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.

Long-acting paliperidone in Ekbom's syndrome in Lewy body dementia: A case report.

Introduction: Ekbom Syndrome (ES) is characterised by fixed, delusional beliefs that one's body is infested by parasites or other vermin in absence of supporting clinical evidence. Antipsychotic (AP) treatment, including long-acting injectable (LAI) AP in subjects with poor compliance, is prescribed to manage behavioural and psychotic symptomatology. Objectives: We describe a 70-year-old woman who was hospitalised after experiencing new-onset delusions of infestation with visual and tactile hallucinations that led to bizarre behaviours and progressive social withdrawal. Methods: She was diagnosed with ES and was initially treated with risperidone 3 mg; however, due to poor compliance and a lack of insight, she was switched to LAI palmitate paliperidone (LAI-PP). She was followed up for 8 months, administering Positive and Negative Syndrome Scale, Montreal Cognitive Assessment, Global Assessment of Functioning, Brief Psychiatric Rating Scale, neurocognitive assessment, and neuroimaging. Results: After a progressive cognitive deterioration, she was diagnosed with an ES secondary to Lewy body dementia (DLB). Conclusion: The LAI-PP treatment determined a complete clinical remission of psychotic symptoms despite the emergence of an iatrogenic akinetic-rigid syndrome. The delay of confirmatory neurological diagnosis, the associated risky behaviours of the patient, and poor treatment adherence led clinicians to prescribe LAI-PP following a good clinical response to oral paliperidone. However, in the case of a suspected DLB diagnosis, the prescription of an LAI-PP as a first-line strategy should be carefully evaluated.

Fear and anxiety related to COVID-19 pandemic may predispose to perinatal depression in Italy.

The COVID-19 pandemic situation significantly affected the mental health of the general and clinical population. However, few studies investigated which COVID-19-related psychopathological determinants may predispose to perinatal depression. We evaluated the impact of COVID-19 related anxiety and fear on perinatal depression in Italy. We retrospectively screened 184 perinatal outpatients afferent to Perinatal Mental Health outpatient service, during March 2020-March 2021, by administering the Edinburgh Postnatal Depression Scale (EPDS), the Fear of COVID-19 (FCV-19-S) and the Coronavirus Anxiety Scale (CAS). Among these, 85 patients agreed to be recruited in the present study. The mean EPDS score was 9.0, experiencing a clinically relevant perinatal depression in 45.7% of the sample. The mean FCV-19-S score was 15.0 and CAS was 1.7. Linear regression analyses demonstrated that FCV-19-S and CAS scores statistically significantly predicted EPDS total scores. A positive significant correlation was reported between FCV-19-S and EPDS and between CAS and EPDS. During the COVID-19 pandemic, women in their perinatal period, independently of previous psychiatric history, experienced increased levels of anxiety, fear and psychological distress, due to subsequent isolation, quarantine, lockdown and deprivation of their normal social support. Further preventive and screening strategies should be implemented in order to early identify at-risk pregnant and puerperal women during the COVID-19 pandemic.

Recognizing, Managing and Treating Acute Agitation in Youths.

Acute agitation is common in youths presenting to emergency departments, and, in some cases, may escalate into aggression and violence. Therefore, acute agitation in youths should be immediately and appropriately recognized and treated to avoid the consequences of its escalation. Agitation is widespread in youths, reported in around 7% of all youths admitted to emergency departments due to psychiatric reasons. Overall, the most frequent causes of youth acute agitation include the exacerbation of neurodevelopmental disorders, such as ADHD, autism, or intellectual disabilities, or the onset of mood and psychotic disorders. Substance abuse is also common in adolescents and young adults with acute agitation. Management of agitation should be individualized, multidisciplinary, and collaborative. Along with a diagnostic assessment, the needs of the young patients should be understood and addressed, and de-escalation strategies should be immediately prompted. Rapid recognition and management are warranted, in order to assure the safety of the patient and healthcare staff jeopardized by the acute crisis. Firstly, environmental and de-escalation strategies should be acted with the aim to reduce agitation and, if possible, avoid the use of physical restraint. In case these strategies fail to succeed, pharmacological treatment should be rapidly implemented. Although youth agitation and aggression is transdiagnostic, prior diagnosis of psychiatric disorder should guide the choice of the tranquilizing medication whenever possible. This review will examine these aspects in detail and provide guidance on how to recognize, manage, treat and resolve acute agitation in youths.

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.

A case report of clozapine-treatment-resistant schizophrenia successfully managed with brexpiprazole combination therapy.

