Colin O'Gara

Association between dopamine transporter genotypes and smoking cessation: a meta-analysis

This review assessed the evidence of an association between genotypes of the dopamine transporter (DAT1, SLC6A3) 3′ untranslated region (3′UTR) variable number of tandem repeats (VNTR) and smoking cessation. Five studies (seven cohorts) comprising 2155 subjects were included in the meta‐analysis. All gave data on the number of smokers who had stopped smoking and the number still smoking for those with one or more variant 9‐repeat alleles and other genotypes. Three studies (comprising five cohorts) were cross‐sectional population surveys and two were smoking cessation treatment programs with follow‐up. Four of the five studies (six of the seven cohorts) showed a trend in favor of cessation when the variant 9‐repeat allele was present, although only one study showed a statistically significant effect. The pooled odds ratio in favor of a greater likelihood of cessation for the variant 9‐repeat allele was 1.15 [95% confidence interval (CI) = 0.97–1.37]. In a more refined analysis where cohorts within studies were treated as separate samples and adjusted odds ratios were used, the overall pooled odds ratio in favor of cessation with the 9‐repeat alleles was 1.20 (95% CI = 1.01–1.43). These results support the hypothesis that the DAT1 3′UTR VNTR polymorphism is associated with smoking cessation. One or more variant 9‐repeat alleles relative to the more common 10‐repeat allele confers a greater likelihood of cessation, indicative of lower dependence on tobacco. The effect was a 20% increase in the odds of cessation for those with a variant allele.

Is methadone too dangerous for opiate addiction

The case for using a safer alternative, buprenorphine, is strong M ethadone is an effective treatment for heroin addiction, and it remains the mainstay of drug treatment for opiate dependence in the United Kingdom.1 The lethal dose of methadone is estimated at 50 mg for an opiate-naive adult.2 Nevertheless, many authorities recommend that methadone doses should be gradually increased to maintenance doses of 80-120 mg1—that is, twice the lethal dose for non-users. The greatly increased risk to users from methadone, particularly black market methadone, thus remains a major concern. Buprenorphine is a partial agonist that has a lower potential for causing respiratory depression than many other opioids, including methadone and heroin.3 It is increasingly used in the United Kingdom to treat opiate dependence, with guidelines for clinical management in primary and secondary care summarised by Ford et al4 and Taikato et al.5 It is time it replaced methadone as the mainstay of drug treatment for opiate dependence. A long running debate continues …

Substance misuse training among psychiatric doctors, psychiatric nurses, medical students and nursing students in a South London psychiatric teaching hospital

Background: Health professionals play an important role in the detection and subsequent management of individuals who misuse substances. Aim: This article aimed to assess self-reported levels of training received by psychiatric doctors, nurses, medical students and nursing students in a South London psychiatric teaching hospital. Method: Self-completion questionnaire assessing key aspects of training. Findings: We found low overall levels of reported training in substance misuse. Of the reported training received, most was theoretical rather than clinical. The highest level of reported training was in alcohol misuse compared to illicit drug and tobacco misuse. High numbers of respondents reported feeling responsible for helping individuals with substance misuse difficulties but low numbers actually felt skilled to do so, indicating high levels of awareness without the requisite training. Conclusion: Our findings suggest that more resources should be focused on teaching psychiatric doctors, nurses, medical students and nursing students the key issues in substance misuse, and that this training should be clinically grounded, to alleviate the perceived low levels of reported clinical training in this study and the resulting lack of confidence.

Randomized trial of nicotine replacement therapy (NRT), bupropion and NRT plus bupropion for smoking cessation: effectiveness in clinical practice

