Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia.

PURPOSE/BACKGROUND: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. METHODS/PROCEDURES: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. FINDINGS/RESULTS: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. IMPLICATIONS/CONCLUSIONS: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

Treatment persistence with aripiprazole once monthly: a 4-year follow-up.

OBJECTIVES: Treatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months. METHODS: This was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication. RESULTS: Study subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit. The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM. Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162-0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician's choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues. CONCLUSIONS: In subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations.

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study.

PURPOSE: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. METHODS: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. RESULTS: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends' relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. CONCLUSIONS: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. LEVEL OF EVIDENCE IV: Evidence obtained from multiple time series analysis such as case studies.

Pathways to specialist care for eating disorders: An Italian multicentre study.

Two hundred forty six patients with eating disorders (EDs) recruited from eight Italian specialized treatment centres were administered with the World Health Organization "Encounter Form," a standardized schedule that makes it possible to characterize the clinical pathways that patients follow to reach specialized care. The median time from symptoms onset to specialized care was 114 weeks. Primary "points of access to care" were general practitioners (25%), psychiatrists (18%), and clinical nutritionists (17%), followed by various other carers. All patients received specific psychotherapy, whereas only 11% of them were given psychotropic drugs. EDs are characterized by complex care pathways, with low rates of direct access to specialized care. Although the role of general practitioners remains crucial, they tend to follow different clinical routes to refer ED patients. Educational programmes on EDs should be addressed to general practitioners and clinical nutritionists, in order to ease the transition of ED patients to a mental health care setting.

The Role of Lurasidone in Managing Depressive Symptoms in People with Schizophrenia: A Review.

BACKGROUND: Schizophrenia is a severe mental disorder characterized by positive, negative, affective, and cognitive symptoms. Affective symptoms in patients with schizophrenia have traditionally been overlooked or even neglected because they are not considered as fundamental as positive and negative symptoms in the choice of medication. METHODS: This paper aims to systematically evaluate the efficacy and safety of lurasidone in the treatment of depressive symptoms of schizophrenia. RESULTS: Lurasidone appears to be particularly effective on the depressive symptomatology of schizophrenia while also alleviating the positive and negative symptoms associated with the illness. CONCLUSIONS: The efficacy of lurasidone in treating patients with first-episode psychosis who present with predominant depressive symptoms suggests that this medication may be a valuable treatment option not only for established cases of schizophrenia but also for individuals in the early stages of the illness. The good tolerability of lurasidone is an important factor that may positively influence treatment decisions.

A Feasible Methodological Approach to Estimate the Burden of Autism Spectrum Disorder: Results from the EPI-ASD Study in the Province of Lecce (Southern Italy).

Diagnoses of Autism Spectrum Disorder (ASD) have rapidly increased globally. However, the lack of comprehensive epidemiological surveys and surveillance systems, able to provide official data at a national or European level is one of the main issues in the monitoring of this condition. The present study aimed to estimate the prevalence of ASD in children and adolescents aged 3-18 years old living in the province of Lecce (Southern Italy) through official data provided by the Local Health Authority of Lecce (ASL/LE) up to 31 October 2020, and compare it with school-based data concerning the number of students needing support for ASD. Based on data provided by the ASL/LE, in 2020 there were 509 cases of ASD among children and adolescents aged 3-18 years old, corresponding to a prevalence of 0.46%. A total of 408 (80.2%) were boys and 101 (19.8%) were girls. In relation to their age, 155 ASD cases (0.90%) were diagnosed in the 3-5 age group, while 222 (0.55%) in the 6-11 age group and 132 (0.25%) in the 12-18 age group. Prevalence of ASD assessed by school-based dataset was underestimated in the 3-5 age group, while the 6-11 and 12-18 age groups were consistent with the official data provided by the ASL/LE.

The impact of COVID-19 lockdown and of the following "re-opening" period on specific and general psychopathology in people with Eating Disorders: the emergent role of internalizing symptoms.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on specific Eating Disorder (ED) and general psychopathology in people with an ED diagnosis during the lockdown period and after the end of the related containment measures. METHODS: People with clinically defined diagnosis and undergoing treatment for an ED completed an online survey, which included adapted questions from standardized psychometric scales. Data relative to three different time periods (before, during and after the end of lockdown) were collected. Psychopathological changes over these periods were investigated and compared through one-way analysis of variance or covariance with repeated measures. RESULTS: Three hundred twelve people completed the survey (57.4% diagnosed with Anorexia Nervosa (AN) or atypical AN, 20.2% with Bulimia Nervosa, 15.4% with Binge Eating Disorder, 7.05% with Other Specified Feeding or Eating Disorders). The severity of both specific and general psychopathology increased during the lockdown and the rise of general symptoms persisted in the following re-opening phase, except for suicide ideation. Almost all of these findings were not affected by ED diagnosis, participants' age and illness duration. LIMITATIONS: The retrospective nature of data collection is the main limitation of the study. CONCLUSIONS: People with EDs showed a COVID-19 emergency-induced worsening of both general and specific psychopathology. The effect on general psychopathology persisted in the re-opening period. These findings suggest a high stress vulnerability of ED individuals with important effects on internalizing symptoms, which are worth of attention by clinicians.