Clozapine-resistant schizophrenia (CRS) occurs in 40%- 70% of clozapine-treated schizophrenic patients. Hereby we describe a 20-year-old CRS subject with comorbid cannabinoid use disorder, successfully treated with clozapine-brexpiprazole combination, subsequently switched to clozapine plus long-acting injectable aripiprazole.

Depressive and Anxious Temperaments as Predictors of Late Onset Bipolar Disorder? Preliminary Results of a "Real World" Exploratory Study.

INTRODUCTION: Bipolar disorder (BD) onset typically occurs between 15 and 30 years, being diagnosed under the age of 50 in 90% of cases, named "non-late onset BD" (non-LOBD). However, clinical observation of late-onset BD (LOBD) raised some concern regarding a differential psychopathological pattern, outcomes and treatment, including a specific affective temperament vulnerability. Therefore, an exploratory study in the "real world" was carried out by investigating psychopathological and temperamental features of a psychogeriatric cohort of LOBD and non-LOBD subjects. METHODS: A total of 180 patients affected with BD-I, BD-II, and Cyclothymic Disorder were screened in a Mood Disorder Outpatient Service, during the timeframe January 2019-August 2021. Out of 78 enrolled outpatients, 66 (33 non-LOBD, 33 LOBD) were recruited, by the retrospective collection of sociodemographic, cognitive, psychopathological and clinical assessment, including the short-version of the Temperament Evaluation of Memphis, Pisa, and San Diego (TEMPS-M). RESULTS: LOBD is significantly associated with higher rates of BD-II diagnosis (χ2 = 27.692, p < 0.001), depressive episodes (p = 0.025), mixed states (p = 0.009), predominant depressive and anxious affective temperaments (p < 0.001). Non-LOBD is significantly associated with higher endocrinological (χ2 = 6.988, p = 0.008) and metabolic comorbidity (χ2 = 5.987, p = 0.014), a diagnosis of BD-I, manic episodes, and predominant hyperthymic affective temperaments (p = 0.001). GDS (p < 0.001) and MSRS (p = 0.005) scores were significantly higher in LOBD. CONCLUSION: Further longitudinal studies with larger sample sizes and a control group are needed to determine whether LOBD may represent a distinct psychopathological entity from non-LOBD and evaluate differences (if any) in terms of prognosis and treatment between non-LOBD and LOBD.

A Preliminary Italian Cross-Sectional Study on the Level of Digital Psychiatry Training, Knowledge, Beliefs and Experiences among Medical Students, Psychiatry Trainees and Professionals.

The COVID-19 pandemic led to the implementation of digital psychiatry (DP), resulting in the need for a new skilled healthcare workforce. The purpose of this study was to investigate the level of training, knowledge, beliefs, and experiences of young mental health professionals and medical students in DP. An ad hoc cross-sectional survey was administered and descriptive analyses, Student's t and ANOVA tests were conducted, together with an exploratory factor analysis, bivariate correlations and linear regression. Most of the sample (N = 239) declared that DP was never discussed within their academic training (89.1%), mainly revealing an overall lack of knowledge on the issue. Nevertheless, subjects mostly declared that DP represents a valuable therapeutic tool in mental health (80%) and that their training should include this topic (54.4%). Moreover, most subjects declared that digital interventions are less effective than face-to-face ones (73.2%), despite the emerging evidence that being trained in DP is significantly associated with the belief that digital and in-person interventions are comparable in their effectiveness (p ≤ 0.05). Strong positive correlations were found between the knowledge score (KS) and perceived significance index (PSI) (r = 0.148, p < 0.001), and KS and Digital Psychiatry Opinion (DPO) index (r = 0.193, p < 0.001). PSI scores statistically significantly predicted KS total scores (F(1, 237) = 5.283, R2 = 0.022, p = 0.022). KS scores statistically significantly predicted DPO total scores (F(1, 237) = 9.136, R2 = 0.037, p = 0.003). During the current pandemic, DP represented an ideal response to the forced physical distancing by ensuring the advantage of greater access to care. However, this kind of intervention is still uncommon, and mental health professionals still prove to be skeptical. The lack of formal training on DP during the academic years could be a limiting factor.

COVID-19-Related Social Isolation Predispose to Problematic Internet and Online Video Gaming Use in Italy.

COVID-19 pandemic and its related containment measures have been associated with increased levels of stress, anxiety and depression in the general population. While the use of digital media has been greatly promoted by national governments and international authorities to maintain social contacts and healthy lifestyle behaviors, its increased access may also bear the risk of inappropriate or excessive use of internet-related resources. The present study, part of the COVID Mental hEalth Trial (COMET) study, aims at investigating the possible relationship between social isolation, the use of digital resources and the development of their problematic use. A cross sectional survey was carried out to explore the prevalence of internet addiction, excessive use of social media, problematic video gaming and binge watching, during Italian phase II (May-June 2020) and III (June-September 2020) of the pandemic in 1385 individuals (62.5% female, mean age 32.5 ± 12.9) mainly living in Central Italy (52.4%). Data were stratified according to phase II/III and three groups of Italian regions (northern, central and southern). Compared to the larger COMET study, most participants exhibited significant higher levels of severe-to-extremely-severe depressive symptoms (46.3% vs. 12.4%; p < 0.01) and extremely severe anxiety symptoms (77.8% vs. 7.5%; p < 0.01). We also observed a rise in problematic internet use and excessive gaming over time. Mediation analyses revealed that COVID-19-related general psychopathology, stress, anxiety, depression and social isolation play a significant role in the emergence of problematic internet use, social media addiction and problematic video gaming. Professional gamers and younger subjects emerged as sub-populations particularly at risk of developing digital addictions. If confirmed in larger and more homogenous samples, our findings may help in shedding light on possible preventive and treatment strategies for digital addictions.

Aripiprazole LAI two-injection start in a 16 year-old adolescent with schizophrenia.

BACKGROUND: Aripiprazole long-acting injection (LAI) is approved for the treatment of schizophrenia in adults. Recently, Europe and Canada approved the use of the two-injection start regimen: two separate injections of 400-mg long-acting aripiprazole along with a single 20-mg dose of oral aripiprazole. Aripiprazole showed efficacy in the treatment of adolescents with acute schizophrenia in several controlled trials, leading to its approval for 13- to 17-year-old adolescents with schizophrenia by the EMA. However, the LAI formulation still remains off-label in adolescents. CASE PRESENTATION: The patient was admitted to the General Psychiatry inpatient unit with a Positive and Negative Syndrome Scale (PANSS) total score of 136 and the Clinical Global Impression (CGI) score of 7. Aripiprazole was started and up-titrated to 30 mg/d. After 3 weeks, the positive symptoms were significantly reduced; however, he still showed prominent negative symptoms. Clozapine 100 mg/d was added, and in the following 2 weeks, the patient appeared slightly more communicative and generally more aware of himself and the others. The PANSS total score decreased to 81. Due to poor insight, the patient was at-risk not to take medications upon returning home; therefore, aripiprazole LAI was proposed. Since he urged to be discharged from the hospital, we opted for the two-injection start. The medication was optimally tolerated, with no evidence of akathisia or other side effects. One month later, global functioning and illness insight improved; Positive and Negative Syndrome Scale score was 43 and CGI score 2. CONCLUSIONS: Aripiprazole LAI showed good efficacy and tolerability in an adolescent with schizophrenia. The two-injection start regimen was a safe and effective option.

C-Reactive Protein as a Biomarker for Major Depressive Disorder?

The etiopathogenesis of depression is not entirely understood. Several studies have investigated the role of inflammation in major depressive disorder. The present work aims to review the literature on the association between C-Reactive Protein (CRP) and depression. A systematic review was performed for the topics of 'CRP' and 'depression' using the PubMed database from inception to December 2021. Fifty-six studies were identified and included in the review. Evidence suggested the presence of dysregulation in the inflammation system in individuals with depression. In most studies, higher blood CRP levels were associated with greater symptom severity, a specific pattern of depressive symptoms, and a worse response to treatment. Moreover, about one-third of depressed patients showed a low-grade inflammatory state, suggesting the presence of a different major depressive disorder (MDD) subgroup with a distinct etiopathogenesis, clinical course, treatment response, and prognosis, which could benefit from monitoring of CRP levels and might potentially respond to anti-inflammatory treatments. This work provides robust evidence about the potential role of CRP and its blood levels in depressive disorders. These findings can be relevant to developing new therapeutic strategies and better understanding if CRP may be considered a valuable biomarker for depression.

Number of episodes and duration of illness associated with hypertension and 10-year cardiovascular risk in patients with bipolar disorder type I.

Severe Mental Illnesses, including bipolar disorder (BD) and schizophrenia (SCZ), are burdened with an increased mortality and a significantly reduced life expectancy than general population, and cardiovascular diseases (CVD) are considered the most contributing conditions. The aim of the present study is to evaluate 10-year CV risk and the associated clinical characteristics in patients with SCZ, BD type I and II. Patients were consecutively recruited from two Italian psychiatric acute units. Single CV risk factors were assessed, and 10-year CV risk calculated by means of the CUORE Project 10-year CV risk algorithm, based on the combination of the following risk factors: age, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking habit, and hypertensive treatment. Three hundred patients were included. Patients with BD type I showed a higher prevalence of hypertension and 10-year CV risk score compared to the other groups. In subjects with BD type I, we found a significant correlation between duration of illness and number of mood episodes and both hypertension and 10-year CV risk score. Several preventive strategies should be provided to these vulnerable populations, such as correcting unhealthy lifestyles, prescribing medications at lower CV and metabolic risk, enhancing access to care.