Background and aims Bupropion was introduced for smoking cessation following a pivotal trial showing that it gave improved efficacy over the nicotine patch and also suggesting combination treatment was beneficial. We tested in clinical practice for an effectiveness difference between bupropion and nicotine replacement therapy (NRT), whether the combination improves effectiveness and whether either treatment might be more beneficial for certain subgroups of smokers. Design Open-label randomized controlled trial with 6-month follow-up. Setting Four UK National Health Service (NHS) smoking cessation clinics. Participants Smokers (n = 1071) received seven weekly behavioural support sessions and were randomized to an NRT product of their choice (n = 418), bupropion (n = 409) or NRT plus bupropion (n = 244). Measures The primary outcome was self-reported cessation over 6 months, with biochemical verification at 1 and 6 months. Also measured were baseline demographics, health history, smoking characteristics and unwanted events during treatment. Findings Abstinence rates for bupropion (27.9%) and NRT (24.2%) were not significantly different (odds ratio = 1.21, 95% confidence interval = 0.883–1.67), and the combination rate (24.2%) was similar to that for either treatment alone. There was some evidence that the relative effectiveness of bupropion and NRT differed according to depression (χ2 = 2.86, P = 0.091), with bupropion appearing more beneficial than NRT in those with a history of depression (29.8 versus 18.5%). Several unwanted symptoms were more common with bupropion. Conclusion There is no difference in smoking cessation effectiveness among bupropion, nicotine replacement therapy and their combination when used with behavioural support in clinical practice. There is some evidence that bupropion is more beneficial than nicotine replacement therapy for smokers with a history of depression.

Association between DRD2/ANKK1 Taq1A genotypes, depression and smoking cessation with nicotine replacement therapy

Objectives Tobacco dependence and depression are believed to have a common familial component, most probably genetic, and mood disorders have been reliably associated with failure to stop smoking. Variant genotypes of the Taq1A (DRD2/ANKK1, 32806T, rs1800497) polymorphism have been associated with failure to stop smoking in some studies, but not others. We investigated the association between Taq1A genotypes and smoking cessation, while also considering mental health. Materials and methods This was a prospective study in 419 smokers who attended a smoking cessation clinic and used standard doses of nicotine replacement therapy. DNA samples and baseline measures including demographics, severity of tobacco dependence, mental health history and history of drug misuse were taken. Smoking cessation at the end of treatment was biochemically verified using expired-air carbon monoxide. Results We found no simple relation between Taq1A genotype and smoking cessation, although the association between cessation and lifetime depression was significantly modified by genotype. The relationship was such that for those having only common alleles there was no association between depression and stopping smoking, whereas for those with at least one variant allele (A1A2/A1A1) depression was associated with a two-fold reduction in the likelihood of stopping. Conclusion Those having a Taq1A variant allele and a history of depression are likely to experience particular difficulty when trying to stop smoking and may require treatment other than standard doses of nicotine replacement. This finding might explain previous conflicting results for Taq1A and smoking cessation in studies where depression history was not measured, and may help to explain the underlying link between depression and smoking.

A GSTP1 functional variant associated with cocaine dependence in a Brazilian population.

Cocaine dependence aetiology is complex and genetically influenced. We hypothesize that, for many users, efficient metabolism of cocaine and its toxic byproducts aids persistent cocaine use, such as that leading to dependence. The glutathione-S-transferases - in particular, GST-Pi - may be important in preventing cocaine and alcohol-induced oxidative damage. We genotyped a GST-Pi functional polymorphism (Ile105Val) in 654 male cocaine users and 572 controls from Brazil. Genotype and allele frequencies of Ile105Val differed significantly (chi = 6.74; P=0.03 and chi = 6.54; P = 0.01, respectively). Ile/Ile cocaine dependents had an OR = 1.31 (95%CI: 1.04-1.65), and Ile/Ile dependents consuming >50 units alcohol weekly an OR of 1.44 (95% CI:1.06-1.96). Population stratification was assessed and did not affect the results. These data require replication but do suggest that the high activity Ile105 GST-Pi allele may influence the aetiology and development of cocaine dependence.

Association of the serotonin transporter gene, neuroticism and smoking behaviours.

AbstractCigarette consumption and smoking cessation are influenced in part by genes. Personality traits have also been implicated in the aetiology of smoking. Neuroticism, a personality trait with a heritable component, correlates well with anxiety and depression, increasing the risk of being a smoker and decreasing the chance of smoking cessation. Several prior studies in non-British populations have given conflicting results as to whether some genetic polymorphisms affect the relationship between smoking and neuroticism. This study investigated the influence of serotonin transporter (5HTTLPR) genotypes on a composite measure of neuroticism and cigarette consumption/smoking cessation in a British population. Although neuroticism was significantly associated with cigarette consumption and smoking cessation, genotype did not affect this relationship. Our results do not support initial interest in utilising 5HTTLPR genotypes in combination with neuroticism ratings for predicting outcome in smoking cessation clinical settings.

