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The debate around optimal target dose for first-line antidepressants (ADs) is still ongoing. Along this line, therapeutic drug monitoring (TDM) represents one of the most promising tools to improve clinical outcome. Nevertheless, a few data exist regarding the concentration-effect relationship of first-line ADs which limits TDM implementation in routine clinical practice. We conducted the first patient-level concentration-response mega-analysis including data acquired by us previously and explored the concentration dependency of first-line AD (206 subjects). Further, new data on mirtazapine are reported (18 subjects). Hamilton Depression Rating Scale-21 administered at baseline, at month 1 and month 3 was used as the measure of efficacy to assess antidepressant response (AR). When pooling all four first-line ADs together, normalized plasma levels and AR significantly fit a bell-shaped quadratic function with a progressive increase of AR up to around the upper normalized limit of the therapeutic reference range with a decrease of AR at higher serum levels. Our results complement the available evidence on the issue and the recent insights gained from dose-response studies. A concentration-dependent clinical efficacy, such as previously demonstrated for tricyclic compounds, also emerge for first-line ADs. Our study supports a role for TDM as a tool to optimize AD treatment to obtain maximum benefit.

Contains fulltext : 238693.pdf (Publisher’s version ) (Open Access) Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient.Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

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.Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services.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.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.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.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.

Objective Therapeutic drug monitoring helps clinicians in choosing the right drug and adjust its dose in specific patients. To this end, we aimed to assess time patterns of risperidone and its metabolite, 9-hydroxyrisperidone, in children and adolescents with oppositional defiant and/or conduct disorder. Methods We measured plasma concentrations of risperidone and 9-hydroxyrisperidone, their sum (active moiety, AM) and ratio, as well as plasma concentrations corrected for daily dose (C/D), from 140 children/adolescents with the above-mentioned disorders. We used Student's t test to compare females versus males, patients under versus over 16-year-old, patients with lower versus higher than the median body weight, and patients with lower versus higher than the median body mass index (BMI). Two mixed-effects logistic regression models were fitted for risperidone/9- hydroxyrisperidone ratio and AM, respectively, by considering risperidone daily dose and patients' demographic characteristics. Results Females had higher 9-hydroxyrisperidone and AM plasma concentrations than males (p = 0.004 and p = 0.034). Younger patients had lower risperidone plasma concentration and risperidone/9-hydroxyrisperidone ratio (p = 0.02 and p = 0.021), but higher C/D 9-hydroxyrisperidone and AM than older patients (p = 0.013 and p = 0.043). Lower-weight patients had lower plasma risperidone and risperidone/9-hydroxyrisperidone ratio (p = 0.014 and p = 0.019), but higher C/D 9-hydroxyrisperidone concentration than heavier patients (p = 0.03). All these results could be accounted for by daily dose. Patients with lower and higher BMI did not differ significantly. Regression analyses showed that only risperidone daily dose predicted risperidone/9-hydroxyrisperidone ratio, whereas risperidone daily dose, sex, and age predicted AM. Conclusion Clinicians prescribing risperidone need to consider sex, age, and weight, but not BMI when adjusting daily doses.

Attention Deficit and Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that often persists into adult-hood. The Italian situation regarding the clinical management of childhood ADHD shows some criticalities, despite the high preva-lence rate: diagnostic assessments are often inaccurate, protocols for transition from childcare services are almost non-existent and theItalian National Registry for ADHD in childhood was drawn up only in 2007, hence the first specialized services were created laterthan the rest of Europe. On the basis of these issues, we investigated the Italian situation with regard to disorders in adulthood, com-paring the different European operational models, assuming that these critical issues are reflected in the clinical management of thedisorder in adulthood. In fact, unlike other European countries, there are no official guidelines governing the clinical management ofthe disorder in adulthood and evidence-based pharmacotherapies, available in most European countries, are off-label or not allowedin Italy. The aim of the study is to evaluate the current state of knowledge and working method in relation to adult ADHD in the Ital-ian background and to identify the main evaluation and treatment pathways in Italian Mental Health Services. The study is also an at-tempt to clarify which services are operational on the Italian territory, with the aim of improving the quality of interventions for theclinical population. Three hundred thirty-eight services have been identified in all Italian Regions and Autonomous Provinces, includ-ing Mental Health Centres (CSM), Pathological Addition Services (SERD), Psychiatric Diagnosis and Treatment Services (SPDC). Anad-hoc survey with closed-ended questions was administered by telephone to each selected centre and the results were compared withthe European literature.