Use of State Sequence Analysis in Pharmacoepidemiology: A Tutorial.

While state sequence analysis (SSA) has been long used in social sciences, its use in pharmacoepidemiology is still in its infancy. Indeed, this technique is relatively easy to use, and its intrinsic visual nature may help investigators to untangle the latent information within prescription data, facilitating the individuation of specific patterns and possible inappropriate use of medications. In this paper, we provide an educational primer of the most important learning concepts and methods of SSA, including measurement of dissimilarities between sequences, the application of clustering methods to identify sequence patterns, the use of complexity measures for sequence patterns, the graphical visualization of sequences, and the use of SSA in predictive models. As a worked example, we present an application of SSA to opioid prescription patterns in patients with non-cancer pain, using real-world data from Italy. We show how SSA allows the identification of patterns in prescriptions in these data that might not be evident using standard statistical approaches and how these patterns are associated with future discontinuation of opioid therapy.

A Systematic Review on TeleMental Health in Youth Mental Health: Focus on Anxiety, Depression and Obsessive-Compulsive Disorder.

Background and Objectives: The Internet is widely used and disseminated amongst youngsters and many web-based applications may serve to improve mental health care access, particularly in remote and distant sites or in settings where there is a shortage of mental health practitioners. However, in recent years, specific digital psychiatry interventions have been developed and implemented for special populations such as children and adolescents. Materials and Methods: Hereby, we describe the current state-of-the-art in the field of TMH application for young mental health, focusing on recent studies concerning anxiety, obsessive-compulsive disorder and affective disorders. Results: After screening and selection process, a total of 56 studies focusing on TMH applied to youth depression (n = 29), to only youth anxiety (n = 12) or mixed youth anxiety/depression (n = 7) and youth OCD (n = 8) were selected and retrieved. Conclusions: Telemental Health (TMH; i.e., the use of telecommunications and information technology to provide access to mental health assessment, diagnosis, intervention, consultation, supervision across distance) may offer an effective and efficacious tool to overcome many of the barriers encountering in the delivery of young mental health care.

ADHD and Bipolar Disorder in Adulthood: Clinical and Treatment Implications.

Attention deficit hyperactivity disorder (ADHD) is a condition that usually has its onset in childhood. Although the disorder persists into adulthood in half of cases, adult ADHD is often not recognized due to different psychopathological characteristics, quite often overlapping with other diagnoses such as mood, anxiety and personality disorders. This is especially true for bipolar disorder (BD), which shares several symptoms with adult ADHD. Moreover, besides an overlapping clinical presentation, BD is often co-occurring in adults with ADHD, with comorbidity figures as high as 20%. This review will focus on the comorbidity between ADHD and BD by exploring the magnitude of the phenomenon and evaluating the clinical and functional characteristics associated with ADHD-BD comorbidity in adults. Finally, the review will address the implications of pharmacologically treating the ADHD-BD comorbidity, providing suggestions in how to treat these complex patients and addressing the issue of treatment-induced manic switch with the use of stimulants and other medications for ADHD.

Severe and persistent mental illness (SPMI) in pregnancy and breastfeeding: focus on second-generation long acting injectable antipsychotics.

Introduction: Pregnant women and fetuses are more likely than ever to be exposed to antipsychotic drugs (APs) during pregnancy and postpartum period. Second-generation APs (SGA) are increasingly used among women in reproductive age. Key outcomes (i.e., congenital malformations, pregnancy and maternal outcomes, neonatal/infant risks, and developmental/long-term outcomes) following the exposure to APs remain limited in number and size and yield of inconsistent findings overall, particularly regarding long-acting injectable AP (LAI-APs) formulations.Areas covered: The review aims at providing a summary of current knowledge on potential risks and safety profile of LAI-APs during pregnancy and breastfeeding, specifically focusing on SGA.Expert opinion: The management of safety and tolerability of long-acting injectable AP (LAI-APs) is far from having solid scientific evidence. In fact, due to ethical reasons, there is a lack of randomized clinical trials that limits the reliability and generalizability of the available data on LAI-APs safety profile during the perinatal period, being limited in the scientific literature only to isolated case reports. Therefore, it seems to be important for the future pathways to perinatal mental health care, providing a network of specialized clinicians and systematically collecting data of pregnant/puerperal women on oral and/or LAI APs-therapy about mother and infant outcomes.

