The mediating role of alexithymia in the relationship between affective temperament and craving: Cross-sectional study conducted in a sample of bipolar and alcohol use disorder patients.

BACKGROUND: Bipolar disorder (BD) and alcohol use disorder (AUD) commonly co-occur and their interplay is influenced by several factors. Alexithymia is connected to BD and AUD; affective temperaments serve as risk factors for both; craving contributes to the development and maintenance of AUD. The present study tested whether alexithymia play a mediating role in the relationship between affective temperaments and craving in alcoholic bipolar patients. METHODS: 151 alcoholic bipolar patients (38 % females, mean age: 45.69 ± 9.04 years) were enrolled. The Mini International Neuropsychiatric Interview (MINI), the Brief Psychiatric Rating Scale (BPRS), the Toronto Alexithymia Scale (TAS-20), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego scale (TEMPS-A), and the Typology Craving Questionnaire (CTQ) were administered. Correlations among TAS-20, TEMPS-A, CTQ were conducted. Regression analyses were applied to verify the mediating hypothesis. RESULTS: Difficulty in identifying feelings mediated the association between anxious temperament and craving (Indirect effect: 0.42, BCaCI: 0.22-0.69), cyclothymic temperament and craving (Indirect effect: 0.55, BCaCI: 0.30-0.87), irritable temperament and craving (Indirect effect: 0.45, BCaCI: 0.19-0.80). TAS-20 difficulty in communicating feelings to others mediated the association between anxious temperament and craving (Indirect effect: 0.20, BCaCI: 0.06-0.41). LIMITATIONS: The sample size did not allow subgroup analyses. Data were collected cross-sectionally and in a single center. We did not investigate whether BD or AUD occurred first, although it might influence the mediation role of alexithymia. CONCLUSION: Among alcoholic bipolar patients, assessing and targeting alexithymia may be useful to modulate craving and, in turn improve, the general mental status of patients.

Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study).

Background: Treatment-resistant Depression (TRD) represents a widespread disorder with significant direct and indirect healthcare costs. esketamine, the S-enantiomer of ketamine, has been recently approved for TRD, but real-world studies are needed to prove its efficacy in naturalistic settings. Objectives: Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services. Methods: REAL-ESK study is an observational, retrospective and multicentric study comprising a total of 116 TRD patients treated with esketamine nasal spray. Anamnestic data and psychometric assessment (MADRS, HAMD-21, HAM-A) were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups. Results: A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. A dramatic increase in clinical response (64.2 %) and remission rates (40.6 %) was detected at T2 compared to T1. No unexpected safety concerns were observed, side effects rates were comparable to those reported in RCTs. No differences in efficacy have been found among patients with and without psychiatric comorbidities. Limitations: The open design of the study and the absence of a placebo or active comparator group are limitations. The study lacks an inter-rater reliability evaluation of the assessments among the different centres. Side effects evaluation did not involve any specific scale. Conclusions: Our findings support the safety and tolerability of esketamine in a real-world TRD sample. The later response and the non-inferiority in effectiveness in patients with comorbidities represent novel and interesting findings.

Trazodone Add-on in COVID-19-related Selective Serotonin Reuptake Inhibitor-resistant Post-traumatic Stress Disorder in Healthcare Workers: Two Case Reports.

COVID-19 represents a significant stress factor for all people worldwide due to several factors, including quarantine, lockdowns, fear of contagion, deaths, and other traumatic events. However, the healthcare workers (HCWs) have paid the higher price of this pandemic in terms of fatalities, contagions, and psychological well-being. Studies suggest that this particular population is at increased risk of developing a severe post-traumatic stress disorder (PTSD). The early diagnosis and timely treatment of PTSD in HCWs may restore well-being and significantly impact health services functioning, reducing burnout, days spent far from work, disrupted personal and team empowerment, and worse job performances. In the present article, we reported on two cases of HCWs directly involved in the treatment of COVID-19 patients who showed selective serotonin reuptake inhibitor-resistant PTSD, which was successfully treated with extended-release trazodone TRZ ContramidⓇ add-on.

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.

Oxidative Stress in the Early Stage of Psychosis.

BACKGROUND: In the past few decades, increasing evidence in the literature has appeared describing the role of the antioxidant defense system and redox signaling in the multifactorial pathophysiology of psychosis. It is of interest to clinicians and researchers alike that abnormalities of the antioxidant defense system are associated with alterations of cellular membranes, immune functions and neurotransmission, all of which have some clinical implications. METHODS: This narrative review summarizes the evidence regarding oxidative stress in the early stages of psychosis. We included 136 peer-reviewed articles published from 2007 to 2020 on PubMed EMBASE, The Cochrane Library and Google Scholar. RESULTS: Patients affected by psychotic disorders show a decreased level of non-enzymatic antioxidants, an increased level of lipid peroxides, nitric oxides, and a homeostatic imbalance of purine catabolism. In particular, a significantly reduced antioxidant defense has been described in the early onset first episode of psychosis, including reduced levels of glutathione. Also, it has been shown that a decreased basal low-antioxidant capacity correlates with cognitive deficits and negative symptoms, mostly related to glutamate-receptor hypofunction. In addition, atypical antipsychotic drugs seem to show significant antioxidant activity. These factors are critical in order to treat cases of first-onset psychosis effectively. CONCLUSION: This systematic review indicates the importance that must be given to anti-oxidant defense systems.

Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment.

The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut-brain-microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.

Suicide in Healthcare Workers: Determinants, Challenges, and the Impact of COVID-19.

The Coronavirus disease-19 (COVID-19), which first appeared in Wuhan, China, and was later declared a pandemic, has caused significant morbidity and mortality worldwide. Numerous efforts have been made worldwide to understand the disease's physical manifestation. However, less emphasis has been placed on the pandemic's mental health challenges for healthcare workers (HCWs) who played a critical role in fighting the disease. Existing literature shows the detrimental psychological impact and increased incidence of depression and anxiety among HCWs. It is expected that the mental health crisis will become a serious issue affecting HCWs, with long-term negative consequences following COVID. Physicians and nurses already represent the highest risk groups of suicide among the general population, and suicide can be regarded as an occupational hazard in the healthcare industry. Increased workload, burnout and fatigue, multifaceted challenges women HCWs, and increased substance abuse are contributing factors to suicide ideation. In this article, we identify the risk factors of suicide among HCWs, discuss mental health challenges exacerbated by the pandemic and its impact on suicide ideation.

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.

Psychopathological Burden and Quality of Life in Substance Users During the COVID-19 Lockdown Period in Italy.

BACKGROUND: Following the development of the COVID-19 pandemic, a rigid public health strategy of reduced social contact and shelter-in-place has been adopted by the Italian Government to reduce the spread of the virus. In this paper, we aim at evaluating the impact that the COVID-19 pandemic, and the relative containment measures, have had on a real-life sample of patients suffering from substance use disorders (SUDs) and/or behavioral addictions. METHODS: An anonymous questionnaire was filled out by 153 addicted patients, both outpatients and residential inpatients, recruited across Italy and highly representative of the current Italian population suffering from addictions. Psychopathological burden (anxiety and depressive symptomatology, somatization, irritability, and post-traumatic symptoms), quality of life, and craving changes in daily habits were assessed. RESULTS: In our sample, we found moderate rates of depression (22.9%), anxiety (30.1%), irritability (31.6%), and post-traumatic stress (5.4%) symptoms. Psychopathological burden was globally higher among residential patients. Reported levels of craving were generally low. DISCUSSION: This study is the first attempt to collect Italian data regarding the effects of the rigid quarantine period, during the COVID-19 pandemic, on patients suffering from a SUD and/or behavioral addictions. The presence of a moderate psychopathological burden correlated to poor quality of life and low craving scores represented the main outcomes. Long-term studies, with follow-up after the end of the restrictive measures, should be considered to implement our findings.

The 'dead man walking' disorder: an update on Cotard's syndrome.

In 1880, Jules Cotard described a peculiar syndrome after observing the case of a 43-year-old woman, which was characterized by melancholic anxiety, delusions of damnation or possession, a higher propensity to suicide ideation and deliberate self-harm, analgesia, hypochondriac thoughts of non-existence or ruin of several organs, of the whole body, of the soul, of divinity, and the idea of immortality or inability to die. Several expansions and reinterpretations have been made of the so-called Cotard's syndrome, which is often encompassed in different neurological and psychiatric disorders, complicating and worsening their symptomatic frameworks and making more difficult their treatments. However, the nosographic characterization of Cotard's syndrome remains elusive and is not now classified as a separate disorder in both ICD and DSM-5. Here, we try to give an update, as well as a putative systematization, of current views and opinions about this nosological entity in the light of the recent progress in the clinic, psychopathology and psycho-neurobiology.

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.

Understanding the Complex of Suicide in Depression: from Research to Clinics.

OBJECTIVE: Amongst psychiatric disorders, major depressive disorder (MDD) is the most prevalent, by affecting approximately 15-17% of the population and showing a high suicide risk rate equivalent to around 15%. The present comprehensive overview aims at evaluating main research studies in the field of MDD at suicide risk, by proposing as well as a schematic suicide risk stratification and useful flow-chart for planning suicide preventive and therapeutic interventions for clinicians. METHODS: A broad and comprehensive overview has been here conducted by using PubMed/Medline, combining the search strategy of free text terms and exploded MESH headings for the topics of 'Major Depressive Disorder' and 'Suicide' as following: ((suicide [Title/Abstract]) AND (major depressive disorder [Title/Abstract])). All articles published in English through May 31, 2019 were summarized in a comprehensive way. RESULTS: Despite possible pathophysiological factors which may explain the complexity of suicide in MDD, scientific evidence supposed the synergic role of genetics, exogenous and endogenous stressors (i.e., interpersonal, professional, financial, as well as psychiatric disorders), epigenetic, the hypothalamic-pituitary-adrenal stress-response system, the involvement of the monoaminergic neurotransmitter systems, particularly the serotonergic ones, the lipid profile, neuro-immunological biomarkers, the Brain-derived neurotrophic factor and other neuromodulators. CONCLUSION: The present overview reported that suicide is a highly complex and multifaceted phenomenon in which a large plethora of mechanisms could be variable implicated, particularly amongst MDD subjects. Beyond these consideration, modern psychiatry needs a better interpretation of suicide risk with a more careful assessment of suicide risk stratification and planning of clinical and treatment interventions.

An Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine.

BACKGROUND: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. OBJECTIVE: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. METHODS: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. RESULTS: Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. CONCLUSION: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.

Rapid improvement of obsessive-compulsive disorder associated with schizophrenia with cariprazine add-on in a subject under paliperidone long-acting injection: a case report.

Obsessive-compulsive disorder is often associated with schizophrenia and may represent a significant challenge in the treatment as this comorbidity may not respond properly to antipsychotic medication and usually require a pharmacological and psychotherapeutic add-on. In the present case report, we present the case of a 26-year-old male blue-collar subject who developed obsessive-compulsive disorder after a year of complete remission of schizophrenia symptoms under paliperidone long-acting injection that rapidly resolved after low-dosage cariprazine add-on. No adverse effects were reported due to cariprazine- paliperidone long-acting injection combination.

Alexithymia as a possible specifier of adverse outcomes: Clinical correlates in euthymic unipolar individuals.

BACKGROUND: Alexithymia is a disabling condition frequently linked to major depressive disorder (MDD) and able to enhance symptoms severity and suicide risk. This study aimed to clarify whether patients with and without alexithymia may differ concerning illness presentation and clinical course, which is a major gap in the scientific literature. METHODS: The present sample included 381 euthymic outpatients with MDD recruited at the Department of Neuroscience (DINOGMI), University of Genoa. The Toronto Alexithymia Scale (TAS-20) and additional rating scales (Clinical Global Impression (CGI), Hamilton Anxiety Rating Scale (HAM-A), Intent Score Scale (ISS) were administered to all participants. RESULTS: Alexithymic patients were more likely to have lower educational level (11.6 ±â€¯3.2 vs. 12.4 ±â€¯3.4, p ≤ .05), have used previous psychiatric drugs (85.7% vs. 72.8%, p =.001), use current antidepressants (84.7% vs. 69.4%, p = <.001), and have higher cardiological comorbid disorders (10.7% vs. 5.0%, p = ≤.05). After multivariate analyses, alexithymia was associated with lower educational level (OR=0.928, p = .05), and higher current antidepressants use (OR 2.302, p = .01); difficulties in identifying feelings were associated with lower educational level (p = ≤.005), higher psychiatric comorbidity (p = ≤.001), and previous psychiatric medications (p = .01). Furthermore, having a lower educational level remained the only factor associated with both difficulties in communicating feelings (p = ≤.001) and thoughts oriented to external context (p = ≤.005). LIMITATIONS: The study is limited by the small sample size and its cross-sectional nature. CONCLUSIONS: Alexithymia appears a useful specifier of adverse outcomes, associated with distinct socio-demographic and clinical characteristics. Its identification would allow to provide a more personalized care.

Alexithymia, resilience, somatic sensations and their relationships with suicide ideation in drug naïve patients with first-episode major depression: An exploratory study in the "real world" everyday clinical practice.

AIM: The present study is aimed at revaluating alexithymia, somatic sensations, resilience and their relationships with suicide ideation in drug naïve adult outpatients suffering from first episode major depression (MD). METHODS: Data of 103 adult outpatients (49 men, 56 women) with a diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) diagnosis of MD were analysed. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) and resilience with the 25 items Connor-Davidson Resilience Scale (CD-RISC) whereas depression was evaluated using the 17-item Hamilton Depression Rating Scale, somatic sensations with the Body Sensations Questionnaire and suicide ideation with Scale of Suicide Ideation (SSI). RESULTS: Gender comparisons between all demographic and clinical variables showed no significant differences in all variables. Subjects who were found positive for alexithymia showed higher scores on all clinical variables controlling for age, gender and duration of the current episode. In a linear regression model, lower scores on CD-RISC and Difficulty in Identifying Feelings dimension of TAS-20 were significantly predictive of higher scores on SSI. CONCLUSIONS: Alexithymia and low resilience were significant predictors of increased suicide ideation in a first MD episode. However, study limitations must be considered and future research needs are being discussed.

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.

Novel Pathways in the Treatment of Major Depression: Focus on the Glutamatergic System.

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further "neurobiological targeted" approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.