Gerardo Flórez

Using Topiramate or Naltrexone for the Treatment of Alcohol-Dependent Patients

BACKGROUND To compare topiramate versus naltrexone in the treatment of alcohol dependence. METHODS A 6-month naturalistic, randomized and open-label, trial of topiramate versus naltrexone, with assessments at enrollment and after 3 and 6 months of treatment. The setting was an outpatient alcohol clinic. One hundred and two alcohol-dependent patients who had been drinking heavily during the past month were included. Two randomized groups were created. In one, naltrexone was used as the therapeutic agent and, in the other, topiramate was chosen as the therapeutic agent. Both groups received psychological relapse prevention therapy. Outcome was measured using tools that assessed alcohol intake, cravings, disability, and quality of life; changes in biomarkers of alcohol intake were also used. With all the data, a secondary composite measure was created in order to assess each patients global alcohol intake and its consequences. RESULTS Both groups showed substantial reduction in their drinking. Naltrexone patients had higher nicotine consumption throughout the study. Topiramate was better at reducing alcohol-related cravings throughout the study. Both treatments had a similar mean cost throughout the study. CONCLUSIONS Both topiramate and naltrexone were efficacious in the treatment of alcohol dependence, and the treatment costs were similar. There is a trend for topiramate to be superior to naltrexone on critical measures of drinking; however, the study did not have adequate statistical power to establish this fact.

Association study between obsessive-compulsive disorder and serotonergic candidate genes.

BACKGROUND To date, research examining the relationship between serotonergic genes and obsessive-compulsive disorder (OCD) has yielded conflicting results. The purpose of this study is to investigate the association between four serotonergic polymorphisms (STin2 VNTR and 5-HTTLPR of the SLC6A4 gene, and A-1438G (rs6311) and T102C (rs6313) of the HTR2A gene) and OCD. METHODS 99 OCD patients, 456 non-OCD psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS All groups showed Hardy-Weinberg equilibrium for the analyzed genetic variability. A-1438G and T102C polymorphisms were in complete linkage disequilibrium. OCD patients showed an excess of STin2.12 carriers (12/12, 12/10, and 12/9 genotypes) compared with healthy controls (chi(2) (1)=7.21, corrected p=0.021; OR=3.38, 95% CI=1.32-8.62) and non-OCD psychiatric patients (chi(2) (1)=6.70, corrected p=0.030; OR=3.24, 95% CI=1.27-8.26). However, no differences were found between non-OCD patients and healthy controls (chi(2) (1)=0.05, corrected p>1; OR=1.04, 95% CI=0.72-1.51). No significant differences were found with respect to A-1438G and 5-HTTLPR polymorphisms. CONCLUSIONS Our data provide supporting evidence of an association between the STin2 VNTR polymorphism of the SLC6A4 gene and OCD.

Topiramate for the Treatment of Alcohol Dependence: Comparison with Naltrexone

Background: A 6-month naturalistic, randomized and open-label, trial of topiramate versus naltrexone was conducted, with assessments at enrollment and after 3 and 6 months of treatment. 182 alcohol-dependent patients who had been drinking heavily during the past month were included. Methods:Outcome was measured using tools that assessed alcohol intake, cravings, disability, and quality of life; changes in biomarkers of alcohol intake were also used. Results: At the 6-month evaluation, patients taking topiramate had significantly lower scores on the OCDS (all subscales), the EuropASI (medical, alcohol, family/social, and psychiatric) and the WHO/DAS (employment/social). More patients taking topiramate remained in the abstinence group and the moderate drinking without problems group. Conclusions: Topiramate at a mean dose of 200 mg/day was better than naltrexone at a mean dose of 50 mg/day at reducing alcohol intake and cravings throughout the study.

Differential role of serotonergic polymorphisms in alcohol and heroin dependence

BACKGROUND Twin studies suggest that genetic factors account for 40-60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence. METHODS 165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of -1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI)=1.98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df)=10.21 (4), p=0.037). The association of -1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups. CONCLUSIONS Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.