Attention Deficit and Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. The Italian situation regarding the clinical management of childhood ADHD shows some criticalities, despite the high prevalence rate: diagnostic assessments are often inaccurate, protocols for transition from childcare services are almost non-existent and the Italian National Registry for ADHD in childhood was drawn up only in 2007, hence the first specialized services were created later than the rest of Europe. On the basis of these issues, we investigated the Italian situation with regard to disorders in adulthood, comparing the different European operational models, assuming that these critical issues are reflected in the clinical management of the disorder in adulthood. In fact, unlike other European countries, there are no official guidelines governing the clinical management of the disorder in adulthood and evidence-based pharmacotherapies, available in most European countries, are off-label or not allowed in Italy. The aim of the study is to evaluate the current state of knowledge and working method in relation to adult ADHD in the Italian background and to identify the main evaluation and treatment pathways in Italian Mental Health Services. The study is also an attempt to clarify which services are operational on the Italian territory, with the aim of improving the quality of interventions for the clinical population. Three hundred thirty-eight services have been identified in all Italian Regions and Autonomous Provinces, including Mental Health Centres (CSM), Pathological Addition Services (SERD), Psychiatric Diagnosis and Treatment Services (SPDC). An ad-hoc survey with closed-ended questions was administered by telephone to each selected centre and the results were compared with the European literature.

Knowledge about the impact of body composition features on pharmacokinetics of newer long-acting injectable antipsychotics is limited.We analyzed steady-state plasma concentrations of paliperidone in different body mass index (BMI), age, sex, and smoking status patient subgroups treated with once-monthly paliperidone palmitate (PP1M). Paliperidone plasma concentrations and dose-adjusted-plasma concentrations (C/D) from a therapeutic drug monitoring (TDM) database of PP1M-treated patients were compared among normal BMI, overweight, and obese patients as well as between females vs. males, elderly vs. non-elderly, and smokers vs. non-smokers using non-parametric tests.In a total of 183 PP1M-treated patients, we found highly variable paliperidone plasma concentrations between individuals but no significant effect of PP1M dose or dosing intervals (Our findings suggest that age, sex, smoking, or body weight may not substantially affect pharmacokinetic indices of PP1M. The high interindividual variation of plasma concentrations implies that TDM may be helpful to enhance PP1M efficacy and tolerability.

The objective of this study was to investigate associations between pharmacokinetic correlates and once-monthly paliperidone palmitate (PP1M)-related adverse drug reactions (ADRs). Plasma concentrations and dose-adjusted plasma concentrations (‘concentration-by-dose’ [C/D]) of paliperidone from a naturalistic therapeutic drug monitoring database of PP1M-treated patients were compared between patients with ADRs, classified according to the Udvalg for Kliniske Undersogelser side-effect rating scales categories, and patients without ADRs. Analyses included non-parametric tests and a logistic regression model with a significance level set at 0.05. In 172 patients, we found no differences in sex, age, smoking, body mass index, PP1M dose, paliperidone plasma concentrations, and C/D values (p > 0.05) between 44 patients with and 128 patients without PP1M-related ADRs. We did not detect differences when specifying for different types of ADRs (p > 0.05). Injection intervals were shorter in patients with vs patients without ADRs (p = 0.03). The logistic regression did not report effects for sex, plasma concentrations, or C/D values (p > 0.05). Post hoc analyses in male patients receiving PP1M every 28 weeks reported higher paliperidone concentrations and C/D values in patients with vs without ADRs (p = 0.049 and p = 0.022). Within the group of male patients, we found an odds ratio of 3.07 for PP1M-associated ADRs in patients with C/D values above 7.7 (ng/mL)/(mg/day). Our findings did not reveal distinct patterns of paliperidone concentrations in patients with PP1M-related ADRs. However, male patients receiving PP1M every 28 days with C/D values higher than 7.7 (ng/mL)/(mg/day) showed a higher risk for ADRs, implying that therapeutic drug monitoring may be useful in assessing the risk of PP1M-related ADRs.