Validation of the 13-Item Beck Depression Inventory in alcohol-dependent people

Aims. To validate a self-administered questionnaire (the 13-item Beck Depression Inventory) as an instrument for assessing depressive symptoms in alcohol-dependent people. Design, setting and participants. One hundred and eight treatment-seeking alcohol-dependent patients were recruited from a teaching hospital substance misuse facility. Measures. The Beck Depression Inventory, Montgomery Asberg Depression Rating Scale and Hamilton Rating Scale for Depression were administered. Scores from each instrument were compared using correlation coefficients. Findings. Correlation between the Beck Depression Inventory and Montgomery Asberg Depression Rating Scale was 0.763. The Beck Depression Inventory achieved a high degree of consistency/reliability (Cronbachs α=0.8847). Receiver operated curve analysis gave an optimal cut-off on the 13-item Beck Depression Inventory of 18/19 out of 39 as a screening tool to identify cases with moderate or severe depression. This cut-off gave a sensitivity of 79% and a specificity of 79% compared to the Montgomery Asberg Depression Rating Scale. The diagnostic efficient was 82% for moderate to severe depression compared to the Montgomery Asberg Depression Rating and 85% compared to Hamilton Depression Rating Scale. Conclusions. The self-administered Beck Depression Inventory is a feasible, valid and reliable alternative to the interview for detecting change in depressive symptoms in alcohol-dependent people. This would be particularly useful in services with very limited staffing time such as primary care.

Randomized trial of NRT, bupropion, and NRT plus bupropion for smoking cessation: effectiveness in clinical practice

Background and aims Bupropion was introduced for smoking cessation following a pivotal trial showing that it gave improved efficacy over the nicotine patch and also suggesting combination treatment was beneficial. We tested in clinical practice for an effectiveness difference between bupropion and nicotine replacement therapy (NRT), whether the combination improves effectiveness and whether either treatment might be more beneficial for certain subgroups of smokers. Design Open-label randomized controlled trial with 6-month follow-up. Setting Four UK National Health Service (NHS) smoking cessation clinics. Participants Smokers (n = 1071) received seven weekly behavioural support sessions and were randomized to an NRT product of their choice (n = 418), bupropion (n = 409) or NRT plus bupropion (n = 244). Measures The primary outcome was self-reported cessation over 6 months, with biochemical verification at 1 and 6 months. Also measured were baseline demographics, health history, smoking characteristics and unwanted events during treatment. Findings Abstinence rates for bupropion (27.9%) and NRT (24.2%) were not significantly different (odds ratio = 1.21, 95% confidence interval = 0.883–1.67), and the combination rate (24.2%) was similar to that for either treatment alone. There was some evidence that the relative effectiveness of bupropion and NRT differed according to depression (χ2 = 2.86, P = 0.091), with bupropion appearing more beneficial than NRT in those with a history of depression (29.8 versus 18.5%). Several unwanted symptoms were more common with bupropion. Conclusion There is no difference in smoking cessation effectiveness among bupropion, nicotine replacement therapy and their combination when used with behavioural support in clinical practice. There is some evidence that bupropion is more beneficial than nicotine replacement therapy for smokers with a history of depression.

Prevalence of childhood attention deficit hyperactivity disorder in opiate-dependent adults

Background. There is a clear association between childhood attention deficit hyperactivity disorder and substance use disorders in adulthood. Symptoms of attention deficit disorder may also persist into adulthood. The study aimed to determine the prevalence of childhood ADHD in a sample of treatment seeking opiate-dependent adults. Methods. Treatment-seeking opiate-dependent subjects completed the Utah adult ADHD screening test and the self-report early delinquency scale. Results. A total of 15% were “likely” and 49 were “highly likely” to have suffered ADHD in childhood. The averages scores for the delinquency scales were over 6 times those reported from population norms. Conclusion. Symptoms of childhood ADHD is common in adults with opiate dependence. The residual symptoms in adults should be investigated as may be amenable to newer treatments for adult attention deficit disorder.