Borderline personality disorder and aggressive behavior: A study based on the DSM-5 alternative model.

INTRODUCTION: Unplanned reactive aggressive acts are a clinical feature of particular interest in patients with borderline personality disorder (BPD). The early identification of personality traits correlated to aggressive behavior is certainly desirable in BDP populations. This study analyzes a clinical sample of 122 adult outpatients with BPD referred to Adult Mental Health Services of the Department of Mental Health of Bologna, in Italy. METHODS: The study examines the relationship with personality facets of the DSM-5 alternative model for personality disorders (AMPD), Personality Inventory for DSM (PID-5), with respect to the four main components of aggression measured by the Aggression Questionnaire (AQ): hostility, anger, verbal and physical aggression. Using robust regression models, the relationships between PID-5 facets and domains and the aggression components under consideration were identified. RESULTS: Verbal and physical aggression in our sample of BPD outpatients is mainly associated to PID-5 antagonism domain. Physically aggressive behavior is also related to callousness facet. CONCLUSIONS: The traits most consistently associated with aggression were the domain of Antagonism and the facet of Hostility. The study findings highlight the need for clinicians working with individuals with BPD to pay particular attention to traits of hostility, callousness, and hostility to understand aggression.

Specificity profile of venlafaxine and sertraline in major depression: metaregression of double-blind, randomized clinical trials.

Despite the well-known efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of major depressive disorder, there is a lack of indications for each drug in different groups of patients. The aim of this study is to investigate the possible role of clinical sociodemographic factors as moderators of clinical response to venlafaxine (SNRI) and sertraline (SSRI). Research was performed on Medline and EMBASE for randomized control trials in English focused on sertraline and venlafaxine in the treatment of major depressive disorder and 59 studies were included. Clinical efficacy of each treatment was assessed on the basis of Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale. A metaregression analysis was performed to evaluate the role of clinical and sociodemographic factors as moderators of outcome, calculating the effect of each variable with the random-effects method. Gender, ethnicity and duration of depressive episode could have a role in prediction of clinical response to both antidepressants. Venlafaxine seems to have better effects in females and in Caucasian patients. Sertraline seems to be more efficacious in the treatment of females. Both drugs were more efficacious in patients who suffered a shorter episode of illness. Our results could represent an interesting point of view in the perspective of choosing the most suitable therapy based on clinical and social features for each patient. Metaregression is a retrospective analysis, based on the cumulative results of previous studies, so the lack of original data could represent the main limitation in this report and in the interpretation of the results obtained.

Potential benefits of slow titration of paroxetine treatment in an elderly population: eight-week results from a naturalistic setting.

BACKGROUND: Late-life depression, often in association with anxiety, affects approximately 15% of individuals older than 65 years. Selective serotonin reuptake inhibitors are the first-line treatment but could be responsible of an early exacerbation of anxiety, possibly reduced by a very gradual titration of drugs. The main aim of this study is to compare gradual and rapid (standard) titration of paroxetine in an elderly population. METHODS: In a naturalistic setting, 50 elderly (≥60 years old) outpatients with unipolar mood disorder or anxiety disorder were naturalistically assigned to abrupt initiation of 10 mg of paroxetine or to a gradual increase with 2.5 mg on alternate days up to 10 mg in 7 days. Then dosage could be maintained at 10 mg or increased according to clinical response. Primary outcome was efficacy as assessed by the Hamilton Depression Rating Scale (HAM-D) 21, HAM-D symptom subscales (core, psychic anxiety, somatic anxiety cluster), and Hamilton Anxiety Rating Scale changes. Secondary outcome was evaluation of overall dropouts at eighth week and evaluation of most common adverse effects through the global judgment of the Dosage Record and Treatment Emergent Symptom Scale. All data were recorded weekly for the first 8 weeks of treatment (with 1 more evaluation after 3 days from the baseline). RESULTS: Samples were comparable at baseline, with patients in gradual titration showing a higher level of psychic anxiety. During the first 3 days of treatment, a significant worsening in psychic anxiety was observed in patients treated abruptly with 10 mg of paroxetine (difference in HAM-D psychic anxiety subscale from baseline: 110.61% vs 89.38% with rapid and slow titration, respectively; t test P = 0.03). Overall, a significantly greater improvement in depressive and anxious symptoms favored gradual titration (HAM-D core cluster and HAM-D psychic anxiety cluster, respectively, P = 0.014 and P < 0.001, also when controlling for confounders). At the eighth week, significant higher dropouts in patients administered with abrupt dosage was observed (12.00% vs 40.91%, P = 0.02, respectively for slow and rapid titration). CONCLUSIONS: Our results suggest that a gradual titration of paroxetine could avoid the initial treatment anxiety worsening and dropout at the beginning of the treatment.