(1) Background: In their efforts to contain the spread of COVID-19, most countries closed schools and kindergartens. To date, little is known about the strategies of working families reconciling work and parenting during repeated lockdown situations. (2) Methods: We performed a quantitative survey of working parents in Italy during a week of ‘hard lockdown’ in February/March 2021. (3) Results: 3725 voluntary adult participants from different households responded. Though officially not allowed, 53.4% of all participants sought help from people outside the nuclear family to bridge the situation, mostly the grandparents (79%, n = 1855). Overall, parental coping strategies included alternating working–childcare-turns with their partner (35%, n = 1316), working early in the morning or during nighttime (23%, n = 850), or leaving the children unattended (25%, n = 929). (4) Conclusions: The closure of schools/kindergartens forcefully shifts the responsibility for childcare onto the nuclear family, where new strategies arose, including health-damaging models of alternating work–childcare-shifts, ‘illegal’ involvement of third parties from outside the nuclear family, as well as neglect of age-related childcare. Our findings underline that working families need additional support strategies during repeated closure of childcare institutions to be able to reduce contact and minimize secondary damage.

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The field of suicide prevention has been enriched by research on the association between spirituality and suicide. Many authors have suggested focusing on the various dimensions of religiosity in order to better understand the association between religion and suicidal risk, but it is unclear whether the relationship between spirituality and suicidality differs between countries with different cultures, life values, and sociohistorical experiences. To explore this, the aim of this multicenter study was to investigate the possible relationship between suicide and spirituality in Italy and Austria. In the two countries, two different groups of subjects participated: psychiatric patients and university students. The patients were evaluated with the Mini International Neuropsychiatric Interview. In addition, the following measures were used: a sociodemographic questionnaire, the Columbia-Suicide Severity Rating Scale-B, the Symptom-Checklist-90-Standard, and the Multidimensional Inventory for Religious/Spiritual Well-Being. Our results confirmed the multifactorial nature of the relation between suicide risk and the various religious/spiritual dimensions, including religious/spiritual well-being and hope immanent. However, regional differences moderated this relationship in both the clinical and nonclinical samples.

Background Major Depressive Disorder (MDD) is associated with a high rate of inadequate treatment response, which is mainly due to the large inter-individual genetic variability in pharmacokinetic and pharmacodynamic targets of antidepressant drugs. Little is still known about the exact association between plasma level of first-line antidepressants and clinical response. This is particularly true for duloxetine, a dual serotonin and norepinephrine reuptake inhibitor recommended as first-line treatment for MDD. The aim of this study was to investigate the association between serum concentration of duloxetine (SCD) and antidepressant response (AR). Methods 66 MDD patients treated with duloxetine 60 mg/day monotherapy were recruited in an outpatient setting and followed for three months. Hamilton Depression Rating Scale - 21 (HAMD-21) was administrated at baseline, at month 1, and at month 3 to assess AR. SCD was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCD and AR. Results SCD showed a high inter-individual variability in our sample, despite the duloxetine fixed oral dosage. We found a strong association between SCD and AR following a bell-shaped function at month 1 and at month 3. Nonetheless, within the recommended SCD range of 30–120 ng/mL a more linear correlation between SCD and AR was observed. Discussion Our results suggest that for duloxetine the association between SCD and AR likely follows a bell-shaped quadratic function with poor AR at subtherapeutic SCD and progressive decrease of AR at higher SCD. The maximum antidepressant efficacy seems to require SCD values next to the highest recommended SCD (30–120 ng/mL), probably because of the optimal saturation of both serotonin and norepinephrine transporters. Thus, taking into account the observed high interindividual variability of SCD, our findings suggest that for MDD patients treated with duloxetine, SCD could be a useful tool to guide the treatment by optimizing the oral dosage in order to increase the AR rate.