Peripheral BDNF levels in psychiatric patients with and without a history of suicide attempt: A systematic review and meta-analysis.

OBJECTIVE: Psychiatric patients are at increased risk of attempting suicide. Several potential biomarkers of suicide risk have been proposed with inconsistent findings. The present paper aimed to evaluate differences in peripheral BDNF levels between psychiatric patients with and without a history of suicide attempts. METHODS: We conducted a systematic review and meta-analysis following the PRISMA guidelines. Relevant papers published up to January 5, 2021 were identified searching the electronic databases Web of KnowledgeSM and PsycINFO. A random-effect meta-analysis was conducted using Stata 16. RESULTS: Thirteen studies met inclusion criteria. Overall, no significant differences in BDNF levels between the two groups were found (13 studies, n = 1340, Hedge's g = -0.21, 95% CI -0.44 to 0.02). Heterogeneity was substantial (I2 = 72.91%). Subgroup analyses revealed that BDNF levels were significantly reduced in plasma with medium effect size (5 studies, n = 363, Hedge's g = -0.44, 95% CI -0.86 to -0.02), but not in serum (8 studies, n = 977, Hedge's g = -0.09, 95% CI -0.33 to 0.15). No significant differences were found according to the type of diagnosis (major depressive disorder vs. other diagnoses) or the period of suicide attempt (lifetime vs. recent). CONCLUSION: The utility of BDNF as a biomarker of suicide attempts in psychiatric patients appears limited to its plasma concentration. Although caution interpretation is needed, our findings may represent a starting point for the design of rigorous case-control studies exploring the association between neurotrophins and suicidal behaviors.

Long-acting second-generation and oral antipsychotics for substance use disorders and psychotic symptoms: Prescribing attitudes among Italian psychiatrists.

PURPOSE: To explore Italian psychiatrists' attitudes toward the off-label use of second generation antipsychotics (SGAs) in patients with substance use disorder and psychotic symptoms. DESIGN AND METHODS: A sample of 300 Italian psychiatrists associated with the Italian Society of Neuropsychopharmacology was randomly selected to complete a survey about the off-label prescription of SGAs. FINDINGS: Oral aripiprazole (32.7%), olanzapine (30.2%), and quetiapine (25.2%) were considered "appropriate." Long-acting antipsychoticss were generally considered "inappropriate." PRACTICE IMPLICATIONS: Our findings reflect a substantial level of uncertainty and a lack of coherent clinical guidance within the realm of dual diagnosis treatment. Therefore, they emphasize the need to develop specific guidelines to improve the management of pharmacotherapy among this population.

Manic-Depressive Cycles in Bipolar Disorder: Clinical and Treatment Implications.

INTRODUCTION: Cycle patterns of bipolar disorders (BDs) have been previously shown to be associated with clinical characteristics and response to lithium salts. Here, we evaluated the distribution of different types of manic-depressive cycles in a large sample of patients with BD. The associations between a mania-depression-interval (MDI) course and depression-mania-interval (DMI) course with sociodemographic/clinical factors were also assessed in order to define specific clinical profiles. METHODS: In this cross-sectional study, 806 patients with BD admitted to the Psychiatric Unit of San Luigi Gonzaga Hospital in Orbassano and Molinette Hospital in Turin, Italy, were recruited. Patients were grouped according to the following course patterns: MDI, DMI, continuous cycling (CC, <4 episodes/year without intervals), rapid cycling (RC, ≥4 episodes/year), and irregular (IRR) cycling. We compared several sociodemographic and clinical variables in an MDI versus DMI course by means of ANOVA and Pearson χ2 with Bonferroni correction. RESULTS: Bipolar cycles were distributed as follows: 50.2% IRR course, 31.5% MDI course, 16% DMI course, 1.2% CC, and 1% RC. Compared to DMI course, patients with an MDI course were more often men, younger, with an earlier onset, a manic polarity onset, and more lifetime compulsory admissions. They were more frequently treated with lithium and antipsychotics. Patients with a DMI course had older age at diagnosis and at first mood-stabilizer treatment and were more often misdiagnosed with a major depressive disorder. These patients were more commonly treated with anticonvulsants, and they had more frequently failed treatment trials with lithium salts in the past. CONCLUSION: This study supports the utility of classifying BD according to their course patterns. This classification holds prognostic as well as therapeutic implications.