Association Between the Stin2 VNTR Polymorphism of the Serotonin Transporter Gene and Treatment Outcome in Alcohol-Dependent Patients

AIMS The aim of this study was to investigate the potential association between functional polymorphisms of dopaminergic [dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3) and dopamine transporter (SLC6A3)] and serotonergic [serotonin 2A receptor (HTR2A) and serotonin transporter (SLC6A4)] genes and treatment outcome in alcohol-dependent patients. METHODS A total of 90 Spanish Caucasian alcohol-dependent outpatients (ICD-10 criteria) were enrolled in the study. The association between genotypes and drinking outcomes was measured over 6 months of treatment. Biomarkers of alcohol consumption, as well as alcohol consumption and its consequences, craving, disability and quality of life, were assessed. Based on those measures, we created a composite secondary measure to globally assess treatment outcome in alcoholism. RESULTS No association was found between DRD2, DRD3, SLC6A3 or HTR2A gene variants and treatment outcome. However, SLC6A4 STin2 12/12 carriers showed poor 6-month time point treatment outcome [32.8% in the good outcome group versus 64.0% in the poor outcome group, chi(2) (df) = 7.20 (1), corrected P = 0.042, OR (95% CI) = 0.27 (0.10-0.72)]. Nevertheless, independent analysis of each treatment group reveals that the excess of 12/12 carriers in the poor outcome group was only found in the naltrexone-treated group [24.1% versus 64.7% chi(2) (df) = 7.41 (1), corrected P = 0.042, OR (95% CI) = 0.17 (0.05-0.64)]. In the whole sample, the L-10 repeats haplotype (5-HTTLPR-STin2 VNTR) is associated with good outcome (LRT = 3.88, df = 1, P = 0.049). CONCLUSIONS Our findings suggest that functional polymorphism of the SLC6A4 gene may have an influence on treatment outcome in alcohol-dependent patients.

Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

OBJECTIVE To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior. SUBJECTS AND METHODS 227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS There were no differences in genotype frequencies between the three groups. The -1438A/G [χ(2) (df)=9.80 (2), uncorrected p=0.007] and IL-1α -889C/T [χ(2) (df)=8.76 (2), uncorrected p=0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of -1438G/G or IL-1α -889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df)=6.84 (2), p=0.033] and between the polymorphisms APOE and IL-1RA (86bp)(n) [LRT (df)=12.21 (4), p=0.016] in relation to suicide attempt lethality. CONCLUSION These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.

Polymorphisms of the IL‐1 Gene Complex Are Associated With Alcohol Dependence in Spanish Caucasians: Data From an Association Study

BACKGROUND There is growing evidence for involvement of pro-inflammatory cytokines in alcohol dependence. The aim of this study was to investigate whether 4 functionally relevant polymorphisms of the interleukin-1 (IL-1) and tumor necrosis factor-alpha genes were associated with alcohol dependence and with measures of clinical severity and treatment outcome. METHODS Two hundred alcohol-dependent (AD) patients and 420 healthy controls from the same Spanish Caucasian population were genotyped using standard methods. Baseline and 6-month assessments included alcohol intake, addiction severity, and biomarkers of alcohol intake. RESULTS Alcohol-dependent patients showed an excess of IL-1alpha-889 C/T [50.8% vs. 39.3%, chi(2) (df) = 7.30 (2), uncorrected p = 0.026, corrected p = 0.104] and IL-1RA (86 bp)(n) A1/A1 genotypes [64.8% vs. 50.8%, chi(2) (df) = 12.65 (3), corrected p = 0.020]. The A1/A1 excess was associated with alcohol dependence only in men [69.9% vs. 49.5%, chi(2) (df) = 15.72 (2), corrected p < 0.001]. Six-month clinical and hematological outcome measures did not vary by genotype of the 4 polymorphisms. Haplotype analysis revealed an excess of the IL-1alpha-889 C/IL-1beta +3953 C/IL-1RA A2 haplotype in the control group compared with AD patients [20.0% vs. 14.1%, chi(2) (df) = 7.25 (1), p = 0.007; odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.46-0.89] and in the abstainers after 6 months of treatment compared with nonabstinent patients [14.7% vs. 6.2%, chi(2) (df) = 5.65 (1), p = 0.017; OR = 2.56, 95% CI = 1.15-5.62]. CONCLUSIONS Our findings provide further tentative evidence of the role of IL-1 in alcohol dependence as well as evidence that the nature of the associations may be direct, gender-specific, or involve haplotype effects. However, findings from single association studies constitute tentative knowledge and must be interpreted carefully and precise replication is required.