Background: Therapeutic Drug Monitoring (TDM) represents one of the most promising tools in clinical practice to optimise antidepressant treatment. Nevertheless, little is still known regarding the relationship between clinical efficacy and serum concentration of venlafaxine (VEN). The aim of our study was to investigate the association between serum concentration of venlafaxine + O-desmethylvenlafaxine (SCVO) and antidepressant response (AR). Methods: 52 depressed outpatients treated with VEN were recruited and followed in a naturalistic setting for three months. Hamilton Depression Rating Scale-21 was administered at baseline, at month 1 and at month 3 to assess AR. SCVO was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCVO and AR. Results: Our results showed an association between AR and SCVO that follows a bell-shaped quadratic function with a progressive increase of AR within the therapeutic reference range of SCVO (i.e. 100–400 ng/mL) and a subsequent decrease of AR at higher serum levels. Discussion: This study strongly suggests that TDM could represent a more appropriate tool than the oral dosage to optimise the treatment with VEN. Specifically, highest efficacy might be achieved by titrating patients at SCVO levels around 400 ng/mL.

To report on: 1) the modification process occurred within the Psychiatric Service of Bolzano toward an early, intensive, specific and multimodal system of care for patients experiencing their first psychotic episode and their family members; 2) the 12-month clinical and social course of a sample of patients referred to the "Early Intervention Project".Longitudinal naturalist study evaluating the 12-month clinical and outcome of a cohort of first-episode psychosis patients consecutively referred to the "Early Intervention Project" implemented within the Psychiatric Service of Bolzano. Socio-demographic characteristics, housing situation and occupational status, interventions offered (medical intervention, psychotherapy, psychoeducation to family members, social intervention) and hospital admissions were drawn from electronic medical records. Levels of psychopathology and global functioning were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Global assessment of Functioning (GAF), respectively.During the first five years of activity (2012-2017) 116 patients had been referred to the Project. At 12 months 83.6%were still in charge, 7.76% moved to another area, 8.5% have abandoned the intervention. No significant difference in terms of age and gender was found between patients who remained in the project and those who lost contact. All patients had received specific integrated treatment; moreover, 16% had received intensive residential care. Notably, only 13.5% have had a hospital readmission over the 12 months of intervention. The PANSS total, positive and negative scores displayed significant reduction from baseline (BL) to follow-up (FU); in parallel, increase in GAF score from BL to FU was observed. All patients employed at BL were able to keep their job at FU; 17% of all patients unemployed at baseline were employed at FU.The "Early Intervention Project" implemented in Bolzano was found to ensure integrated, multidisciplinary and early treatment, as defined by the most recent international guidelines, which produced significant improvement in both clinical and social outcomes in a cohort of first-episode psychosis patients.

The global handling of the COVID-19 pandemic illustrates that most governments are lacking intergenerational public health solutions. Discontinuity of health care services, mental and physical burden of isolation and school closures increase various pathologies and may provoke long-term health damage amongst the youngest. Unbalanced generational approaches within health policies have been evident before the pandemic and will continue to be a global challenge as both acute and chronic threats due to environmental hazards and social disparities are increasing. Beyond the current crisis and in dealing with any public health threat, intergenerational approaches focused on the welfare of children and adolescents and the long-term impact on their lives are imperative and must be a core part in the development and implementation of public health policies.