Early Screening of the Autism Spectrum Disorders: Validity Properties and Cross-Cultural Generalizability of the First Year Inventory in Italy.

This study examined the cross-cultural generalisability of the First Year Inventory (FYI) on an Italian sample, testing its construct validity, consistency, and structural validity. Six hundred ninety-eight parents of children aged 11-13 months completed the questionnaire. Similarities between analyses of Italian and American/Israeli samples were found, as were demonstrations of the instrument's construct validity and internal consistency with both groups. The original factorial structure was not demonstrated; thus, a new factorial structure was tested, and a short version of the FYI was demonstrated via confirmatory factor analysis. The findings supported the generalisability of the Italian version of the FYI and its validity. The FYI may aid in medical decision-making on further steps for referral of the child to an early diagnostic assessment.

Assessment and Management of Cognitive and Psychosocial Dysfunctions in Patients With Major Depressive Disorder: A Clinical Review.

Background: Full functional recovery is defined as a state in which patients are again able to enjoy their usual activities, return to work, and take care of themselves, and it should represent the end goal of treatment in patients with major depressive disorder (MDD). Patients with MDD report many unmet needs, including residual cognitive symptoms, lack of improvement in psychosocial functioning and life satisfaction, even during mood symptom remission. In this paper, we aim to: (a) identify the available assessment tools for evaluating cognitive and psychosocial functioning in patients with MDD; (b) provide an overview of therapeutic options that can improve full functional recovery in MDD also by improving cognitive symptoms. Methods: The relevant databases MEDLINE, ISI Web of Knowledge - Web of Science Index, Cochrane Reviews Library and PsychoINFO were searched for identifying papers on validated tools for the assessment of cognitive and personal functioning in patients with MDD. Results: New assessment tools (such as the THINC-it TOOL, the COBRA, the SCIP-D, and the UPSA-D) have been developed for evaluating the cognitive dysfunction in MDD patients. Adopting these tools in the clinical routine practice is useful to evaluate the improvement in cognitive functioning and, therefore, the achievement of full functioning recovery. The optimal management of patients with MDD include the combination of pharmacological compounds and psychosocial interventions for achieving full functional recovery in patients with MDD. Conclusions: Full functional recovery must be the target of any treatment programme for patients with MDD. In order to achieve this goal, it is necessary to develop personalized treatment and integrate psychosocial and psychopharmacological interventions.

Clinical trial methodology to assess the efficacy/effectiveness of long-acting antipsychotics: Randomized controlled trials vs naturalistic studies.

Schizophrenia presents unique difficulties in clinical trial design associated with the condition's variable presentation and clinical course, and multiple features influencing affect, cognition, volition and perception. Randomized controlled trials (RCTs) are explanatory studies using a carefully selected patient population, predefined assessment intervals and, generally, symptom-focused endpoints. Naturalistic studies are pragmatic, with no active intervention, and outcomes that are generally those used in clinical practice (e.g. hospitalization, relapse rate). Both naturalistic studies and RCTs have pros and cons, making it difficult for physicians in clinical practice to apply research findings to their own treatment decisions. The choice of clinical trial design can have a significant impact on the comparative effectiveness or efficacy of drugs. This is particularly true for studies comparing long-acting injectable (LAI) antipsychotics with oral antipsychotics in schizophrenia, in which RCTs generally show no benefit for LAIs over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAIs versus oral therapy. This article reviews the pros and cons of different study types, using published examples. Criteria are outlined to help physicians design appropriate prospective studies in schizophrenia including the relevant pragmatic and/or explanatory features, as required.

Rethinking the role of long-acting atypical antipsychotics in the community setting.

Schizophrenia is a relapsing and evolving condition, which requires treatment continuity. Increasing evidence shows that antipsychotic discontinuation is associated with relapse in most patients, and that early interventions have a positive impact on long-term outcomes. Poor adherence to antipsychotics is a major factor in the treatment of schizophrenia and a relevant risk factor for relapse. Considerable effort has been made toward improving adherence, including the development of long-acting injectable (LAI) antipsychotics. LAIs have traditionally been reserved for patients with repeated nonadherence; currently, several misconceptions prevent their more widespread use. The recent introduction of LAI formulations of atypical antipsychotics and the encouraging results in terms of the reduction in relapse rates and avoidance of hospitalization warrant a reassessment of the role of LAIs in the management of schizophrenia. This paper presents the position of a panel of nine Italian schizophrenia experts on the use of novel LAI medications, with a focus on community-based services, the prevailing setting of schizophrenia treatment in Italy. The need to change the attitude toward LAIs--no longer a treatment of last resort, but a component of multimodal strategies leading patients to remission and rehabilitation--is emphasized. The paper also presents recommendations for LAI atypical antipsychotic use in the community setting.