Psychiatric Comorbidity in Patients from the Addictive Disorders Assistance Units of Galicia: The COPSIAD Study

The objective of this study is to assess the prevalence of psychiatric comorbidity in patients under treatment within the addictive disorders assistance units of Galicia (Spain). Material and Methods A total of 64 healthcare professionals performed clinical diagnosis of mental disorders (on DSM IV-TR criteria) in 2300 patients treated throughout March 2010 in 21 addictive disorders assistance units. Results 56.3% of patients with substance abuse/dependency also showed some other mental disorder, 42.2% of patients suffering from at least an Axis I condition and 20.2% from some Axis II condition. Mood and anxiety disorders and borderline and antisocial personality disorders were the most frequent disorders in both axes. Conclusions A high comorbidity was found between mental and substance use disorders (SUD) in patients seen at the addictive disorders assistance units of Galicia.

Impulsivity, implicit attitudes and explicit cognitions, and alcohol dependence as predictors of pathological gambling.

Impulsivity, implicit attitudes and explicit cognitions regarding gambling, and alcohol abuse have been pointed out by past research as significant contributors to the development and maintenance of gambling disorders. In this study, we tested the relationship among these contributors and pathological gambling. Forty-four pathological gamblers (DSM-5 criteria), of whom 23 were active gamblers and 17 were alcohol dependent, were compared with 100 controls, consisting of patients with a lifetime history of alcohol use disorder in remission for at least 2 years. The following protocol was used for the comparison: National Opinion Research Center Diagnostic Screen for Gambling Disorders, Barratt Impulsiveness Scale Version 11 (BIS-11), Gambling Related Cognitions Scale (GRCS), Obsessive Compulsive Drinking Scale, Alcohol Use Disorders Identification Test, and Gambling Implicit Association Test (IAT). Impulsivity (BIS-11) and changes in implicit attitudes (IAT) were able to discriminate between pathological gamblers and controls, the latter being less impulsive and having fewer implicit attitudes towards gambling. Cognitive impulsivity (BIS-11), explicit gambling cognitions (GRCS), and alcohol dependence were able to discriminate between active and non-active pathological gamblers, the latter having less cognitive impulsivity and less explicit gambling cognitions and alcohol dependence. Using these simple tools can help clinicians in the assessment of pathological gambling.

Tabaco y rendimiento cognitivo en pacientes con esquizofrenia: diseño del estudio COGNICO

People with schizophrenia constitute a substantial part of the people who still smoke. Regarding cognitive performance, the self-medication hypothesis states that patients smoke to improve their cognitive deficits based on the stimulating effects of nicotine. The aim of this paper is to describe in detail the methodology used in the COGNICO study. A quasi-experimental, observational, prospective, multicenter study with follow-ups over 18 months was conducted in three cities in northern Spain (Oviedo, Ourense and Santiago de Compostela). A total of 81 outpatient smokers with schizophrenia were recruited with a mean age 43.35 years (SD = 8.83), 72.8% of them male. They were assigned to 3 groups: a) control group (smokers); b) patients who quit smoking using nicotine patches; c) patients who quit smoking with Varenicline. The MATRICS neuropsychological battery was applied as a primary measure. In addition, a comprehensive assessment of patients was performed, including the number of cigarettes per day, physical and psychological dependence on nicotine and CO expired. Clinical evaluation (PANSS, HDRS, CGI, C-SSRS), anthropometric measurements and vital signs assessment was also performed. The aim is to identify the relationship between the pattern of tobacco use and cognitive performance by comparing scores on the neuropsychological battery MATRICS during the follow-up periods (3, 6, 12 and 18months). The importance of this study lies in addressing a topical issue often ignored by clinicians: the unacceptably high rates of tobacco use in patients with severe mental disorders.