The effect of paliperidone palmitate long-acting injectable (PP-LAI) on "non-core" symptoms of schizophrenia: a retrospective, collaborative, multicenter study in the "real world" everyday clinical practice.

BACKGROUND: Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability. AIM: The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice. RESULTS: Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced. DISCUSSION: The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life. CONCLUSIONS: PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings.

Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases.

Cariprazine is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to the D3 receptor, antagonism of 5HT2B receptors, and partial agonism of 5HT1A. Currently, cariprazine has shown clinical efficacy in patients with schizophrenia and with bipolar disorder, as well as adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. In the present case series, we report on two patients with treatment-resistant schizophrenia and partial response to clozapine who benefit from combination with cariprazine. The effects of cariprazine combination were remarkable also concerning the adverse metabolic effects of clozapine.

Religious Coping, Hopelessness, and Suicide Ideation in Subjects with First-Episode Major Depression: An Exploratory Study in the Real World Clinical Practice.

BACKGROUND: This study aimed to evaluate the potential relationships between religious coping, hopelessness, and suicide ideation in adult outpatients with the first episode of major depressive disorder (MDD). METHODS: Ninety-four adult outpatients with MDD were assessed through the Hamilton Depression Rating Scale (HAM-D), the Beck Hopelessness Scale (BHS), and the Scale of Suicide Ideation (SSI). Religious coping was assessed with the Italian version of the Brief RCOPE scale, consisting of seven positive coping items (PosCop) and seven negative coping items (NegCop). RESULTS: The results showed that the Brief RCOPE PosCop scale exhibited a strong inverse correlation with HAM-D, BHS, and SSI, whereas HAM-D and BHS were positively correlated with SSI. Brief RCOPE NegCop scores were positively correlated only with SSI. Regression analysis with SSI as the dependent variable showed that higher Brief RCOPE PosCop scores were associated with lower suicide ideation, whereas higher HAM-D and BHS scores were associated with higher suicide ideation. CONCLUSION: Positive religious coping may be a protective factor against the development of suicide ideation, perhaps counteracting the severity of depressive symptoms and hopelessness. The evaluation of religious coping should be performed in all subjects with MDD in everyday clinical practice. However, this study was preliminary, and limitations must be considered.

Adjunctive vortioxetine for SSRI-resistant major depressive disorder: a real-world chart review study

Objective: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. Methods: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression ‐ Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). Results: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). Conclusions: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

Adjunctive vortioxetine for SSRI-resistant major depressive disorder: a "real-world" chart review study.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. METHODS: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression - Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). RESULTS: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). CONCLUSIONS: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

Alexithymia, suicide ideation, affective temperaments and homocysteine levels in drug naïve patients with post-traumatic stress disorder: an exploratory study in the everyday 'real world' clinical practice.

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday 'real world' clinical setting.Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured.Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 'Difficulty in Identifying Feelings' dimension was associated with higher SSI scores.Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. KeypointsPatients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation.The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD.Homocysteine did not correlate with any studied variables.This study was exploratory and cross-sectional: further larger and prospective studies are needed.

The FDA "Black Box" Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits?

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications.

Alexithymia, Suicide Ideation and Homocysteine Levels in Drug Naïve Patients with Major Depression: A Study in the "Real World" Clinical Practice

Objective: : This study was performed to elucidate relationships between alexithymia, suicide ideation and homocysteine levels in drug-naïve outpatients with major depressive disorder (MDD). Methods: : Sixty seven outpatients with MDD with melancholic features were evaluated by the means of the Hamilton Depression Rating Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation, and homocysteine levels. Results: : Alexithymic subjects showed higher scores on all scales and higher homocysteine levels. Regression analysis shown higher homocysteine levels and TAS-20' "Difficulty in Describing Feelings" dimension, in turn being associated with higher suicide ideation. Conclusion: : In conclusion, alexithymic MDD outpatients may characterize for homocysteine dysregulation that may be linked to suicide ideation, regardless depression' severity. However, study limitations are discussed and must be considered.

