Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

Adult ADHD: a study on evaluation and treatment pathways in Italian Mental Health Services. A black hole in the National System and the European Health System

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

Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

BACKGROUND: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses.OBJECTIVE: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors.METHODS: The STAR Network 'Depot Study' was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively.RESULTS: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4-44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3-43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4-84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6-40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6-27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742-0.981; p=0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003-4.634; p=0.049).CONCLUSIONS: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation

Reasons for initiating long-acting antipsychotics in psychiatric practice: findings from the STAR Network Depot Study

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient\u2019s attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient\u2019s engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies

Postpartum depression screening in mothers and fathers at well-child visits: a feasibility study within the NASCITA cohort

Objective To assess the feasibility of the family paediatrician’s (FP) role in identifying the signs of postpartum depression in parents in time to guarantee child well-being.Design, setting and participants Data for this observational prospective study were collected within the NASCITA (NAscere e creSCere in ITAlia) cohort. During the first visit, paediatricians collected sociodemographic data regarding the parents and information about their health status, the pregnancy and the delivery. Whooley questions were administered during the first and second visits (scheduled 60–90 days after childbirth). Moreover, on the third visit (5–7 months after childbirth) the FP was asked to answer ‘yes’ or ‘no’ to a question on the parental postpartum depression, based on his knowledge and on the acquired information.Results In 2203 couples who completed the assessment, 529 mothers (19.9%), 141 fathers (6.3%) and 110 (5%) couples reported any depressive symptomatology. Of these, 141 mothers (5.3% of the total sample) and 18 fathers (0.8% of the total sample) were classified as ‘likely depressed’. An association was found between maternal postnatal depressive symptoms and having a diagnosed psychiatric disorder during pregnancy (OR 9.49, 95% CI: 3.20 to 28.17), not exclusively breastfeeding at hospital discharge (OR 1.76, 95% CI: 1.19 to 2.61) and the presence of child sleeping disorders at 3 (OR 2.46, 95% CI: 1.41 to 4.28) and 6 months (OR 2.18, 95% CI: 1.37 to 3.47). Another significant predictor of postpartum depression was being primiparous (OR 1.99, 95% CI: 1.31 to 3.02). Concerning the fathers, a significant association was reported only between likely depressed fathers and child sleeping disorders at 3 months (OR 7.64, 95% CI: 2.92 to 19.97). Moreover, having a likely depressed partner was strongly associated with depressive symptoms in fathers (OR 85.53, 95% CI 26.83 to 272.69).Conclusions The findings of this study support the feasibility of an active screening programme for parental postnatal depression during well-child visits as an integral part of postpartum care.Trial registration number NCT03894566; Pre-results

National, longitudinal NASCITA birth cohort study: prevalence of overweight at 12 months of age in children born healthy

Objective To estimate the prevalence of overweight at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight.Methods The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (<5th), normal weight (5–84th) and overweight (≥85th centile) at 12 months of age according to the WHO percentiles of body mass index (BMI) and the prevalence of overweight was estimated. To test the association between the chance of being overweight and parental and newborn characteristics, and infant feeding, healthy newborns (no preterm/low birth weight and with no malformations), with appropriate-for-gestational-age birth weight were selected, and univariate and multivariate analyses were performed.Results The prevalence of overweight was 23.5% (95% CI 22.2% to 24.8%) in all cohort members with 12-month data (N=4270), and 23.1% in the appropriate-for-gestational age subsample (N=2835).A big infant appetite (OR 3.92, 95% CI 2.40 to 6.40) and living in southern Italy (OR 1.58, 95% CI 1.29 to 1.94) were the main variables associated with a greater likelihood of being overweight. Breastfeeding practice did not influence the chance of being overweight, but was associated with an increase (exclusive breast feeding for at least 6 months) or a decrease (breast feeding for at least 12 months) in BMI z score at 12 months.Conclusions The sociodemographic factors (eg, area of residence, maternal employment status) seem to be the most relevant determinants influencing the chance of being overweight at 12 months. Early interventions, with particular attention to vulnerable families, may be helpful in preventing childhood and adult obesity

Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy.Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network \u201cDepot\u201d Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs

Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network \u201cDepot\u201d Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs