the majority of individuals with a history of mental health conditions appreciate that smoking is detrimental to their health, they are less likely to quit smoking and have a lower success rate during quit attempts compared with the general population. Scope: Peer-reviewed articles were identified from PubMed using the inclusive date-range of 1990 – October 2008 and the search terms; depression, mental health, psychiatric disorders, schizophrenia, and smoking cessation. Articles were selected from the search results to provide a general overview of some of the main issues for smokers with psychiatric disorders in general and specifically, those with schizophrenia and depression. The evidence from smoking cessation trials within these populations was also reviewed. Findings: Nicotine has some positive effects on symptoms of psychiatric disorders and it has been proposed that patients with mental health conditions may smoke as a form of self-medication. Further, several studies have shown that some symptoms of psychiatric disorders may be exacerbated by nicotine withdrawal. Therefore, attempts to quit smoking pose additional problems to patients with mental health problems. Conclusion: Traditional programmes for smoking cessation may not always be suitable for psychiatric patients due to their neuropsychological profile. Preliminary evidence suggests that more flexible, open-ended, combination approaches of pharmacotherapy and counselling may be more successful. In addition, identification and treatment of nicotine addiction remains very low in patients with mental health conditions and far more needs to be done to raise the awareness and ability of psychiatrists to diagnose and treat patients with nicotine problems.

A Pilot Evaluation of the Safety and Tolerability of Repeat Dose Administration of Long‐Acting Injectable Naltrexone (Vivitrex®) in Patients With Alcohol Dependence

BACKGROUND : Oral naltrexone is currently used as part of a treatment regimen for alcohol-dependent patients, but its clinical utility is hampered by poor patient adherence. A long-acting injectable naltrexone formulation (Vivitrex) was designed to facilitate patient adherence by providing an extended duration of therapeutic naltrexone over 1 month, thereby eliminating the need for daily dosing. METHODS : A multicenter, randomized, double-blind, placebo-controlled pilot study was conducted to evaluate the safety and tolerability of intramuscular repeat dose administration of this extended-release naltrexone formulation in DSM-IV alcohol-dependent patients. Thirty patients were randomized to treatment with injectable naltrexone (400 mg; n = 25) or a matching placebo injection (n = 5) and were dosed once every 28 days over 4 months. Psychosocial treatment was offered to patients in both treatment groups. Outcome measures related to drinking activity and trough plasma concentrations of naltrexone and its primary metabolite, 6-beta-naltrexol, were evaluated. RESULTS : Injectable naltrexone was generally safe and well tolerated. Reported adverse events were mild to moderate and resolved without intervention; only two patients discontinued due to adverse events. The most common adverse events (nausea and headache) occurred at a similar rate for patients in both treatment groups. Pharmacokinetic analysis confirmed that therapeutic levels of naltrexone were delivered throughout the four 1-month treatment cycles. CONCLUSIONS : The results of this pilot study provide the basis and methods for a larger, more definitive trial to determine the utility of this long-acting injectable naltrexone formulation in the treatment of alcohol-dependent patients.

Diffusion Tensor Tractography in Mesencephalic Bundles: Relation to Mental Flexibility in Detoxified Alcohol-Dependent Subjects

Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n=20) and a group of healthy men (n=24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice.

Strategies for assisting smoking cessation include behavioural counselling to enhance motivation and to support attempts to quit and pharmacological intervention to reduce nicotine reinforcement and withdrawal from nicotine. Three drugs are currently used as first line pharmacotherapy for smoking cessation, nicotine replacement therapy, bupropion and varenicline. Compared with placebo, the drug effect varies from 2.27 (95% CI 2.02, 2.55) for varenicline, 1.69 (95% CI 1.53, 1.85) for bupropion and 1.60 (95% CI 1.53, 1.68) for any form of nicotine replacement therapy. Despite some controversy regarding the safety of bupropion and varenicline, regulatory agencies consider these drugs as having a favourable benefit/risk profile. However, given the high rate of psychiatric comorbidity in dependent smokers, practitioners should closely monitor patients for neuropsychiatric symptoms. Second‐line pharmacotherapies include nortriptyline and clonidine. This review also offers an overview of pipeline developments and issues related to smoking cessation in special populations such as persons with psychiatric comorbidity and pregnant and adolescent smokers.