Clozapine-related Sudden Pericarditis in a Patient Taking Long Acting Aripiprazole and Valproate: A Case Report.

Clozapine may be associated with cardiovascular adverse effects including QTc prolongation and, more rarely, with myocarditis and pericarditis. Although rare, these latter cardiovascular adverse effects may be life-threatening and must be immediately recognized and treated. Several cases of clozapine related-pericarditis have been described and often it has a subtle and insidious onset with symptoms that may be often misdiagnosed with psychiatric manifestations (e.g. anxiety, panic or somatization) leading to a delayed correct diagnosis with potential fatal consequences. In the present report we describe the case of a 27-year-old girl with schizoaffective disorder taking long acting aripiprazole and valproate who developed a sudden onset clozapine-related pericarditis during titration phase that resolved with immediate clozapine discontinuation and indomethacin administration. We underline the importance of an early diagnosis of clozapine-related pericarditis and the need to have monitoring protocols to prevent this potentially fatal adverse effect especially when polypharmacy is administered to patients taking clozapine.

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A Systematic Review.

BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible for schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well defined. Accordingly, the role of an acute inflammatory phase protein, the C-reactive protein (CRP) has been recently investigated. OBJECTIVE: The objective of the present study is to evaluate how PCR may represent a biomarker in schizophrenia, i.e. correlated with illness phases and/or clinical manifestation and/or psychopathological severity. METHODS: A systematic review was here carried out by searching the following keywords ((C-reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics 'PCR' and 'Schizophrenia', by using MESH terms. RESULTS: An immune dysfunction and inflammation have been described amongst schizophrenic patients. Findings reported elevated CRP levels in schizophrenia, mainly correlated with the severity of illness and during the recrudescent phase. CRP levels are higher when catatonic features, negative symptomatology and aggressiveness are associated. CRP levels appeared not to be related to suicidal behaviour and ideation. CONCLUSION: CRP and its blood levels have been reported higher amongst schizophrenic patients, by suggesting a role of inflammation in the pathogenesis of schizophrenia. Further studies are needed to better understand if CRP may be considered a biomarker in schizophrenia.

The Effects of Paleoclimatic Events on Mediterranean Trout: Preliminary Evidences from Ancient DNA.

In this pilot study for the first time, ancient DNA has been extracted from bone remains of Salmo trutta. These samples were from a stratigraphic succession located in a coastal cave of Calabria (southern Italy) inhabited by humans from upper Palaeolithic to historical times. Seven pairs of primers were used to PCR-amplify and sequence from 128 to 410 bp of the mtDNA control region of eleven samples. Three haplotypes were observed: two (ADcs-1 and MEcs-1) already described in rivers from the Italian peninsula; one (ATcs-33) belonging to the southern Atlantic clade of the AT Salmo trutta mtDNA lineage (sensu Bernatchez). The prehistoric occurrence of this latter haplotype in the water courses of the Italian peninsula has been detected for the first time in this study. Finally, we observed a correspondence between frequency of trout remains and variation in haplotype diversity that we related with ecological and demographic changes resulting from a period of rapid cooling known as the Younger Dryas.

Inflammatory markers and suicidal attempts in depressed patients: A review.

Major depressive disorder is a chronic and invalidating psychiatric illness and is associated with a greater risk of suicidal behaviors. In recent decades many data have supported a biological link between depressive states and inflammation. Pro-inflammatory cytokines have been found to rise, first of all TNF-α and IL-6. Suicidal behaviors have been consistently associated with increased levels of IL-6 and decreased levels of IL-2. The aim of this review is to investigate the relationship between inflammatory markers in depressed patients with or without suicidal attempts compared to healthy controls.

Agomelatine beyond borders: current evidences of its efficacy in disorders other than major depression.

Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine's antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression.

