Therapeutic Appropriateness of Cariprazine in the Management of Schizophrenia: Experts' Opinion using a Delphi Approach.

BACKGROUND: Schizophrenia is a psychiatric disorder whose therapeutic objectives are aimed at reducing symptoms and improving patient's quality of life. First- and second-generation antipsychotics present numerous side effects. Recently introduced in the treatment of schizophrenia, cariprazine has shown to improve positive and negative symptoms as well as cognitive impairment, with good tolerability. OBJECTIVE: To assess the level of consensus among Italian psychiatrists in relation to the use of cariprazine in the treatment of schizophrenia by using the Delphi technique. METHOD: A Delphi study was undertaken between January and July 2022. Two questionnaires were consecutively sent to a panel of 97 psychiatrists from all over Italy, of which 81 actively participated, anonymously, in at least one of the two consultations with a sufficiently high response rate (83%). RESULTS: Broad consensus in terms of the efficacy and safety of cariprazine in the treatment of schizophrenia during all phases of the disorder. The young first-episode schizophrenia patient with or without substance abuse seems to be an excellent candidate for cariprazine therapy. In addition, the lack of side effects makes cariprazine a suitable drug for adult and elderly patients with schizophrenia. However, there is still limited experience with the use of cariprazine, along with little knowledge of the most recent real-life data. CONCLUSION: These results could encourage wider dissemination of evidence-based practices with the final aim of optimizing the clinical use of cariprazine in patients with schizophrenia.

The pharmacological management of gambling disorder: if, when, and how.

INTRODUCTION: Gambling disorder (GD) consists of a persistent, recurrent pattern of gambling that is associated with substantial distress or impairment. The etiology is multifactorial. GD frequently co-occurs with other psychiatric disorders and is often untreated. Different psychosocial interventions, particularly cognitive-behavioral therapy, are useful in the treatment of GD. Pharmacological therapy may also be helpful . No formal guidelines exist, and the management of the disease is often guided by few clinical elements. AREAS COVERED: A literature search was performed using PubMed, Scopus, and Web of Science databases about treatment options for GD, considering both psychosocial treatments and available pharmacological ones. EXPERT OPINION: The authors address whether and when it is appropriate to initiate pharmacological treatment for GD. They focus on providing clinicians with guidance on how to approach patients with GD in those situations where pharmacological therapy may be necessary. The reasons for the clinician to start thinking about a medication are examined. As specific traits in the psychopathology of GD may be managed with a strategic choice of the pharmacologic agent, the different available options are analyzed on the basis of their potential usefulness in GD. Issues that remain open about the pharmacological management of GD are summarized.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression.

BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD. OBJECTIVES: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch. METHODS: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. RESULTS: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch. CONCLUSIONS: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.

Clinical and psychological factors associated with resilience in patients with schizophrenia: data from the Italian network for research on psychoses using machine learning.

BACKGROUND: Resilience is defined as the ability to modify thoughts to cope with stressful events. Patients with schizophrenia (SCZ) having higher resilience (HR) levels show less severe symptoms and better real-life functioning. However, the clinical factors contributing to determine resilience levels in patients remain unclear. Thus, based on psychological, historical, clinical and environmental variables, we built a supervised machine learning algorithm to classify patients with HR or lower resilience (LR). METHODS: SCZ from the Italian Network for Research on Psychoses (N = 598 in the Discovery sample, N = 298 in the Validation sample) underwent historical, clinical, psychological, environmental and resilience assessments. A Support Vector Machine algorithm (based on 85 variables extracted from the above-mentioned assessments) was built in the Discovery sample, and replicated in the Validation sample, to classify between HR and LR patients, within a nested, Leave-Site-Out Cross-Validation framework. We then investigated whether algorithm decision scores were associated with the cognitive and clinical characteristics of patients. RESULTS: The algorithm classified patients as HR or LR with a Balanced Accuracy of 74.5% (p < 0.0001) in the Discovery sample, and 80.2% in the Validation sample. Higher self-esteem, larger social network and use of adaptive coping strategies were the variables most frequently chosen by the algorithm to generate decisions. Correlations between algorithm decision scores, socio-cognitive abilities, and symptom severity were significant (pFDR < 0.05). CONCLUSIONS: We identified an accurate, meaningful and generalizable clinical-psychological signature associated with resilience in SCZ. This study delivers relevant information regarding psychological and clinical factors that non-pharmacological interventions could target in schizophrenia.

Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature.

BACKGROUND: Ibogaine and noribogaine are psychedelic substances with dissociative properties naturally occurring in plants of the Apocynaceae family. Research has shown their efficacy in treating substance use disorders (SUD), particularly in opiate detoxification, but their efficacy and toxicity are still unclear. OBJECTIVE: This review aims to assess the anti-addictive role of ibogaine and evaluate its side effects. METHODS: A systematic literature review was conducted on the 29th of November 2021 using PubMed, Scopus and Web of Science databases through the following search strategy: ("Ibogaine" OR "Noribogaine") AND ("SUD" OR "substance use disorder" OR "craving" OR "abstinence" OR "withdrawal" OR "addiction" OR "detoxification") NOT animal NOT review NOT "vitro." The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed for data gathering purposes. Research methods were registered on PROSPERO (CRD42021287034). RESULTS: Thirty-one articles were selected for the systematic revision, and two were considered for analysis. The results were organised according to the type of study: case reports/case series, randomised- controlled trials (RCTs), open-label, survey and observational studies. The main outcomes were related to the anti-addictive effect of ibogaine and its cardiac toxicity. A meta-analysis of side effects was conducted using RevMan 5.4 software, showing a significant risk of developing headaches after ibogaine/noribogaine treatment. CONCLUSION: The results show some efficacy of ibogaine in the treatment of SUDs, but its cardiotoxicity and mortality are worrying. Further studies are needed to assess its therapeutic efficacy and actual safety.

Knowledge and Use of Over-the-counter Drugs in Italy: An Exploratory Survey-based Study in the General Population.

BACKGROUND: During the past decade, the misuse of over-the-counter (OTC) medicines has become a global public health concern, especially among young people. In this study, we aimed to explore the OTC consumption and related misuse in Italy and identify the demographic characteristics of people/individuals involved in this phenomenon, understanding eventual risk factors. METHODS: The study consisted of an anonymous online survey distributed by direct contact and via the Internet between June-November 2021 to the general population living in Italy. Descriptive statistics were reported, and binary regression analyses were performed to identify risk factors for lifetime misuse of OTC. The University of Hertfordshire approved the study (aLMS/SF/UH/02951). RESULTS: The final sample size was composed of 717 respondents. The sample was mainly represented by female (69.3%) students (39.9%) in the 20-25 years age group (30.0%). Based on the survey responses, study participants were divided into two groups according to the presence/absence of OTC abuse/misuse (127 versus 590), which were compared for possible predictors of OTC diversion. Multivariate regression showed that OTC abuse/misuse was associated with the knowledge of the effects of OTC [odds ratio/OR = 2.711, 95%Confidence Interval/CI 1.794-4.097, p <0.001]. On the contrary, the educational level appeared to be a protective factor [OR = 0.695, 95%CI 0.58-0.94, p = 0.016]. CONCLUSION: Although, according to our data, the phenomenon of OTC abuse appeared to be limited, increasing attention is needed because of possible underestimation and high-risk outcomes. Preventive strategies, including simplified access to information, may play a key role in limiting OTC misuse.

Facebook and Suicidal Behaviour: User Experiences of Suicide Notes, Live-Streaming, Grieving and Preventive Strategies-A Scoping Review.

BACKGROUND: Facebook represents a new dimension for global information sharing. Suicidal behaviours and attempts are increasingly reported on Facebook. This scoping review explores the various aspects of suicidal behaviours associated with Facebook, discussing the challenges and preventive measures. METHODS: PubMed, Google Scholar, and Scopus were searched for related articles published in English up to October 2021, using different combinations of "Facebook" and "suicide". A group of experts comprising consultant psychiatrists screened the records and read the full-text articles to extract relevant data. Twenty-eight articles were chosen as relevant and included in the review under four selected themes. RESULTS: Facebook impacts on suicidal behaviours in different aspects. Announcing suicides through sharing notes or personal information may lead to the prediction of suicide but be harmful to the online audience. Live-streaming videos of suicide is another aspect that questions Facebook's ability to monitor shared contents that can negatively affect the audience. A positive impact is helping bereaved families to share feelings and seek support online, commemorating the lost person by sharing their photos. Moreover, it can provide real-world details of everyday user behaviours, which help predict suicide risk, primarily through novel machine-learning techniques, and provide early warning and valuable help to prevent it. It can also provide a timeline of the user's activities and state of mind before suicide. CONCLUSIONS: Social media can detect suicidal tendencies, support those seeking help, comfort family and friends with their grief, and provide insights via timelining the users' activities leading to their suicide. One of the limitations was the lack of quantitative studies evaluating preventative efforts on Facebook. The creators' commitment and the users' social responsibility will be required to create a mentally healthy Facebook environment.