Prolactin and thyroid hormone levels are associated with suicide attempts in psychiatric patients.

The aim of this study is to evaluate biological factors associated with recent suicidal attempts in a naturalistic sample. A total of 439 patients suffering from major depression disorder (MDD), bipolar disorder (BD) and psychotic disorders (schizophrenia, schizoaffective disorder and psychosis not otherwise specified), who were consecutively assessed in the Emergency Department of an Italian Hospital (January 2008-December 2009), were included. In the whole sample, suicide attempters and non-attempters differed with regard to free triiodothyronine (FT3) and prolactin values only. A univariate general linear model indicated significant effects of sex (F(1;379)=9.29; P=0.002), suicidal status (F(1;379)=4.49; P=0.04) and the interaction between sex and suicidal status (F(1;379)=5.17; P=0.02) on prolactin levels. A multinomial logistic regression model indicated that suicidal attempters were 2.27 times (odds ratio (OR)=0.44; 95% confidence interval (95%CI): 0.23/0.82; P=0.01) less likely to have higher FT3 values than non-attempters; while prolactin values failed to reach statistical significance (OR=0.99; 95%CI: 0.98/1.00; P=0.051). Both prolactin and thyroid hormones may be involved in a complex compensatory mechanism to correct reduced central serotonin activity. Further studies may help in understanding how these findings can be used by clinicians in assessing suicide risk.

Paroxetine for the treatment of depression: a critical update.

INTRODUCTION: A growth in the market for antidepressants, paired with an ever-increasing population affected from depressive disorder, requires a critical re-evaluation of most prescribed antidepressants, in order to provide up-to-date practical prescribing information for clinicians. Paroxetine represents a widely prescribed and reliable antidepressant for the expert clinician, but the latest data do not rank it amongst the most effective and tolerable newer antidepressants. AREAS COVERED: This paper reviews latest data on paroxetine and investigates its clinical efficacy and safety in different groups of patients. EXPERT OPINION: In previous subanalysis and metaregression analysis, paroxetine failed to show clear differences in terms of efficacy across clinical subgroups. Thus, nowadays the pharmacokinetic and pharmacodynamic properties of the molecule are fundamental to guiding its prescription, both for efficacy and tolerability issues, for example, it can have a high impact on sexual function and weight should also be considered at the beginning of treatment. Since prescription is still based mainly on its side-effect profile, newer and more accurate directions for an individualized prescription are needed.

Specificity profile of paroxetine in major depressive disorder: meta-regression of double-blind, randomized clinical trials.

BACKGROUND: Meta-analyses and reviews are powerful tools to inform clinicians on overall effects of their therapeutic choices, but do not provide practically useful clinical profiles for each drug optimal efficacy. Therefore clinicians in everyday practice have to rely mainly on personal or anecdotic experience. The aim of present study was to define the most suitable sociodemographic and disease-related profile for the use of paroxetine as an antidepressant treatment. METHODS: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched for randomized controlled trials (RCT) in English focused on "paroxetine" and "depressive disorder" or "major depression". We also considered reviews and meta-analyses focusing on paroxetine. Fifty-five total unique RCTs were included and sociodemographic and clinical data as moderator of efficacy measures (standardized mean difference based on Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale) were investigated via meta-regression analysis. RESULTS: Paroxetine was significantly characterized by better response in females and in Caucasians, whilst for patients who have been ill for a longer time before treatment, the smaller was the antidepressant effect. Other disease-related variables were not found to be significant moderators in clinical outcome. LIMITATIONS: Meta-regression may lack sufficient sensibility to detect specific subtle features, so a failure to find significant effect is not definitive evidence of a lack of effect. CONCLUSIONS: Our results, though significant, were generally observed with small estimate values, their clinical relevance is subtle since each feature is expected to influence marginally the whole outcome, and probably a more pronounced effect could result only by analyzing very large samples.

