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.
Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization ...(WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an
-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
It is well known that alexithymic individuals may show significantly higher levels of anxiety, depression, and psychological suffering than non-alexithymics. There is an increasing evidence that ...alexithymia may be considered a risk factor for suicide, even simply increasing the risk of development of depressive symptoms or
. Therefore, the purpose of this narrative mini-review was to elucidate a possible relationship between alexithymia and suicide risk. The majority of reviewed studies pointed out a relationship between alexithymia and an increased suicide risk. In several studies, this relationship was mediated by depressive symptoms. In conclusion, the importance of alexithymia screening in everyday clinical practice and the evaluation of clinical correlates of alexithymic traits should be integral parts of all disease management programs and, especially, of suicide prevention plans and interventions. However, limitations of studies are discussed and must be considered.
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.
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 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.
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.
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.
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).
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).
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has ...been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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