Paz García-Portilla

New treatment guidelines for acute bipolar mania: A critical review

A number of treatment guidelines for bipolar disorder have been published and updated in the last few years. They are aimed at providing a synthesis of the best available scientific knowledge, and their application to every-day work should be helpful to clinicians. The aim of this report is to critically review recent guidelines focusing on the treatment of manic/hypomanic and mixed episodes. Guidelines are quite heterogeneous in methodology and conclusions, but they all agree that the treatment of manic/hypomanic and mixed episodes should generally be initiated with a medication such as lithium (Li), valproate (VPA) or atypical antipsychotics (AAP), including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone as monotherapy. All guidelines agree on stopping ongoing antidepressant medication during mania. Combination therapy including Li or VPA with an AAP is suggested usually as second-line choice, sometimes as first-choice treatment for severe mania. Carbamazepine is mostly suggested as second line and not recommended in combination. Other antiepileptic drugs are not recommended for the treatment of mania, although lamotrigine may be maintained if it was prescribed previously for the prevention of depressive episodes. Main sources of discrepancies among guidelines include benefit-risk ratio issues (how much priority is given to efficacy over safety and tolerability), starting with combination versus monotherapy, and how to deal with treatments which are more experience-based than evidence-based (i.e.: electroconvulsive therapy).

Quality of life measures in schizophrenia

The recognition of the importance of evaluating the quality of life of patients with schizophrenia highlighted the importance of developing appropriate instruments. In this paper we review the available quality of life instruments focusing on their conceptual framework, structure, administration and psychometric properties. First, we address the generic instruments that have been validated for schizophrenic populations, namely the World Health Organization Quality of Life Assessment (WHOQOL), the Medical Outcome Study (MOS) 36-Item Short-Form Health Survey (SF-36) and the EuroQoL-5 Dimensions (EQ-5D). Then, we focus on instruments that have been specifically developed for patients with schizophrenia and other or severe mentally illness such as the Quality of Life Scale (QLS), the Quality of Life Interview (QoLI), the Lancashire Quality of Life Profile (LQoLP), the Sevilla Quality of Life Questionnaire (SQLQ), the Personal Evaluation of Transitions in Treatment (PETIT), and the Quality of Life Questionnaire in Schizophrenia (S-QoL).

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.

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.

Is attempted suicide different in adolescent and adults

Attempted suicide may be a different phenomenon in adolescents than in adults. To our knowledge, direct comparisons between these two populations are very scarce. The aim of this study is to analyze the differences between adolescents and adults in methods of attempted suicide, accompanying certainty of death, and intentionality. All cases admitted to one adult (n=173) and one adolescent (n=104) inpatient unit who attempted suicide in the period from January 2003 through October 2005 were included in a prospective, common, national register, with data on methods, circumstances, and intentionality. The methodology followed that of the WHO/Euro Multicenter Study on Parasuicide. A stratified analysis was performed using the Mantel-Haenszel procedure in order to control for the effects of gender and diagnosis. Adolescents used significantly more over-the-counter medicines. Adults were significantly more certain of the possible fatal outcome of their attempt and had a significantly more severe intention when harming themselves. Individuals appear to use the methods that are available to them to attempt suicide. Adolescents may display more impulsive and less lethal directed behavior than adults or, alternatively, they are more frequently admitted for less severe attempts.

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.

Association study of the interleukin-1 gene complex and tumor necrosis factor alpha gene with suicide attempts

To investigate the association between four functional polymorphisms in interleukin-1 (IL-1) [IL-1&agr; −889 C/T, IL-1&bgr; +3953 C/T, IL-1RA (86 bp)n] and tumor necrosis factor alpha (TNF&agr;) (−308A/G) genes and suicide attempts. Distribution of the aforesaid polymorphisms was analyzed in 193 suicide attempters compared with 420 unrelated healthy controls from Asturias (Northern Spain). Genotypes were determined using standard methods. No significant differences were found in genotype or in allelic distribution of IL-1&agr;, IL-1&bgr;, IL-1RA, or TNF&agr; gene polymorphisms. No relationship was found between genotypes and the impulsivity of the suicide attempt. Estimated IL-1 haplotype frequencies were similar in both groups (likelihood ratio test=13.26, df=14, P=0.506). Our data do not suggest that genetically determined changes in the IL-1 or TNF&agr; genes confer increased susceptibility to suicidal behavior.

Protocolo de estudio de un programa para la prevención de la recurrencia del comportamiento suicida basado en el manejo de casos (PSyMAC)

INTRODUCTION Prevention of suicidal behaviour is a public health priority in the European Union. A previous suicide attempt is the best risk predictor for future attempts, as well as completed suicides. The primary aim of this article is to describe a controlled study protocol designed for prevention of recurrent suicidal behaviour that proposes case management, and includes a psychoeducation program, as compared with the standard intervention (PSyMAC). METHODS Patients admitted from January 2011 to June 2013 to the emergency room of the Hospital Universitario Central de Asturias were evaluated using a protocol including sociodemographic, psychiatric, and psychosocial assessment. Patients were randomly assigned to either a group receiving continuous case management including participation in a psychoeducation program (experimental group), or a control group receiving standard care. The primary objective is to examine whether or not the period of time until recurrent suicidal behaviour in the experimental group is significantly different from that of the control group. CONCLUSION PSyMAC proposes low cost and easily adaptable interventions to the usual clinical setting that can help to compensate the shortcoming of specific action protocols and suicidal behaviour prevention programs in our country. The evaluation of PSyMAC results will determine their real effectivity as a case-magament program to reduce suicidal risk.

Predictors of posttreatment drinking outcomes in patients with alcohol dependence.

Aim: This cohort study examined how predictors of alcohol dependence treatment outcomes work together over time by comparing pretreatment and posttreatment predictors. Methods: A sample of 274 alcohol-dependent patients was recruited and assessed at baseline, 6 months after treatment initiation (end of the active intervention phase), and 18 months after treatment initiation (end of the 12-month research follow-up phase). At each assessment point, the participants completed a battery of standardized tests [European Addiction Severity Index (EuropASI), Obsessive Compulsive Drinking Scale (OCDS), Alcohol Timeline Followback (TLFB), Fagerström, and International Personality Disorder Examination (IPDE)] that measured symptom severity and consequences; biological markers of alcohol consumption were also tested at each assessment point. A sequential strategy with univariate and multivariate analyses was used to identify how pretreatment and posttreatment predictors influence outcomes up to 1 year after treatment. Results: Pretreatment variables had less predictive power than posttreatment ones. OCDS scores and biological markers of alcohol consumption were the most significant variables for the prediction of posttreatment outcomes. Prior pharmacotherapy treatment and relapse prevention interventions were also associated with posttreatment outcomes. Conclusions: The findings highlight the positive impact of pharmacotherapy during the first 6 months after treatment initiation and of relapse prevention during the first year after treatment and how posttreatment predictors are more important than pretreatment predictors.