Second-generation Long-acting Injectable Antipsychotics Research Articles

Outcomes of long-acting injectable antipsychotics use in pregnancy: A literature review.

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.

Long-Acting Injectable Second-Generation Antipsychotics in Seriously Ill Patients with Schizophrenia: Doses, Plasma Levels, and Treatment Outcomes.

This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into "standard PL" and "high PL" (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose-PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.

Impact of long-acting injectable antipsychotics vs. oral medication on relapses of patients with psychosis and bipolar disorder

Relapse associated with multiple hospital readmissions of patients with chronic and severe mental disorders, such as psychosis and bipolar disorder, is frequently associated with non-adherence to treatment. The primary aim of the study was to compare the effectiveness of long-acting injectable (LAI) treatment, vs. oral medication in reducing readmissions of patients with psychotic or bipolar disorder in a community sample of 164 patients with psychosis and 29 patients with bipolar disorder (n = 193), with poor adherence to oral medication. The mean follow up period was 5.6 years and the number of readmissions were compared for an equal-length period of oral treatment preceding the onset of LAI administration. We observed a significant decrease of 45.2 % in total hospital readmissions after receiving LAIs treatment. The effect was significant both for patients with a pre-LAI treatment history of predominantly voluntary hospitalizations and with predominantly involuntary admissions. In addition, we observed equal effectiveness of first- vs. second-generation LAIs in reducing total hospital readmissions regardless of type of pre-treatment admission history (voluntary vs. involuntary). LAIs appear to be effective in reducing both voluntary and involuntary hospital readmissions in patients with psychosis and bipolar disorder with a history of poor adherence to treatment.

Second Generation Long-Acting Injectable Antipsychotics in Schizophrenia: The Patient's Subjective Quality of Life, Well-Being, and Satisfaction.

Schizophrenia (SZ) is among the twenty most disabling diseases worldwide. Subjective quality of life, well-being, and satisfaction are core elements to achieving personal recovery from the disorder. Long-acting injectable second-generation antipsychotics (SGA-LAIs) represent a valid therapeutic option for the treatment of SZ as they guarantee good efficacy and adherence to treatment. The aim of this rapid review is to summarize the evidence on the efficacy of SGA-LAIs in improving subjective quality of life, well-being, and satisfaction. The PubMed database was searched for original studies using SGA, LAI, risperidone, paliperidone, aripiprazole, olanzapine, SZ, and psychosis as keywords. Twenty-one studies were included: 13 clinical trials, 7 observational studies, and 1 post hoc analysis. It has been shown that SGA-LAIs bring an improvement to specific domains of subjective and self-rated quality of life, well-being, or satisfaction in prospective observational studies without a control arm and in randomized controlled trials versus placebo. The superiority of SGA-LAIs as compared with oral equivalents and haloperidol-LAI has been reported by some randomized controlled and observational studies. Although promising, the evidence is still limited because of the lack of studies and several methodological issues concerning the choice of the sample, the evaluation of the outcome variables, and the study design. New methodologically sound studies are needed.

Comparison of health resource usage and costs associated with first-generation and second-generation long-acting injectable antipsychotics for patients with schizophrenia: A nationwide population-based cohort study.

The aim of this study was to examine psychiatric resource utilization, medical costs and clinical outcomes for patients with schizophrenia who received either first-generation or second-generation long-acting injectable (LAI) antipsychotics. A retrospective cohort study was conducted using data from Taiwan's National Health Insurance Research Database (NHIRD). Patients who began either first-generation or second-generation LAI treatment between 2015 and 2017 were enrolled and followed for three years. The data were evaluated using survival analysis and Cox proportional hazards regression models. Our findings demonstrated that both first- and second-generation LAI therapies led to notable reductions in the frequency of psychiatric hospitalizations and the duration of hospital stays when compared to the initial measurements. Additionally, the second-generation LAI group exhibited significantly lower rates of psychiatric emergencies and hospitalizations, as well as shorter hospital stays, compared to the first-generation LAI group. However, it is worth noting that the second-generation LAI group incurred higher pharmacy fees despite these favorable outcomes. The utilization of both first- and second-generation LAIs can enhance medication adherence and decrease the risk of acute exacerbation in patients with schizophrenia. These findings hold significant implications for schizophrenia management and the efficient allocation of healthcare resources.

Racial disparities in utilization of first-generation versus second-generation long-acting injectable antipsychotics in Medicaid beneficiaries with schizophrenia.

Multiple studies report racial disparities in antipsychotic prescription patterns. This study assessed demographic and clinical factors associated with the utilization of first-generation (FG) versus second-generation (SG) long-acting injectable (LAI) antipsychotics. This retrospective, observational cohort analysis used claims data from the IBM MarketScan® Multi-State Medicaid database. The study included adults with an LAI claim between 01-January-2009 and 31-December-2018, an ICD-9-CM or ICD-10-CM diagnosis of schizophrenia, race recorded as Black or White, and ≥12months of continuous enrollment before the index LAI. Descriptive analysis detailed the relationship between race and FG or SG LAI initiation. Multivariate logistic regression was used to assess potential associations with FG vs. SG LAI initiation, including clinical and demographic factors, comorbidities, and index year. A total of 10,773 patients were included: 6659 (62%) Black and 4114 (38%) White. Black patients had a higher utilization of FG LAIs than White patients (46.8% vs. 38.9%) over the 10years analyzed. Black patients were more likely to utilize FG LAIs than White patients (odds ratio: 1.47; 95% CI: 1.34, 1.62) after controlling for index year and covariates (race, age, gender, insurance plan type, Quan-Charlson Comorbidity index score, comorbidities, prior medications). Significant predictors of FG LAI utilization were older age, type of baseline oral antipsychotic (FG vs SG), type of coverage (managed care vs fee for service), and greater comorbidity burden. The utilization of FG LAIs was greater in Black compared to White Medicaid beneficiaries with schizophrenia over a 10-year period. These findings suggest that racial disparities exist in LAI initiation, with implications for differential quality of schizophrenia treatment.

Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay

Background Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. Methods Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015–12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. Results Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). Conclusions Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.

Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.

Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1. Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations. SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.

Response to comment on the recently published article "An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use".

Response to comment on the recently published article "An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use".

Comment on “An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use”

Comment on “An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use”

Use of Long-Acting Injectable Antipsychotics in a Clinical Sample of Community-Dwelling Patients with Schizophrenia-Spectrum Disorders in Rural Greece.

Data on the use of long-acting injectable antipsychotics (LAIs) in rural community mental healthcare settings are scarce. This study aimed to investigate the prescription patterns of LAIs in a clinical sample of patients with schizophrenia-spectrum disorders in rural Greece. All patients with schizophrenia-spectrum disorders who regularly attend the Mobile Mental Health Unit of the prefectures of Ioannina and Thesprotia (MMHU I-T) in northwestern Greece were included in the study. The sample consists of 87 patients (59 males and 28 females) with a mean age of 54.4 years and a mean illness duration of 28 years. Most patients (72.4%) received antipsychotic monotherapy, and nearly 30% received an LAI formulation, mostly a second-generation LAI (20 of 26 patients, 76.9%). The treatment regimen comprised benzodiazepines in one-third of the patients and antidepressants in one-quarter. There was no statistically significant association between treatment regimen and the clinical and demographic variables studied, except for biological sex (female). The percentage of patients treated with LAIs in this study was almost three times higher than the rate previously reported in Greece and is higher than the rates reported in other countries. Patients with schizophrenia-spectrum disorders in rural Greece may have adequate access to innovative treatment with second-generation LAIs. Further research is needed to demonstrate the cost-effectiveness of LAI treatment in rural communities and to elucidate the factors associated with such treatment.

Benzodiazepines and Mood Stabilizers in Schizophrenia Patients Treated with Oral versus Long-Acting Injectable Antipsychotics—An Observational Study

Schizophrenia is a chronic, invalidating, and polymorphic disease, characterized by relapses and remission periods. The main treatment option in schizophrenia are antipsychotics, administered as an oral or as a long-acting injectable (LAI) formulation. Although international guidelines rarely recommend it, mood stabilizers (MS) and/or benzodiazepines (BZD) are frequently prescribed as adjunctive therapy in schizophrenia patients for various reasons. This is an observational, cross-sectional study including stabilized schizophrenia patients. A total of 315 patients were enrolled. Of these, 77 patients (24.44%) were stabilized on LAIs and 238 (75.56%) patients on oral antipsychotics (OAP). Eighty-four patients (26.66%) had concomitant treatment with MS and 119 patients (37.77%) had concomitant benzodiazepine treatment. No statistical significance was observed in MS or BZD use between LAIs and OAPs. In total, 136 patients (43.17%) were stabilized on antipsychotic monotherapy. Our study shows that the long-term use of benzodiazepines and mood stabilizers remains elevated among stabilized schizophrenia patients, regardless of the antipsychotic formulation (oral or LAI). Patients receiving second-generation LAI antipsychotics (SGA-LAI) seem to be more likely to be stabilized on monotherapy compared to those receiving oral antipsychotics. Further randomized controlled trials are necessary in order to clarify the benefits of the current drug polypharmacy trends.

Factors influencing the prescription of first-generation versus second-generation long-acting injectable antipsychotics: findings from a sample of male prisoners

Factors influencing the prescription of first-generation versus second-generation long-acting injectable antipsychotics: findings from a sample of male prisoners

Effectiveness of oral versus long-acting injectable second-generation antipsychotics in suicide prevention among people with severe schizophrenia

Effectiveness of oral versus long-acting injectable second-generation antipsychotics in suicide prevention among people with severe schizophrenia

Cardiovascular risk factors and metabolic syndrome in patients treated with long-acting injectables antipsychotics: a retrospective study.

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).

An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use.

There are now 9 available FDA-approved second-generation long-acting injectable antipsychotics including aripiprazole (3), olanzapine (1), paliperidone (3), and risperidone (2). These high-cost medications are commonly used with the goal of improving adherence and patient outcomes. With almost 2 decades of use, key aspects have been well studied, including population pharmacokinetics, CYP interactions and various clinical and economic outcomes. However, there are still unknowns with these medications. Issues including adherence, transition from oral antipsychotics, renal dosing, pharmacogenomics, and managing missed doses will be addressed in the context of 4 patient cases.

Reasons for Antipsychotic Treatment Switch

Objective: Switching of antipsychotic medications, which are used for many psychiatric conditions, is common. However, reasons and clinical documentation of such switches have scarcely been studied.Methods: A systematic, retrospective review of prescription records and prescriber notes was conducted to characterize reasons for and types of antipsychotic switches at one hospital during inpatient or outpatient care, starting August 1, 2017, until 270 antipsychotic switches with type and reasons were collected, as required by power analysis.Results: After removing 7 cases in which quetiapine was switched to a non-antipsychotic agent, 263 antipsychotic switches involving 195 unique subjects (median age = 31 [interquartile range, 24-47] years; schizophrenia = 36.9%, bipolar disorder = 27.7%, schizoaffective disorder = 18.5%) were analyzed. Frequent reasons for antipsychotic switch were intolerability (45.7%) and inefficacy/clinical worsening (17.6%). Reasons did not differ by race (P = .2644), age (P = .0621), or insurance type (P = .2970), but differed heterogeneously regarding different reasons by sex (P = .004). The most common reported switches were from second-generation oral antipsychotics (SGA-OAPs) to other SGA-OAPs (N = 155, 58.9%), mostly due to tolerability or inefficacy; second-generation long-acting injectable antipsychotics (SGA-LAIs) to SGA-OAPs (11%), mostly due to intolerability, patient preference, or insurance coverage problems; and SGA-OAPs to SGA-LAIs (10.7%) due to nonadherence. Reasons for antipsychotic switch were properly documented in 208 (79.1%) of the prescriber notes.Conclusions: In this retrospective chart review, switching varied by sex regarding reasons and occurred almost in half of the cases due to intolerability. Different reasons predominated in switches from SGA-OAP to SGA-OAP, SGA-LAI to SGA-OAP, and SGA-OAP to SGA-LAI. One in 5 switches were not properly documented, requiring attention.

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study

BackgroundLong-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia.MethodsThis retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods.ResultsAmong 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p < 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 [SD $68,887] versus $74,131 [SD $75,941]), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 [SD $63,428] versus $68,403 [SD $72,088]) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status.ConclusionsSGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.

Bipolar bozukluk tip I hastalarının tedavisinde uzun etkili antipsikotiklerin klinik kullanımı

Purpose: This study aims to determine the usage frequency of long-acting injectable antipsychotics among bipolar disorder type 1 patients who presented to the Dicle University Faculty of Medicine Psychiatry and Mental Health outpatient clinic, the clinical characteristics of these patients, and the preferences of clinicians about these agents. &#x0D; Materials and Methods: Our study included 111 patients older than 18 years old with bipolar disorder. The ’data of the patients were retrospectively obtained from electronic data records. The data were recorded in the data collection form prepared by the researchers with the support of the literature. &#x0D; Results: The rate of the patients who used long-acting injectable antipsychotics was 21.6%. Among the patients who used long-acting injectable antipsychotics, the rate of those who used second-generation long-acting injectable antipsychotics was 58.3%, and the most frequently preferred agent was paliperidone palmitate. The patients who were using long-acting injectable antipsychotics had significantly higher rates of not working and numbers of hospitalizations.&#x0D; Conclusion: Our results showed that long-acting injectable antipsychotics are preferred by clinicians in our outpatient clinic in the later stages of bipolar disorders and for patients with poor drug compliance, poor functionality, and more hospitalizations. Starting long-acting injectable antipsychotics in the early stages of bipolar disorders, even following the first attack, may increase treatment compliance, reduce the duration of hospitalization, and contribute to the functionality of patients.

HSD89 Impact of Race on Utilization of First Vs Second Generation Long-Acting Injectable Antipsychotics Among Medicaid Beneficiaries with Schizophrenia

Differential treatment patterns by race for mental health services for individuals with schizophrenia (SCZ), including disparities in antipsychotic prescription patterns, have been reported. This study assessed differences in utilization of first generation (FG) vs second generation (SG) long-acting injectable antipsychotics (LAIs) between Black and White Medicaid enrollees with SCZ and examined factors associated with FG vs SG LAI initiation, including race.