The Impact of COVID-19 Lockdowns in a Sample of Outpatients in a Mental Health Department of a Metropolitan Hospital in Milan.

Background and Objectives: Italy was the first country in Europe to face the coronavirus 2019 (COVID-19) pandemic and its consequences, which led to two phases of severe restrictions for its population. This study aims to estimate the connections between the trauma of the COVID-19 emergency and the clinical features of a sample of outpatients in a Milan Community Mental Health setting, comparing the first (April 2020) and second lockdowns (November 2020). Materials and Methods: The sample included 116 consecutive outpatients recruited in April 2020 and 116 in November 2020. The subjects were evaluated with Clinical Global Impression Severity (CGI-S), Brief Psychiatric Rating Scale (BPRS-18), and Impact of Event Scale-Revised (IES-R). Results: The IES-R identified 47.4% participants in April and 50% in November with clinical scores over the cut-off. The network analysis of BPRS-18 and IES-R depicted the connection among different symptoms; in April, Unusual Thought Content, Anxiety, and Somatic Concern represented the most central items, and the strongest connections were found between Uncooperativeness and Hostility, Blunted Affect and Emotional Withdrawal, and IES-Intrusion and IES-Arousal. In the November group, the most central items were represented by Conceptual Disorganization and Emotional Withdrawal, whereas the strongest connections were found between IES-Arousal and IES-Intrusion, Excitement and Grandiosity, and Unusual Thought Content and Conceptual Disorganization. Conclusions: Our findings show continued high distress levels and increased psychological burdens during the second phase of restrictions; this could be described as "pandemic fatigue", a general psychological weariness due to pandemic-related restrictions, as well as a lack of motivation to comply with them. As mental health professionals, our mission during these difficult times has been to keep community psychiatry services accessible, with particular regard to vulnerable and marginalized populations.

Correlation between pharmacokinetics and pharmacogenetics of Selective Serotonin Reuptake Inhibitors and Selective Serotonin and Noradrenaline Reuptake Inhibitors and maternal and neonatal outcomes: Results from a naturalistic study in patients with affective disorders.

OBJECTIVE: Some studies have linked the use of selective serotonin reuptake inhibitors and selective serotonin and noradrenaline reuptake inhibitors (SSRIs/SNRIs) to the risk of perinatal complications. This study explored the relationship between pharmacokinetics and pharmacogenetics, SSRIs/SNRIs tolerability and effectiveness and maternal and newborn outcomes. METHODS: Fifty-five pregnant women with Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnoses of affective disorders, treated with SSRIs/SNRIs, were recruited and, during the third trimester, their blood samples were collected for pharmacokinetic and pharmacogenetic analyses. Plasma levels and metabolic phenotypes were then related to different obstetrical and maternal outcomes. RESULTS: The pharmacokinetic data were more stable for Sertraline, Citalopram, and Escitalopram compared to other molecules (p = 0.009). The occurrence of postnatal adaptation syndrome onset was associated with higher plasma levels for Sertraline (median at delivery: 16.7 vs. 10.5 ng/ml), but not for fluoxetine and venlafaxine. Finally, the subgroup within range plasma concentrations had less blood loss than the below range subgroup (p = 0.030). CONCLUSIONS: Plasma levels of Sertraline, Citalopram and Escitalopram were more frequently in range in late pregnancy when compared to other drugs. Drug plasma concentrations do not strictly correlate with worse perinatal outcomes, but with possible differences between the different drugs.

Managing Problematic Usage of the Internet and Related Disorders in an Era of Diagnostic Transition: An Updated Review.

INTRODUCTION: Problematic Usage of the Internet (PUI) refers to a broad and likely heterogeneous group of Internet-related conditions associated with behavioural disturbances and functional impairment. METHODS: Within PUI several conditions have been reported, including Gaming Disorder, Shopping Addiction, Cyberchondria, Gambling Disorder, Cyberpornography Addiction and Cyberbullying. While increasing reports in the field try to define the epidemiologic and clinical boundaries of these conditions, the rapid and continuous evolution of Internet related behaviours as well as their problematic/pathological expressions are often difficult to diagnose, assess, approach with treatment interventions and follow-up. RESULTS: In addition, some of the PUI-related conditions show characteristics of addiction to the Internet as a preferential tool to engage in specific behaviours, while some others exclusively manifest on the Internet, making it necessary to find distinct assessment and treatment pathways. CONCLUSION: The inclusion of Internet Gaming Disorder in Section III by the DSM-5 and the recognition of Gaming Disorder by the ICD-11 opened the way for a systematic clinical investigation of this and other PUI-related conditions, particularly in terms of preventive and therapeutic strategies. The present article is aimed at offering an updated clinical overview on the main expressions of PUI, focussing on the latest acquisitions in this evolving field.

Aripiprazole causing false positive urine amphetamine drug screen in an adult patient with bipolar disorder.

There has been only a few reports regarding aripiprazole causing false positive urine amphetamine drug screens, exclusively on children accidently ingesting aripiprazole. Herein, we present the first reported case of a 40 year old woman affected by Bipolar I Disorder, treated with aripirazole at therapeutic oral dose ranging from 15 mg/day to 30 mg/day, in the context of a depressive episode with mixed and psychotic features, showing a false positive urine amphetamine drug screen. We document the relationship between aripiprazole-dose, plasma concentration and amphetamines values in toxicologic urine examinations over time. Awareness of potential false positive urine amphetamine drug screens during aripiprazole treatment can condition therapeutic choices and prevent legal implications.

Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology.

