Foreign Nationality, Family Psychiatry History and Pregestational Neoplastic Disease as Predictors of Perinatal Depression in a Cohort of Healthy Pregnant and Puerperal Women during the COVID-19 Pandemic.

Background: Perinatal depression (PND) represents one of the most common mental disorders in the pregnancy and/or postpartum period, with a 5-25% prevalence rate. Our aim was to investigate predictors associated with PND in a cohort of pregnant and puerperal women based in an Italian setting during the COVID-19 pandemic. Methods: We retrospectively recruited 199 (55 pregnant and 144 puerperal) women, afferent to our Perinatal Mental Outpatient Service of Ancona (Italy). Participants were administered an ad hoc case-report form, Whooley Questions (WQ), the General Health Questionnaire-12 (GHQ-12), the Stress Holmes-Rahe scale (HR) and the Edinburgh Postnatal Depression Scale (EPDS). Results: Around 10% of the sample had a confirmed PND. Being a foreigner woman (RR = 3.8), having a positive psychiatric family history (RR = 5.3), a pre-pregnancy medical comorbidity (RR = 1.85) and a comorbid medical illness occurring during the pregnancy (RR = 2) were much likely associated with PND. Multiple linear regression analysis demonstrated that GHQ, medium- and high-risk at the HR, foreign nationality, positive family psychiatric history, and neoplastic disease before conception significantly predicted EPDS [F(1, 197) = 10.086, R2 = 0.324, p < 0.001]. Limitations: The sample size, poor heterogeneity in terms of socio-demographic, clinical and gynecological-obstetric characteristics, the cross-sectional design of the study. Conclusions: Our study showed a set of predictors associated with a higher risk for the PND onset, including gestational and pregestational medical disease. Our findings outline the need to screen all fertile women, particularly in gynecological and medical settings, in order to identify at-risk women for PND and promptly suggest a psychiatric consultation.

Craving and addictive potential of esketamine as side effects?

INTRODUCTION: Esketamine was approved for adults with treatment-resistant depression (TRD) in conjunction with an oral antidepressant, and for treating depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. However, evidence of great efficacy and safety of esketamine is accompanied by a widespread concern regarding its addictive potential. AREAS COVERED: A comprehensive review on the craving and addictive potential of ketamine and esketamine was carried out. In addition, a clinical case of a 34-year-old TRD woman treated with esketamine who experienced drug-seeking behaviors and craving symptomatology was described and critically discussed, with a particular focus on treatment strategies to manage craving in the short- and long term. EXPERT OPINION: Esketamine showed great efficacy and safety in treating TRD and MDD with acute suicidal ideation or behavior. Our clinical experience demonstrated the presence of an additive potential, which has been favorably managed with slow esketamine de-titration and combination with bupropion. However, literature so far published is scant and shows contradictory findings. Therefore, it is crucial to promptly detect and manage craving symptomatology in esketamine-treated TRD patients. In our experience, the use of bupropion to counteract craving and addictive symptoms was proven to be effective and safe.

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

Up-to-date expert opinion on the safety of recently developed antipsychotics.

Introduction There are several new and emerging antipsychotic medication strategies recently marketed or under clinical development for the treatment of several mental disorders. There is the need to provide an up-to-date overview on the safety of this new generation of antipsychotic medications, which includes also the third-generation antipsychotics (TGA). Areas covered The authors aimed at providing a synthesis of the most current evidence about the safety profile of the recently developed and/or marketed antipsychotics. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library from inception until March 2020, combining free terms and MESH headings for the topics of TGA and recently developed and/or marketed antipsychotics as following: ((safety OR adverse events OR side effects) AND ((brexpiprazole OR cariprazine OR inhaled loxapine OR lumateperone (ITI-007) OR lurasidone OR pimavanserin OR roluperidone (MIN-101) OR transdermal patch asenapine)). Expert opinion Overall, newer antipsychotics display a good safety profile, with a well-demonstrated lower metabolic liability compared to second-generation antipsychotics. Furthermore, TGA appear to specifically target negative symptomatology and improving cognitive domains. Abbreviations Aps=Antipsychotic Drugs; AEs = Adverse Effects; EPS = Extrapyramidal Symptoms; NMS = Neuroleptic malignant syndrome; D = Dopamine; Ki = Inhibitory Constant; 5-HT = Serotonin; ECG = Electrocardiogram; H = Histamine; M = Muscarinic; BMI = Body Mass Index.

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.

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.

Is there a Teratogenicity Risk Associated with Cannabis and Synthetic Cannabimimetics' ('Spice') Intake?

BACKGROUND: Substance use, including cannabis, has been documented amongst women both in the pre-conception period and during pregnancy, particularly during the 1st trimester, which is clearly the most critical period in the organogenesis. The recent emergence on the drug market of synthetic cannabimimetics/SC ('spice') may represent a new challenge for clinicians. OBJECTIVE: A literature overview on the teratogenicity profile of both cannabis and synthetic cannabimimetics was here carried out. METHOD: The PubMed database was searched in order to collect all relevant cases and data regarding the possible evidence of teratogenicity issues associated with cannabis and SC intake. RESULTS: The use of cannabis in pregnant women has been associated with a plethora of both obstetrical/ gestational complications and neurobehavioral/neurological effects on newborns. Conversely, only few and conflicting data are related to SC misuse issues. CONCLUSION: Although cannabis use may be considered a risk factor for the occurrence of pregnancyrelated morbidity issues, many studies relied on self-reports and showed inconsistent results when controlling for potential confounders, including tobacco use. Given the role of the endocannabinoid system in both pregnancy and delivery, SC potency at interacting with the endocannabinoid system may be a reason of concern. Clinicians should carefully assess each woman planning a pregnancy, or who is pregnant already, and who is at risk of persisting in her current cannabis and/or SC intake. A nonjudgmental approach, aiming at collecting both a history of drug/alcohol use and at providing information regarding the risks associated with cannabis/SC intake during pregnancy is here advised.

Effect of agomelatine treatment on C-reactive protein levels in patients with major depressive disorder: an exploratory study in "real-world," everyday clinical practice.

OBJECTIVE: Agomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients. METHODS: 30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in "real-world," everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment. RESULTS: Agomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose. CONCLUSIONS: Agomelatine's antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder.

OBJECTIVE: To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). DATA SOURCES: A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR depression)). Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized controlled trials and open trials involving humans were here included and analyzed. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. DATA SYNTHESIS: SAMe is an important physiologic compound, playing a central role as precursor molecule in several biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. CONCLUSION: Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy of this drug.