New psychoactive substances (NPS) and serotonin syndrome onset: A systematic review.

The use of several new psychoactive substances (NPS) has become very popular and is posing global health risks. Chemically and pharmacologically diverse molecules are constantly emerging and are presenting with a wide range of clinical implications. Serotonin toxicity, and specifically Serotonin Syndrome (SS), might develop as a result of an over-activation of the serotoninergic system caused by several mechanisms resulting in a classic triad of altered mental status, neuromuscular effects, and autonomic hyperactivity. In the present systematic review, we have investigated and summarized the available evidence related to the association between SS and NPS intake. Three retrospective studies, two case series and five case reports were included in this systematic review; several NPS were found to be implicated in SS occurrence These include psychedelic phenethylamines, e.g. 2, 5-dimethoxy-4-iodophenethylamine (2C-I); 2-(4-Iodo-2,5-dimethoxyphenyl)- N-I[(2-methyoxyphenyl)methyl]ethanamine (25I-NBOMe); and 5-(2-aminopropyl)indole (5-IT); and synthetic cathinones, e.g. mephedrone; 3,4-methylenedioxypyrovalerone (MDPV); methylone; butylone; NRG3; alpha-methyltryptamine (AMT); methoxphenidine (MXP); and the antidepressant bupropion. Bupropion was here misused at high dosages and/or in combination with other licit/illicit serotonergic drugs. Whilst most substances were ingested orally, nasal insufflation (with both 5-IT and 2C-I) and sublingual administration of blotter paper (with 25I-NBOMe) were reported as well. Interestingly, the psychiatric history was negative for most subjects, apart from two cases. Clinicians should be aware of NPS potential risks and the severe consequences of their recreational use, including SS. Also, due to their undetectability in routine and common drug screenings, the diagnostic challenges posed by NPS should not be underestimated during the treatment of such patients.

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 D 3 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.

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-19patients who showed selective serotonin reuptake inhibitor-resistant PTSD, which was successfully treated with extended-release trazodone TRZ ContramidⓇ add-on.

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.

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.