To investigate pharmacokinetic correlates of clinical response in patients treated with once-monthly paliperidone palmitate (PP1M) injections at steady state. Plasma concentrations and dose-adjusted-plasma concentrations (C/D) of paliperidone from a naturalistic therapeutic drug monitoring (TDM) database were compared between responders and non-responders using the Clinical Global Impressions-Improvement scale (CGI-I) ratings. Analyses were based on the non-parametric Mann–Whitney U test and the Pearson Chi-squared test (χ2) with a significance level of 0.05. Subgroup analyses were performed separately in patients with schizophrenia spectrum, schizoaffective disorders and bipolar disorders. Comparing 93 responders with 80 non-responders, we detected no significant differences in the proportion of females, age, and body mass index (p’s ranging 0.18–0.83); there were more smokers in the group of non-responders (p = 0.04), which also included more patients with bipolar disorders (p = 0.014). Despite the lack of differences for prescribed PP1M doses and dose intervals (p = 0.42 and p = 0.11, respectively), non-responders had higher paliperidone plasma concentrations and C/D levels (p = 0.033 and p = 0.021, respectively). Subgroup analyses did not yield differences for paliperidone plasma and C/D levels between non-responders and responders with schizophrenia spectrum (p = 0.099 and p = 0.14, respectively) and bipolar disorders (p = 0.95 and p = 0.75, respectively); dose-adjusted plasma concentrations were higher in non-responders compared to responders with schizoaffective disorders (p = 0.039), while no differences were reported for plasma levels (p = 0. 15). Our results show that paliperidone plasma concentrations over injection doses may be associated with patterns of clinical response suggesting potential utility of TDM as part of PP1M-based maintenance treatment.

Introduction Major smoking effects have been reported for a series of psychotropic agents, mainly including substrates of CYP450 1A2, although smoking may also affect alternative metabolic pathways. To our knowledge, smoking effects on paliperidone pharmacokinetics have not been assessed yet. Methods We compared plasma concentrations of paliperidone as well as dose-corrected-plasma concentrations (C/D) from a naturalistic database between smokers and nonsmokers using nonparametrical tests, such as the Mann-Whitney U-test (MWU). Additionally, we compared light and heavy smokers with nonsmokers separately. Results Comparing 55 smokers with 37 nonsmokers treated with oral paliperidone, no differences in the percentage of females, age, body weight, body mass index, and daily paliperidone dose were reported (p=0.709 for χ2, p=0.26, p=0.38, p=0.67, and p=0.8 for MWU). No differences were detected in plasma concentrations or C/D values (p=0.50 and p=0.96 for MWU). Likewise, differences in daily dose, plasma concentrations, or C/D values were not significant between light smokers (n=17) and nonsmokers (p=0.61, p=0.81, and p=0.33 for MWU) or heavy smokers (n=22) and nonsmokers (p=0.874, p=0.38, and p=0.59; MWU in all cases). Discussion Paliperidone is not affected by smoking, and paliperidone dose-adjustments in smokers may not be necessary. This may be seen as an essential difference to risperidone, whose cytochrome-mediated metabolism might be affected by smoking.

Prospective memory (PM) is essential in everyday life because it concerns the ability to remember to perform an intended action in the future. This ability could be influenced by poor sleep quality, the role of which, however, is still being debated. To examine the role of sleep quality in PM in depth, we decided to perform a retrospective naturalistic study examining different clinical populations with a primary sleep disorder or comorbid low sleep quality. If sleep is important for PM function, we could expect poor sleep to affect PM performance tasks both directly and indirectly. We examined a total of 3600 nights, recorded using actigraphy in participants belonging to the following groups: primary insomnia (731 nights), narcolepsy type 1 (1069 nights), attention deficit hyperactivity disorder (152 nights in children and 239 in adults), severe obesity (232 nights), essential hypertension (226 nights), menopause (143 nights), healthy controls (808 nights). In a naturalistic activity-based PM task, each participant originally wore an actigraph around the non-dominant wrist and was requested to push the event-marker button at two specific times of day: bedtime (activity 1) and get-up time (activity 2). Each clinical group showed significantly lower sleep quality in comparison to the control group. However, only narcolepsy type 1 patients presented a significantly impaired PM performance at get-up time, remembering to push the event-marker button around half the time compared not only to healthy controls but also to the other clinical groups. Overall, the present results seem to point to sleep quality having no effect on the efficiency of a naturalistic activity-based PM task. Moreover, the data indicated that narcolepsy type 1 patients may show a disease-specific cognitive deficit of PM.