Alexithymia, responsibility attitudes and suicide ideation among outpatients with obsessive-compulsive disorder: an exploratory study.

AIMS: Obsessive-compulsive disorder (OCD) is psychiatric disorder with a significant suicide risk, and the presence of alexithymia may increase this risk. As several studies attribute an important role, in OCD, to responsibility, the aims of this study were to evaluate possible clinical differences between patients positive or not for alexithymia concerning disorder severity, responsibility attitudes and suicide ideation and investigate which variables were associated with increased suicide ideation. METHODS: 104 adult outpatients with OCD were recruited. Alexithymia was measured with Toronto Alexithymia Scale (TAS-20), attitude about responsibility was tested with Responsibility Attitude Scale (RAS), suicide ideation was assessed with Scale of Suicide Ideation (SSI) and depressive symptoms were evaluated with Montgomery Åsberg Depression Rating Scale (MADRS). Score of item #11 on the Y-BOCS was considered as a measure of insight. RESULTS: Patients positive for alexithymia showed higher responsibility attitudes and more severe suicide ideation. In a blockwise regression model, the presence of lower insight, higher RAS scores and difficulty in identifying feelings dimension of TAS-20 were associated with higher SSI scores. CONCLUSIONS: OCD patients with alexithymia may show higher disorder severity, lower insight and inflated responsibility, all related to suicide ideation, independently from depressive symptoms. Implications were discussed and study limitations considered and reported.

The world's biogeographical regions revisited: global patterns of endemism in Tipulidae (Diptera).

This paper explores the distributional data of 4,224 Tipulidae (Insecta: Diptera) species to search for endemism patterns in a worldwide scale and to test the extent to which the global patterns of endemism of the group fit into previously proposed regionalization schemes, particularly Wallace's system and recent revisions of it. Large scale areas of endemism are assessed using the grid-based method implemented in VNDM. VNDM depends on the prior definition of the grid size for analysis, but a criterion for choosing beforehand a particular grid size is not clear. The same holds for the choice of the level of similarity in species composition selected for the calculation of consensus areas. In our study, we developed a methodological approach that helped defining objective criteria for choosing suitable values for these critical variables. Large-scale areas of endemism around the globe are identified and ranked according to endemicity levels: 1--West Palaearctic, 2--Nearctic, 3--East Palaearctic-Oriental, 4--West North America, 5--Australia, 6--Neotropical, 7--Sub-Saharan Africa, 8--Palaearctic, and 9--Middle East. Our main conclusion is that there are still some limitations in applying biogeographical classifications proposed mostly on the basis of vertebrate distribution to other taxonomic groups, such as the Tipulidae. While there is a general congruence of the broad-scale areas of endemism of tipulids with previously proposed regionalization schemes, for some areas, the sharpness of boundaries between traditional regions is not so acute, due to a great level of overlap of part of its biotic elements.

Agomelatine treatment of major depressive disorder in Parkinson's disease: a case series.

Major Depressive Disorder (MDD) is among the most frequent comorbidities occurring in the course of Parkinson's disease (PD), and therefore, most PD patients receive antidepressant drugs. Agomelatine is a recently introduced antidepressant drug acting as an MT1/MT2 melatonergic receptor agonist and 5HT2C/5HT2B serotonergic antagonist. The aim of this case series was to evaluate the role of agomelatine in the treatment of MDD associated with PD.

Safety and efficacy of combined clozapine-azathioprine treatment in a case of resistant schizophrenia associated with Behçet's disease: a 2-year follow-up.

Behçet's disease (BD) is a recurrent inflammatory disorder involving multisystems of the body. Neuropsychiatric symptoms, like psychosis and depression, often occur in BD, but the safety and efficacy of combined clozapine-azathioprine treatment have never been assessed. We here report on a 37-year-old man with BD and treatment-resistant schizophrenia who obtained an improvement following the introduction of clozapine in addition to azathioprine, without developing agranulocytosis or other severe adverse side effects during a 2-year follow-up.