Efficacy of Noninvasive Brain Stimulation on Borderline Personality Disorder Core Symptoms: A Systematic Review.

Although psychotherapy is the first-line treatment of borderline personality disorder (BPD), psychopharmacological agents have not been approved yet. Modulating brain functions with noninvasive brain stimulation (NIBS) interventions, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), may have a role in the treatment of BPD. In light of the limited knowledge available and the emerging interest in the possible role of NIBS as a therapeutic tool, the authors' main aim is to systematically review the literature on the effect of both rTMS and tDCS on BPD symptoms, specifically affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual difficulties. The review process was conducted in accordance with PRISMA guidelines. The research methods were registered on PROSPERO (id code CRD42020209491). Eleven studies were included in the review. Despite the limited number of studies retrieved, preliminary data showed an improvement in all domains. Further studies are needed to understand potential long-term advantages of NIBS.

Evolution of antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia in the real-life: A 4-year follow-up naturalistic study.

Previous studies have shown, although not consistently, that first generation antipsychotics (FGA) are associated with a prevalence of extrapyramidal symptoms (EPS) higher than second generation antipsychotics (SGA). We assessed the prevalence and the incidence of antipsychotic-induced EPS in a large sample of community-dwelling Italian persons with schizophrenia before and after a 4-year naturalistic treatment, to shed light on their natural evolution and to identify possible predicting factors. EPS and psychopathology were assessed in 571 subjects with schizophrenia before (baseline) and after 4-year follow-up. Patients underwent treatment with SGA and/or FGA according to the referring clinicians' judgment. Relationships between EPS and psychopathology were assessed by network analysis, while a linear multiple regression investigated factors correlated to the presence of EPS at follow-up. EPS were significantly more frequent in the FGA- than in the SGA-treated group, and patients with EPS presented a more severe psychopathology. Parkinsonism was directly and positively connected with poor emotional expression at baseline and with poor emotional expression and disorganization at follow-up. Over the 4-year follow-up, emergent EPS were more frequent in FGA-treated patients, while relieved EPS occurred more frequently in SGA-treated persons. The presence of EPS at follow-up was significantly associated with EPS at baseline, illness duration, antipsychotic generation and the daily dose of antipsychotic medications. After a 4-year naturalistic treatment, EPS disappeared more frequently in SGA-treated patients, while they emerged more frequently in FGA-treated individuals. Therefore, although SGA did not eliminate the risk of EPS, these drugs seem to be associated to a more favorable EPS natural evolution.

Online 12-step groups during the Covid-19 pandemic: A patient's perspective.

Background: Following the Covid-19 pandemic, lockdown strategies have been adopted by many Governments worldwide to stop the spread of the virus. Twelve-step programs for people with substance use disorders (SUDs) as Narcotics Anonymous (NA) experienced forced interruption as well, in some cases organizing online meetings to continue their activities. The purpose of this article is to reflect on concerns and advantages of online setting for 12-step groups. Methods: We report the experience of an Italian NA participant attending for the first time an online NA group during the Covid-19 pandemic. Results: The strengths and limitations of the online setting, showing up from the living voice of this participant, are expressed in the light of the present pandemic situation. Together with the general advantages derived from telehealth technologies, specific benefits of the virtual setting for 12-step programs are shown. Concerns are also discussed, as those related to privacy and social presence. Conclusions: The case highlights many possibilities of the online setting for 12-step programs. On the other hand, it suggests the critical importance of in-person groups to accompany the recovery process. Future outcome research is needed about the combination of these approaches.

Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study).

Background: 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. Objectives: Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services. Methods: 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. Results: 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. Limitations: 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. Conclusions: 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.

Legacy of neuropsychiatric symptoms associated with past COVID-19 infection: A cause of concern.