Objective: To conduct a systematic review of studies assessing the relationship between exposure to pesticides and ADHD or Autism Spectrum Disorder (ASD). Methods: Based on a pre-registered protocol in PROPSERO (CRD42018107847), we searched PubMed, Ovid databases, and ISI Web of Knowledge with no date/language/document type restrictions, up to May 2019. The Newcastle Ottawa Scale was used to assess study quality. Results: Among the 29 retained studies, 13 focused on ADHD, 14 on ASD, and two on both disorders. Ten studies reported a significant association between exposure to pesticides and ADHD/ADHD symptoms and 12 studies found a significant association with ASD/ASD traits. The strengths of the association and the possible confounders controlled for varied substantially across studies. Conclusion: Whilst there is some evidence suggesting a possible link between pesticides and ADHD/ASD, heterogeneity across studies prevents firm conclusions. We provide methodological indications for future studies.

Objective The quantification of antipsychotic levels in blood, also known as therapeutic drug monitoring (TDM), is a potentially useful tool of modern personalized therapy that can be applied to augment antipsychotic use and dosing decisions. The application of TDM for antipsychotics can be helpful in numerous challenging clinical scenarios, such as lack of therapeutic response, relapse, or adverse drug reactions (ADRs) related to antipsychotic treatment. The benefits of TDM may be particularly evident in the treatment of highly vulnerable patient subgroups, such as children, adolescents, pregnant women, and the elderly. The main aim of this article is to aid clinicians who routinely prescribe antipsychotics to successfully apply TDM in routine clinical practice in order to help optimize the efficacy and safety of those antipsychotics. Participants Participants were clinicians and researchers, members of the American Society of Clinical Psychopharmacology, and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (Association of Neuropsychopharmacology and Pharmacopsychiatry). Evidence TDM literature on antipsychotics was critically reviewed to provide a condensed clinical decision-making algorithm with therapeutic reference ranges for blood antipsychotic levels, within which patients are most likely to respond and tolerate treatment, although TDM is not equally recommended/supported for all antipsychotics. Consensus process A preliminary draft was prepared and circulated to the writing group members. Consensus was achieved in all cases, and resulting recommendations focused on following areas: steady-state and sampling time, levels of recommendations, indications, therapeutic reference ranges and laboratory alert levels, practical issues, and interpretation, as well as limitations. Conclusions The utilization of TDM as a tool for problem solving in antipsychotic treatment offers a unique method to improve safety and efficacy. This consensus statement summarizes essential information on the routine use of TDM for antipsychotics and encourages clinicians to perform TDM with the appropriate indications as part of the clinical decision-making process.

Workplace violence and aggression are receiving increasing attention, especially when perpetrated in at-risk services such as psychiatric and emergency departments. Many healthcare providers have been victims of verbal aggressions (VAs) and physical aggressions (PAs), as well as injuries (INs), at the hands of patients. We conducted a 1-year retrospective questionnaire-based survey to assess workplace violence and aggression experienced by staff working at the Psychiatric Service of the Health District of Bolzano-Bozen (Italy). We performed parametric statistics. Logistic regression estimated the size of the association between PA occurrence and staff characteristics. Our psychiatric service's employees were frequent victims (91.5%) of 1 or more aggression/injury in the previous year. VAs and INs showed comparable frequencies among the three sites of our service, that is, the inpatient (INP), the outpatient (OUTP), and the rehabilitation (REHAB) units, differently from PAs, which were more common at INP (p < 0.001). The logistic regression model showed that female sex, working at INP, and a shorter psychiatry work experience predicted PAs occurrence. Most of the staff felt they could benefit from aggression management. Findings show that VAs, PAs, and INs are common among our psychiatric service's employees and point to the need to provide staff training on de-escalation.

