Neuroendocrine assessment of serotonergic, dopaminergic, and noradrenergic functions in alcohol-dependent individuals

Background: Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol‐dependent individual. Methods: Alcohol‐dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2‐adrenoceptor function by GH response to clonidine (CLON). Results: In the alcohol‐dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO‐GH and CLON‐GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol‐dependent individuals than controls (43% vs. 6% respectively). Conclusions: The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long‐term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol‐dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.     

A double-blind, placebo-controlled trial to assess the efficacy of quetiapine fumarate XR in very heavy-drinking alcohol-dependent patients

Background: Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol‐dependent population of very heavy drinkers. Methods: In this double‐blind, placebo‐controlled trial, 224 alcohol‐dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization. Results: No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy‐drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%). Conclusions: This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy‐drinking alcohol‐dependent patients.     

Post-treatment outcomes in a double-blind, randomized trial of sertraline for alcohol dependence

Background: Pharmacotherapy studies in alcohol dependence (AD) are generally of short duration and do not include post‐treatment follow‐up. We examined the durability of treatment effects in a placebo‐controlled trial of sertraline for AD. Methods: As previously reported, patients received 12 weeks of treatment with sertraline (n = 63) or placebo (n = 71), followed by assessments at 3 and 6 months post‐treatment ( Kranzler et al., 2011 , J Clin Psychopharmacol 31:22–30). We examined the main and interaction effects with time of 3 between‐subject factors (medication group, age of onset of AD [late‐onset alcoholics, LOAs, vs. early‐onset alcoholics, EOAs], and the tri‐allelic 5‐HTTLPR genotype) on drinking days (DDs) and heavy drinking days (HDDs). Results: The medication group effect, which was significant during treatment, remained significant during the 3‐month follow‐up period for L’/L’ LOAs, with the sertraline group having fewer DDs than the placebo group (p = 0.027). However, the medication group effect seen in L’/L’ EOAs during treatment was no longer significant (p = 0.48). There were no significant effects in S’ carriers at the 3‐month follow‐up visit, or in either genotype group at the 6‐month follow‐up. Conclusions: The beneficial effects of sertraline observed in LOAs during treatment persisted during the 3‐month post‐treatment period. Additional studies are needed to validate these pharmacogenetic findings, which together with the effects seen during active treatment support the use of sertraline only in LOAs.     

Utbredelsen av stoffbruk hos unge menn i Norge i 1972–1973

Two methods of providing an educational intervention for families of patients with schizophrenia in Finland were compared. The aims of the intervention were to improve relatives' level of knowledge about the illness, and change the level of expressed emotion (EE), objective burden and psychological distress. Sixty-nine persons participated in the oral presentation groups comprising eight sessions and 128 persons participated in the video education comprising six sessions. The education led to significant knowledge gains and to an increase in the psychological well-being of the participants, but there were no significant changes in objective burden or EE status after intervention. Furthermore, there was only one difference between the two methods of information delivery. The participants in the video groups felt more often that the lessons were useful to them than did the participants in the oral presentation groups. The evidence suggests that brief educational intervention can yield significant benefits in meeting the needs of family members. Better designed, randomized studies investigating the efficacy of brief educational interventions are needed.     

Methylphenidate vs. resperidone in treatment of methamphetamine dependence: A clinical trial

Background and aims

Currently, there is no widely accepted evidence-based pharmacotherapy regime for the treatment of psychostimulant dependence. Yet, different pharmacological approaches have been tried in the treatment of MA addiction. The present study was conducted to compare efficiency of methylphenidate which is relatively easily accessible in our country, with resperidone for this purpose.

Methods

Eighty-six patients with MA dependence according to criteria defined by DSM IV-TR were divided into two groups. Patients in group R were given oral resperidone 1 mg daily for 1 week; then 2 mg daily in a divided dose for 3 weeks. Patients in group M were given oral methylphenidate 10 mg daily for 2 weeks, 7.5 mg daily for 1 week, then 5 mg daily for 1 week. They were evaluated for drug craving, psychological, neurologic and somatic symptoms at the start and end of the study.

Findings

Both drugs were useful for lowering drug craving in patients; however resperidone was more effective (6.31 ± 8.31 vs.19.6 ± 12.45 cravings per week, respectively). The effects of resperidone were more notable in lowering frequency and intensity of psychiatric, neurologic, cardiac and somatic symptoms of the patients after discontinuation of MA abuse; however methylphenidate was effective too; though with a lower potency.

Conclusion

The present study confirmed that both methylphenidate and resperidone can successfully be used for treatment of MA dependence, in order to reduce drug craving and psychological, neurologic, and somatic problems in patients. However, the efficacy of methylphenidate was estimated to be less than that of resperidone for this purpose.     

Factors associated with weight changes in successful quitters participating in a smoking cessation program

Objective

To identify possible predictors of post-cessation weight gain in smoking abstainers.

Patients and methods

A sample of 607 successful abstainers seen at the Centre for Tobacco-Dependent in Prague, Czech Republic, between 2005 and 2010, was included in this analysis. This sample was followed up for 1 year and included 47.9% women (N = 291) with the mean age of 48 years (18–85).

Findings

Post-cessation weight gain occurred in 88.6% of the 607 abstainers. The mean weight gain after one year post-quit was 5.1 kg (95% confidence interval 4.7–5.5 kg). Baseline characteristics associated with increased weight gain included a higher baseline smoking rate (p < 0.001), more severe cigarette dependence (p = 0.003), less physical activity (p = 0.008), and a report of increased appetite on the baseline assessment of withdrawal symptoms (p < 0.001).

Conclusions

Smokers who are more dependent and have minimal physical activity are at increased risk for post-cessation weight gain. For these smokers, incorporating interventions targeting the weight issue into tobacco dependence treatment is recommended. Further research should be done to identify reasons for this important quitting complication.