Although primarily affecting the respiratory system, growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Acute and sub-acute neuropsychiatric manifestations of coronavirus disease 2019 (COVID-19) disease and their mechanisms are better studied and understood currently than they had been when the pandemic began; however, many months or years will be necessary to fully comprehend how significant the consequences of such complications will be. In this editorial, we discuss the possible long-term sequelae of the COVID-19 pandemic, deriving our considerations on experiences drawn from past coronaviruses' outbreaks, such as the SARS and the middle east respiratory syndrome, and from the knowledge of the mechanisms of neurotropism and invasiveness of SARS-CoV-2. Acknowledging the global spread of COVID-19 and the vast number of people affected, to date amounting to many millions, the matter of this pandemic's neuropsychiatric legacy appears concerning. Public health monitoring strategies and early interventions seem to be necessary to manage the possible emergence of a severe wave of neuropsychiatric distress among the survivors.

Gender differences in attention deficit hyperactivity disorder: an update of the current evidence.

The attention deficit hyperactivity disorder (ADHD) in women has recently received considerable attention, as research has shown an underestimation of the disorder in females, due to a difference in presentation compared to males: females have a higher risk of having ADHD, without those "disruptive" symptoms that determine the request for help. The purpose of the present narrative review is to identify the neglected clinical problems in the diagnostic and therapeutic intervention of women with ADHD and to analyze the associated comorbid problems. The conducted PubMed search and the relevant literature review on the topic show that the impairment of ADHD in women is underestimated due to the different ways the phenomenon manifests compared to traditional male's symptoms. This underestimation consequently leads to an inadequate treatment and has negative repercussions on the social context in which women are involved in.

COVID-19 and first manic episodes: a systematic review.

Sars-CoV-2 is a respiratory virus that can access the central nervous system, as indicated by the presence of the virus in patients' cerebrospinal fluid and the occurrence of several neurological syndromes during and after COVID-19. Growing evidence indicates that Sars-CoV-2 can also trigger the acute onset of mood disorders or psychotic symptoms. COVID-19-related first episodes of mania, in subjects with no known history of bipolar disorder, have never been systematically analyzed. Thus, the present study assesses a potential link between the two conditions. This systematic review analyzes cases of first appearance of manic episodes associated with COVID-19. Clinical features, pharmacological therapies, and relationships with pre-existing medical conditions are also appraised. Medical records of twenty-three patients fulfilling the current DSM-5 criteria for manic episode were included. Manic episodes started, on average, after 12.71±6.65 days from the infection onset. Psychotic symptoms were frequently reported. 82.61% of patients exhibited delusions, whereas 39.13% of patients presented hallucinations. A large discrepancy in the diagnostic workups was observed. Mania represents an underestimated clinical presentation of COVID-19. Further studies should focus on the pathophysiological substrates of COVID-19-related mania and pursue appropriate and specific diagnostic and therapeutic workups.

Relationship between Health-Anxiety and Cyberchondria: Role of Metacognitive Beliefs.

PURPOSE: The current study was designed to examine the relationship between health anxiety, cyberchondria (its constructs), and metacognitive beliefs. In addition, it also evaluated the moderating role of metacognitive beliefs in this relationship. DESIGN AND METHOD: The present study used the purposive sampling technique to acquire a sample of (N = 500) adults, among them (N = 256) women and (N = 244) men, and the age of the sample ranged from 20 to 50 years. Short Health Anxiety Inventory, Cyberchondria Severity Scale, and Metacognitions Questionnaire-Health Anxiety were used to operationalize the present study variables. FINDINGS: The descriptive statistics revealed that all instruments have good psychometric properties, as Cronbach's alpha coefficients for all scales are ≥0.70. In addition to this, the Pearson correlation showed that all variables of the present study have a significant positive correlation with each other. Furthermore, the regression analysis described that health anxiety and metacognitive beliefs (biased thinking and beliefs about uncontrollable thoughts) were the significant positive predictors of cyberchondria. Moreover, moderation analysis showed that metacognitive beliefs significantly strengthened the association between health anxiety and cyberchondria and its constructs. PRACTICAL IMPLICATIONS: The present study will help medical practitioners to understand how metacognitive beliefs and health anxiety can cause an increase in cyberchondria. This will help them to design better treatment plans for people with cyberchondria.

Analysis of female enrollment in clinical trials for alcohol and substance use disorders: Is it time for sex-informed pharmacotherapy?

BACKGROUND: Women represent an increasing number of individuals with alcohol and substance use disorders (ASUDs), and sex-differences might affect results of interventional clinical trials (CTs). We aim at assessing the proportion of women and the reporting of sex-stratified and female-specific data in CTs for ASUDs. METHODS: We extracted data from ClinicalTrials.gov on Phase 1-3 CTs of investigational drugs for ASUDs conducted from 2000 to 2021 and identified articles related to these trials. We determined the average proportions of women enrolled per trial overall, over time, and by disease area and trial phase. Next, we calculated the proportion of articles reporting sex-stratified and female-specific data. RESULTS: In the 234 CTs identified, the overall proportion of women was 33.4% [95% CI: 32.7%-33.9%]), with an increasing temporal trend. Women's participation was higher in CTs of investigational drugs for tobacco (43.5% [95% CI: 42.4% -44.5%]) and alcohol use disorder (35.9% [95% CI: 34.54%-37.21%]), and closely mirrored their representation in the disease populations (46% and 37%). Conversely, women were underrepresented in clinical trials of drugs for cocaine and stimulant use disorders (25.8% [95% CI: 24.6%-27.1%]) and opioid use disorders (25.9% [95% CI:24.2%-27.7%]). Nine publications reported sex-stratified data in the method and/or result section, whereas none documented female-specific data. CONCLUSIONS: Enrollment of women in ASUDs CTs has increased over time but remains low in several disease areas. This, together with the low rates of reporting of sex-stratified data, calls for an adequate inclusion of sex in the design and analysis of CTs for ASUDs.

What role for cognitive remediation in the treatment of depressive symptoms? A superiority and noninferiority meta-analysis for clinicians.

BACKGROUND: Cognitive remediation (CR) is a promising technique in the treatment of the cognitive dimension of depression. The present study evaluated the potential of CR in treating depressive symptoms and provides practical information about its usefulness in clinical settings. METHODS: We performed two meta-analyses of published randomized (and nonrandomized) clinical trials, comparing CR to control conditions in subjects with current depressive symptomatology. The superiority meta-analysis aimed to determine the superiority of CR when compared with placebo/waiting list interventions and its efficacy when used as an augmentation therapy. The noninferiority meta-analysis determined whether CR had noninferior efficacy compared with standard antidepressant interventions. RESULTS: CR was found to significantly improve depressive symptomatology in the superiority meta-analysis (CR: n = 466, control n = 478). Moreover, CR seemed to be noninferior to standard antidepressant interventions (CR: n = 230, control n = 235). CR was more effective when addressing hot (vs. cold) cognition, when involving younger patients (i.e., <30 years), and in the case of mild-moderate (vs. severe) depression. CONCLUSIONS: CR should be considered an augmentation treatment to improve treatment outcomes in depressed subjects, especially among young individuals. Interventions addressing hot cognition seem to be the most promising.

Physical Activity and Exercise Addiction During the Covid-19 Pandemic in Italy.

Severe restrictive measures were implemented globally to limit the spread of the Covid-19 pandemic leading to significant lifestyle changes and impacting on both the physical and the mental health of citizens. Caught by the fear of getting sick, some individuals have adopted behaviors which favored the development of exercise addiction (EA). Our aim was to evaluate physical activity habits and the risk of EA in the general Italian population during phase 1 of the lockdown. The role of appearance anxiety (AA), self-compassion, and use of performance and image enhancing drugs (PIEDs) as predictors of EA development were investigated. A comparison between physically active subjects with the inactive ones was also included. Between April and May 2020, an online survey was conducted across Italy. Nine hundred thirty-six answers were collected. The rate of EA in the physically active sample (782 subjects) was 4.1%. The physically active group showed higher SCS scores and a greater use of PIEDs. Of the physically active participants, 84.2% reported variations in their fitness routine. Perceived benefit of exercising resulted significantly higher in those with EA. Subjects with EA reported stronger motivation in engaging in physical activity as for "physical wellness," "psychological well-being," and "sexual attractiveness and confidence in relationship." A higher level of AA, a lower level of self-compassion, and a higher perceived benefit of exercising during lockdown were all significant predictors for the presence of EA. Our findings suggest that the fear of getting sick from Covid-19, combined with radical changes in the lifestyles induced by the lockdown and individual personological characteristics, can favor the development of EA and related phenomena in the general population.