OBJECTIVES The history of electroconvulsive therapy (ECT) spans eight decades, over which period this method of treatment has been modernized. At the same time, however, the conflict between acceptance and rejection of ECT therapy remains unresolved today. This ambivalence is particularly noticeable in Italy, where the number of uses of ECT has been declining for several years. The aim of the present study is to examine the distribution and use of ECT in Italy today in comparison to 2009 and to analyze the factors that have influenced this downward development. METHODS A cross-sectional study using a standardized Italian-language questionnaire was conducted in 2017 to investigate the dissemination and practice of ECT in Italy. The study was addressed to all public and private hospitals providing ECT as a treatment. RESULTS Of the 145 mental health facilities in Italy, only 9 offered ECT. A total of 293 patients were treated with ECT within 1 year (mainly for depression). Rates for 3-year treatments in the centers yielded an uneven picture: 4 centers showed an increase in cases and just as many a decline. A north-south divide existed in terms of geographical distribution: centers were mainly located in the north in 2017. CONCLUSIONS The study shows that the dissemination and use of ECT have reached a historical low in Italy. It further documents the extent to which the use of ECT declined after 2009. Three factors that have accompanied this development are discussed. If this downward trend is to be reversed, it will be necessary to develop a new approach so as to engender a perception of ECT as a viable treatment option.

The present study was designed to shed light on a topic rarely explored and to suggest possible ways to detect risk factors for the presence of suicidal ideation and behaviors in a sample of adult patients with Attention-Deficit Hyperactivity Disorder (ADHD). This study also explored the association between ADHD, affective temperaments, the presence of hypomania symptoms, and suicide risk. We hypothesized that (compared to healthy controls) (1) patients with adult ADHD would report more negative affective temperaments and more hypomania symptoms and (2) that they would have a higher suicide risk. The participants included 63 consecutive adult inpatients (18 women, 45 men) with ADHD and 69 healthy controls (42 women, 22 men). All participants were administered the Wender Utah Rating Scale (WURS), the Hypomania Check-List-32 (HCL-32), the Mood Disorder Questionnaire (MDQ), the Temperament Evaluation for Memphis, Pisa, Paris, and San Diego (TEMPS-A), and the Columbia-Suicide Severity Rating Scale (C-SSRS). Forty-six percent of the ADHD patients had an Axis 1 comorbid disorder. ADHD patients (compared to controls) more often reported suicidal ideation (46.0% vs. 5.9%, one-way Fisher exact test p &lt, 0.001, phi = 0.46). ADHD patients and the controls also significantly differed in all the scales administered (with Cohen&rsquo, s d between 0.92&ndash, 4.70), except for the TEMPS-A Hyperthymia scale. A regression model indicated that ADHD was independently associated with higher scores of a negative temperaments/hypomania factor (Odd Ratio = 14.60) but not with suicidal ideation. A high incidence of suicidal ideation, comorbid psychiatric disorders, and negative affective temperaments was reported in adult ADHD patients, and clinicians should routinely assess risk factors for suicide among these patients.

The observation that people with schizophrenia misattribute the source of their own actions has led to the hypothesis that they suffer from altered sensorimotor processes underlying sense of agency. Furthermore, rubber hand studies suggest an abnormal experience of embodiment in schizophrenia. However, this latter finding is based on a procedure that elicits ownership sensations for a fake hand by visuo-tactile stimulation, leaving the agency subcomponent of embodiment relatively untouched. By using a visuo-motor version of the embodiment illusion able to actively elicit also sense of agency for an alien hand, we tested whether the putative sensorimotor deficits are also involved in altering embodiment sensations in schizophrenia. Subjective (questionnaire) and perceptual (forearm bisection performance) indexes of the embodiment illusion were collected. Differently from controls, both the explicit agency component and the implicit body metrics update were not modulated by the extent of visuo-motor congruency in participants with schizophrenia. We conclude that motor prediction and/or temporal binding window impairments may alter the feeling of embodiment and body representation in schizophrenia.

Objective Adult and children attention deficit/hyperactivity disorder (ADHD) share similar symptoms and responses to drugs such as methylphenidate (MPH). Yet, in Europe, these drugs remain unlicensed for adults. We aimed to assess the effects of an acute MPH challenge on the four dimensions concentration, impulsivity, tension, and general well-being in ADHD adults, and identify predictors of improvement. Methods Therapeutic Drug Monitoring was performed to measure MPH plasma levels. A Visual Analogue Scale was administered to patients before and after the acute MPH challenge to measure self-reported changes in the four dimensions. Results After the acute MPH challenge, our 71 patients showed significant improvement in concentration and tension. The MPH challenge dose correlated with lower patients' age, greater side effects, increased concentration (p = .008) and decreased tension (p = .001). At multiple linear regression MPH plasma levels and absence of postdose side effects predicted concentration improvement, MPH plasma levels predicted tension improvement. MPH plasma levels were significantly higher in patients who reported an improvement in concentration, tension, and impulsivity compared to nonimprovers (p's from .001 to .004). Conclusions These findings point to the efficacy of MPH challenge in improving concentration and tension in adult ADHD, thus emphasizing the need for a broader treatment access for these patients.

Attention deficit/hyperactivity disorder (ADHD) often persists into adulthood. Although its persistence and relative high prevalence, ADHD in adults is often underdiagnosed and undertreated in Italy, leading to poor clinical and functional outcomes, and higher costs of illness. The aims of the study were to identify the Italian mental health services for ADHD in adults, describe the diagnostic and treatment procedures they follow, and compare this offer with the recommendations of the German and English guidelines. The centres, that adopt a clinical and assessment protocol for adult ADHD diagnosis (carried out by specifically trained personnel) and prescribe pharmacological treatment for adult ADHD, were selected from the list of accredited services provided by the Appendix B.2 of the ISTISAN 16/37 Reports of the ISS. An ad-hoc survey including open-ended and close-ended questions was sent to each selected centre in February 2020. The overall picture resulting from the data analysis was compared with the recommendations of the German and English guidelines. The present survey shows that only a few centres are specialised in the diagnosis and treatment of ADHD in adults in Italy. Furthermore, there are no national guidelines for adult ADHD in Italy. The collected data also suggest that there is no a unified practice shared by the Centres both for the patient's transition from child and adolescent to adult mental health services and for the diagnostic-therapeutic process. It is therefore crucial to create specific protocols and develop national guidelines to better identify and diagnose ADHD in adults and provide targeted and more efficient multimodal treatments.

Therapeutisches Drug-Monitoring (TDM) umfasst die Quantifizierung und die Interpretation von Serum- oder Plasmakonzentrationen von Arzneistoffen im Blut, um die Pharmakotherapie zu optimieren. TDM ist ein Werkzeug, mit dem sich die hohe interindividuelle Variabilitat der Pharmakokinetik von Patienten identifizieren lasst und es ermoglicht somit eine personalisierte Pharmakotherapie. Im September 2017 veroffentlichte die Arbeitsgruppe Therapeutisches Drug-Monitoring der Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) ein Update der TDM-Konsensusleitlinien. In diesem Artikel sollen die wesentlichen Inhalte fur die klinische Praxis in der Psychiatrie und Neurologie zusammengefasst werden.