OBJECTIVE: Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants' pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment. METHODS: In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants' blood concentrations and psychometric assessments were collected at five time points. Antidepressants' cord blood concentrations were assessed at birth. RESULTS: Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants' concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6. CONCLUSIONS: Pregnancy modulates cytochrome activity and drugs' pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.

Treatment-related transient splenial lesion of the Corpus Callosum in patients with neuropsychiatric disorders: a literature overview with a case report.

Introduction: Transient-localized lesions of the splenium of the corpus callosum (SCC) have been described in various clinical conditions, some of them being attributed to the withdrawal of psychotropic drugs. The pathophysiology of the lesion reflects cytotoxic edema and reversible demyelination.Areas covered: The present article aimed at reviewing cases of transient SCC lesion exclusively related to changes in pharmacotherapy. It also reports the original case of a patient receiving a complex psychopharmacological therapy who developed a transient SCC lesion investigated by magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and pharmacogenetic profiling.Expert opinion: To date, only one review on the subject has been published, analyzing 22 cases of transient SCC lesion arising in epileptic patients on antiepileptic therapy. It hypothesized that the nature of the lesion is a cytotoxic edema and the cases described in the subsequent 14 years seem to support this hypothesis. The authors reported the case of an Italian-Egyptian patient who developed a transient SCC lesion after the rapid withdrawal of Carbamazepine and Lurasidone. The lesion completely disappeared from the MRI performed after 1 month. Patient's ethnic group and its pharmacogenetic profile were considered as possible causes of altered drug metabolism and, likely, of the SCC lesion.

Anxiety disorders anticipate the diagnosis of bipolar disorder in comorbid patients: Findings from an Italian tertiary clinic.

BACKGROUND: Studies indicate bipolar disorder (BD) syndromal symptoms are commonly preceded by sub-syndromal BD symptoms, dysregulated sleep, irritability, and anxiety. We aimed to evaluate prevalence and clinical correlates of anxiety disorders (ADs) at BD onset in outpatients with versus without at least one AD at BD onset. METHODS: 246 bipolar spectrum outpatients, according to the text revision of the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM- IV-TR), attending Sacco University Hospital in Milan, were recruited and their onset and clinical features assessed retrospectively. Patients were stratified into those with versus without an AD at BD onset (w/A and wo/A), according to a semi-structured clinical interview to provide diagnoses according to (DSM- IV-TR). RESULTS: 29% of patients reported being w/A, among whom Panic Disorder (PD, in 55.6%) was the most frequent AD, and first AD occurred approximately 4 years before BD diagnosis. Patients w/A versus wo/A had higher (p < 0.05) rates of BDII and first mood episode being depression versus elevation (mania/hypomania), and lifetime rates of separation anxiety disorder, substance poly-abuse and benzodiazepine abuse. In contrast, patients wo/A had higher lifetime rates of alcohol and illicit drug use. CONCLUSION: In this naturalistic sample, ADs, in particular PD, preceded BD in almost 1/3 of BD outpatients, and had distinctive clinical correlates. Further investigation into relationships between BD and AD at onset may enhance early BD diagnosis and treatment.

Postpartum Bleeding in Pregnant Women Receiving SSRIs/SNRIs: New Insights From a Descriptive Observational Study and an Analysis of Data from the FAERS Database.

PURPOSE: To date, the available data on the relationship between the use of selective serotonin reuptake inhibitors (SSRIs) or the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine and postpartum hemorrhage (PPH) are conflicting and have not been extensively investigated, especially in terms of plasma drug concentrations. We performed data mining of antidepressant-induced PPH reported to the US Food and Drug Administration's Adverse Event Reporting System database, to assess the strength of the potential association between antidepressant pharmacotherapy and PPH in pregnant women. Concurrently, we carried out a descriptive observational population (pregnant women) analysis of the correlation between the plasma concentrations of SSRIs/SNRIs used during pregnancy and the extent of bleeding at delivery. METHODS: A disproportionality analysis of individual case study reports of PPH associated with SSRIs or venlafaxine in pregnant women was performed. Reporting odds ratio was used as a measure of disproportionality analysis. Pregnant women treated with an SSRI or SNRI (venlafaxine) for depressive or anxiety disorder and who consented to plasma drug concentration monitoring at the time of delivery were recruited. Plasma drug concentration assay was performed according to validated LC-MS/MS. Based on plasma drug concentrations, patients were classified into 1 of 2 groups, in therapeutic range or below therapeutic range for the drug administered, in accordance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie guideline, and correlations with blood loss were identified, with PPH defined as a blood loss of >500 mL. FINDINGS: Only 43 Individual Case Safety Reports (ICSRs) reported at least one SSRIs or venlafaxine as suspect drug in 14 years (database analyses). Forty-three women were enrolled in the study population (observational study). In 24 patients (55.8%) the plasma drug concentration was below the therapeutic threshold. Unexpectedly, the mean blood loss in the below-range group was significantly higher than that in the in-range group. PPH occurred in 30% of women: in 9.3% and in 20.7% of patients in the in-range and below-range groups, respectively. IMPLICATIONS: Although preliminary, these data indicate a rather good tolerability profile of SSRIs/SNRIs regarding postpartum bleeding. Moreover, they suggest that keeping the plasma levels of SSRIs/SNRIs low as a precautionary measure does not reduce postpartum bleeding, which was higher in the below-range group. The findings from this study suggest that the use of therapeutic drug monitoring in pregnancy, a period in which multiple variables affect drug metabolism, may allow for better treatment customization, with subsequent advantages in terms of tolerability and efficacy of treatment.