Pharmacogenetics of antidepressant response.

Personalized medicine - the adaptation of therapies based on an individual's genetic and molecular profile - is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

Influence of neuronal cell adhesion molecule (NCAM1) variants on suicidal behaviour and correlated traits.

Suicide is a public health problem all around the world. Family studies showed a strong heritability but, to date, few genetic data are available. Thus, in the present study we investigated whether a panel of single nucleotide polymorphisms (SNPs) in neuronal cell adhesion molecule 1 (NCAM) 1 was associated with suicidal behaviour as well as specific traits related to suicide. A total of two hundred and fifty-nine individuals with a positive history of suicidal behaviour and 312 healthy subjects were enrolled in the study. Rs2301228, rs1884, rs1245113, rs1369816, rs2196456 and rs584427 in NCAM1 were genotyped. No marker was significantly associated with suicidal behaviour vs. controls or with sub-types of attempted vs. completed, violent vs. non-violent, impulsive vs. non-impulsive suicide. Nonetheless rs1884 and rs2196456 SNPs were both marginally associated with the trait "inhibition of aggressiveness" in suicide attempters. Even though the investigated SNPs in NCAM1 do not seem to be directly associated with suicidal behaviour, our results could suggest that SNP variants in NCAM1 may impact on related traits, particularly by mediating inhibition of aggressiveness. However, independent studies are needed to validate these results.

Predictors of early worsening after switch to aripiprazole: a randomized, controlled, open-label study.

BACKGROUND: Despite the increasing evidence relating to strategies for switching between different antipsychotics, little evidence is available about predictors of improvement or worsening while switching. In a previous study, we compared different options for switching to aripiprazole and found that patients with schizophrenia switched to aripiprazole with immediate discontinuation of the previous antipsychotic showed an increase in symptom severity after 1 week. OBJECTIVE: To identify predictors of worsening in the first 4 weeks after the switch to aripiprazole in partial non-responders to previous treatments. METHODS: This was a 12-week randomized, controlled, open-label study that was carried out in the Department of Psychiatry of the Catholic University of Korea, Seoul, Korea. The study included 77 patients with schizophrenia whose symptoms were not optimally controlled and/or who did not tolerate their current antipsychotic medications well. Patients were randomly assigned to one of three different strategies for switching to aripiprazole 10 mg, i.e.: (i) simultaneous discontinuation of the current antipsychotic; (ii) tapering off the current antipsychotic over 4 weeks with half the dose after the first 2 weeks; or (iii) tapering off the current antipsychotic over 4 weeks after maintenance of the current dose for 2 weeks. The main outcome measure was the difference in Brief Psychiatric Rating Scale (BPRS) scores from baseline to weeks 1, 2 and 4. RESULTS: Baseline severity of disease, as measured by the Clinical Global Impression-Severity Scale, BPRS and Schedule for the Assessment of Negative Symptoms, significantly predicted worsening at weeks 1, 2 and 4. Specifically, lesser disease severity at baseline significantly predicted worsening after switching to aripiprazole. CONCLUSION: Patients with relatively mild illness severity might be more susceptible to early worsening of symptoms when switched to aripiprazole. However, the limitations of the present study, including a small sample size, absence of a control group designed to control for nonspecific factors such as regression to the mean, and implementation of a switching strategy that included only aripiprazole, mean the present findings should be considered with caution and further research is needed.