Comparison of Typical and Atypical Long-Acting Antipsychotics in a Real-World Sample in terms of Treatment Adherence and Factors Influencing Treatment Choice: A One-Year Follow-Up Study.

Real-world outcomes and practice patterns among patients with schizophrenia when switched from oral antipsychotics to long-acting injectable formulations after hospitalization.

This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015–December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18–34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = −0.19, −0.26 and −0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = −0.20, −0.24, −0.21, respectively) and ED admissions (SMD = −0.15, −0.13, −0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated.

To quantify and explain variation in use of long-acting injectable antipsychotics (LAIs) in the United States, and understand the relationship between patient characteristics, drug reimbursement policies, and LAI prescribing after relapse. A cohort of recently relapsed patients with schizophrenia ages 18 to 64, were identified immediately after discharge from a related inpatient hospitalization, partial hospitalization, or emergency room visit, drawn from 2004 to 2006 Medicaid claims, and followed for 90days until LAI initiation. Data on state-level Medicaid prior authorization (PA) policies for LAIs were collected. Sequential longitudinal Poisson regression models were developed to understand the relationship between patient and PA policy variables and LAI prescribing, including prior adherence to oral antipsychotics, demographics, clinical variables, and presence of PA policy for LAI. Among 36282 patients, 3.1% received risperidone LAI, and 3.8% received a first-generation (FGA) LAI with wide variation across states. Prior adherence ranged from 29% to 89% but was marginally associated with initiation and did not explain variation for LAI prescribing. FGA initiation was associated with geography and race/ethnicity but not PA policy. For risperidone LAI initiation, demographics and clinical factors explained, respectively, 5.0% and 3.0% of the variation; PA policy had a large negative association with initiation (RR=0.41; 95%CI 0.20-0.87) and explained 8.4% of the variation. PA policies may represent a major treatment barrier for risperidone LAI among relapsed patients. Non-adherence plays a little role in predicting which patients receive LAIs. Policy makers and health insurers will need to consider these findings when guiding the use of LAIs. KEY POINTS Among a nationwide cohort of relapsed schizophrenia patients enrolled in US Medicaid, 3.1% received Risperdal Consta, a long-acting injectable antipsychotic (LAI), and 3.8% initiated a first-generation first-generation LAI within 90days after discharge. During 2004 to 2006, there was marked variation in 90day post-relapse initiation of Risperdal-Consta-a newly marketed medication during this period-and also marked variation in 90day post-relapse initiation of any first-generation LAI, which appeared to be associated with race/ethnicity and geography. Prior authorization policies were associated with substantially lower initiation of Risperdal Consta in this cohort of relapsed patients even after accounting for clinical indication (non-adherence), relapse history, demographics, adjunctive medication, and mental health service use.

Disease relapse, all-cause mortality, and adverse events associated with long-acting injectable antipsychotics versus oral antipsychotics in older people with schizophrenia in Hong Kong: a population-based within-subject analysis.

A Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics on Time to Rehospitalization Within 1 Year of Discharge in Elderly Patients With Schizophrenia

The present cross-sectional, retrospective study aimed to assess the prevalence of cardiovascular disease (CVD) risk factors and metabolic syndrome in a sample of psychiatric patients treated with long-acting injectable antipsychotics (LAIs). The clinical charts of 120 patients, mainly diagnosed with schizophrenia (30.0%), schizoaffective disorder (15.0%), and bipolar disorder (13.3%) on LAIs therapy - initiated in the period from 2013 to 2019 and lasting at least one year - were retrospectively reviewed and related socio-demographic, clinical and laboratory variables were collected. The 70.8% of patients were treated with first-generation LAIs, and the remaining 29.2% with second-generation LAIs. The overall sample showed low compliance in performing the required exams and evaluations related to CVD risk factors. The prevalence of metabolic syndrome was 30.8%, and, considering specific CVD risk factors, 55% of the total sample reported abdominal obesity, 43.3% arterial hypertension, 41.7% low HDL-cholesterol, 25.8% hypertriglyceridemia, and 20.8% fasting hyperglycemia. Lastly, 6.7% showed prolonged corrected QT (QTc) interval at the ECG. Patients treated with LAIs should be regularly monitored for metabolic changes and CVD risk factors. Metabolic changes rapidly develop after initiating an antipsychotic therapy and these often involve parameters, that can be easily recorded in an outpatient setting (e.g. abdominal obesity and hypertension).

ABSTRACTIntroduction: Many patients with schizophrenia exhibit difficulties in maintaining adherence to oral antipsychotics, calling for more reliable drug delivery systems.Areas covered: While non-randomized studies have indicated consistent effectiveness of long-acting injectable antipsychotics (LAIs) over oral counterparts to prevent negative consequences such as relapse, hospitalization and all-cause discontinuation, efficacy results from randomized controlled comparative trials have not been that impressive. The results rely heavily on the study design and the population studied. Further, LAIs are frequently used as an adjunctive to ongoing other antipsychotics or psychotropics, but not solely, in the real world.Expert opinion: To put LAI–oral comparisons into clinical context, the following information is urgently necessary: (1) How LAIs compare with each other in head-to-head comparisons? (2) How effective is it to switch among different LAIs? (3) How early in the treatment stage should LAIs be utilized? (4) How long the interval of LAI administration can be extended? (5) How LAIs compare with clozapine in head-to-head comparisons? (6) How effective are LAIs when clozapine is ineffective? (7) How effective is clozapine when LAIs are ineffective? (8) How effective is it to combine clozapine and LAIs when neither is effective alone? This paper narratively discusses these critical perspectives.

Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy. Long-acting injectable (LAI) antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders, but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy. To summarize relevant data on maternal, pregnancy, neonatal, and developmental outcomes from published cases of LAI antipsychotic use in pregnancy. A literature search was performed through November 11, 2023, using three online databases: PubMed/MEDLINE, Scopus, and Web of Science. Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy, with available full texts, were included. Descriptive statistics, narrative summation, and tabulation of the extracted data were performed. A total of 19 publications satisfied the inclusion criteria: 3 case series, 15 case reports, and 1 conference abstract. They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies. The use of second-generation LAI antipsychotics was reported in the majority (n = 47; 61.0%) of pregnancies. First-generation LAI antipsychotics were administered during 30 pregnancies (39.0%). Most of the women (approximately 64%) had either satisfactory control of symptoms or no information about relapse, while approximately 12% of them had developed gestational diabetes mellitus. A minority of cases reported adverse outcomes such as stillbirth, spontaneous abortion, preterm birth, low birth weight, congenital anomalies, and neurological manifestations in newborns. However, there were no reports of negative long-term developmental outcomes. Currently available data seem reassuring, but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

How Would You Like to Take Your Medicine 2 Times a Year? Paliperidone Palmitate Every 6 Months for the Maintenance Treatment of Schizophrenia

Long-acting injectable antipsychotics (LAIAs) are an efficacious and well-tolerated treatment in adults with schizophrenia spectrum disorders (SSD). However, there is less evidence for their use in children and adolescents. The aim of this systematic review was to summarize findings regarding the effectiveness and side effects of LAIA in children and adolescents with SSD. Four databases (Web of Science, PubMed, MEDES, and Dialnet) were systematically searched for articles published between inception and 12 March, 2022, with the following inclusion criteria: (1) original articles or case reports; (2) providing data on efficacy/effectiveness or safety/tolerability of LAIA treatment in children and adolescents diagnosed with SSD (schizophrenia, schizoaffective disorder, schizophreniform disorder, non-affective psychotic disorder); (3) mean age of samples ≤ 18 years; and (4) written in English or Spanish. Exclusion criteria were review articles, clinical guides, expert consensus as well as posters or oral communication in conferences. The risk of bias was assessed using the ROBIS tool. From 847 articles found, 13 met the inclusion criteria. These included seven single case reports or case series, four retrospective chart reviews, a 24-week open-label trial, and one observational prospective study, covering a total of 119 adolescents (aged 12-17 years) with SSD. Almost all the articles described data on second-generation LAIA (53 patients on risperidone [once every other week], 33 on paliperidone palmitate [once monthly], 10 on aripiprazole [once monthly], and two on olanzapine pamoate [once monthly]). Twenty-one patients were reported to be only on first-generation LAIAs. Non-adherence was the main reason for starting an LAIA. In all of the studies, the use of LAIAs was associated with improvement in the patients' symptoms. There are few studies assessing the use of LAIAs in adolescents with SSD. Overall, these treatments have suggested good effectiveness and acceptable safety and tolerability. However, we found no studies examining their use in children aged < 12 years. The problems and benefits linked to this type of antipsychotic formulation in the child and adolescent population require further study, ideally with prospective, controlled designs.

Background and importanceTreatment with long acting injectable (LAI) antipsychotics has been shown to improve treatment adherence compared with oral antipsychotics, but it is still controversial if adherence is modified with...

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment.

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.

Daily oral antipsychotics (OAPs) are the mainstay of schizophrenia treatment; however, long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and improved outcomes. This study assessed the real-world comparative effectiveness of LAIs and daily OAPs using claims data from a nationally representative sample of fee-for-service Medicare beneficiaries with schizophrenia. Antipsychotic discontinuation, psychiatric hospitalization, and treatment failure were compared relative to different reference groups using within-individual Cox regression models. The study included 152,835 patients (mean age, 53.5years; 54.0% male and 61.5% white). LAIs when grouped by dosing intervals were associated with significantly lower risk of antipsychotic discontinuation (hazard ratios [HRs] 0.27-0.69), psychiatric hospitalization (HRs 0.76-0.88), and treatment failure (HRs 0.55-0.74) compared with OAPs. When LAIs of different dosing intervals and OAPs were broken out by type of agent and compared with oral risperidone, second-generation LAIs, specifically LAI paliperidone (every 3months [Q3M] and monthly [Q1M]), LAI aripiprazole (Q1M), and LAI risperidone (primarily every 2weeks), had a significantly lower risk of antipsychotic discontinuation (HRs 0.19-0.67), psychiatric hospitalization (HRs 0.76-0.91), and treatment failure (HRs 0.53-0.85). Second-generation LAI paliperidone (Q3M) had the lowest risk for negative outcomes relative to OAPs; this effect was maintained when the reference group was changed to oral risperidone, LAI risperidone, LAI aripiprazole (Q1M), and LAI haloperidol (Q1M) (33-47% lower risk). Efforts are needed to enhance identification of appropriate candidates for LAIs and increase their uptake, especially longer dosing interval LAIs, in the Medicare population.

Prescription patterns in patients with schizophrenia who discontinued long-acting injectable antipsychotics: A chart-review.