Effectiveness Of Long-acting Injectable Antipsychotics Research Articles

Comparative Effectiveness of Long-Acting Injectable Versus Oral Antipsychotics in Patients With Schizophrenia Using the Prevalent New User Design and Subgroup Analyses.

We compared the effectiveness of long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in treating schizophrenia, focusing on whether the benefits of LAIs over OAs are evident even in the prevalent new user design and on effect heterogeneity. We conducted a prevalent new user cohort study using 2 administrative claims databases in Japan. We included patients with schizophrenia initiated on LAIs and propensity score-matched patients on OA. We compared the risks of psychiatric hospitalization and treatment discontinuation based on hazard ratios (HRs) using the Cox proportional hazards model. Effect heterogeneity was evaluated using subgroup analyses. In total, 2520 patients using LAI and OA were identified as matched cohorts. Long-acting injectable antipsychotics were associated with a higher psychiatric hospitalization risk than OAs (HR, 1.41; 95% confidence interval [CI], 1.06-1.88) in the entire population; however, LAIs were associated with lower risk in the group with a low proportion of days covered and psychiatric hospitalization history (HR, 0.51; 95% CI, 0.30-0.89). Long-acting injectable antipsychotics were associated with a lower risk of treatment discontinuation than OAs (HR, 0.76; 95% CI, 0.66-0.87) in the entire population; in the subgroup analyses, a consistent trend was observed in all strata (LAIs had a lower risk). Using a prevalent new user design, this study confirmed that LAIs have an advantage regarding treatment continuity. Long-acting injectable antipsychotics had higher psychiatric hospitalization risk than OAs in the entire population; however, this study suggested the presence of effect heterogeneity due to psychiatric hospitalization history.

Real-world effectiveness of long-acting injectable antipsychotic treatments in a nationwide cohort of 12,373 patients with schizophrenia-spectrum disorders

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.

Comparative effectiveness of long-acting injectable antipsychotics in patients with schizophrenia in Japan

ObjectiveTo compare the effectiveness of different long-acting injectable antipsychotics (LAIs) (aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol) in patients with schizophrenia in Japan. MethodsWe conducted a retrospective cohort study using two administrative claims databases. The study population consisted of outpatients with schizophrenia who initiated LAIs between May 1, 2015, and November 30, 2019. We directly compared the risk of psychiatric hospitalization and LAI discontinuation among the LAIs based on hazard ratios (HRs) using Cox proportional hazards regression models. ResultsThe numbers of eligible patients who initiated aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol were 303, 124, 73, and 123, respectively. Regarding psychiatric hospitalization, aripiprazole and paliperidone were associated with significantly lower risk compared to fluphenazine/haloperidol (HR of aripiprazole: 0.47, 95 % CI: 0.28–0.78, HR of paliperidone: 0.50, 95 % CI: 0.28–0.89); HR of risperidone showed the same trend as the aripiprazole and paliperidone. Regarding LAI discontinuation, aripiprazole and paliperidone were associated with significantly lower risk of LAI discontinuation compared to fluphenazine/haloperidol (HR of aripiprazole: 0.53, 95 % CI: 95 % CI: 0.35–0.80, HR of paliperidone: 0.57, 95 % CI: 0.35–0.92). Aripiprazole was also associated with a significantly lower risk compared to risperidone (HR: 0.56, 95 % CI: 0.32–0.98). ConclusionOur study suggests that aripiprazole and paliperidone are superior to fluphenazine/haloperidol in the risk of psychiatric hospitalization and LAI discontinuation. Aripiprazole is superior to risperidone in the risk of LAI discontinuation.

Long-Acting Injectable Antipsychotics in a Prescription Claims Data Source: A Validation Study.

BackgroundThe effectiveness of long-acting injectable antipsychotics (LAIAs) has been demonstrated in studies using prescription claims data. However, the validity of claims data for LAIAs has not been established.ObjectiveWe aimed to validate date dispensed, quantity dispensed and days supplied fields in prescription claims data, and to compare claims- and medical record-derived persistence estimates.MethodsWe evaluated LAIA dispensations in the Drug Programs Information Network prescription claims database from Manitoba, Canada against a random sample of medical records. Adults with one or more LAIA prescription between April 2015 and March 2016 were eligible. Results were stratified by LAIA type (first-generation LAIA, risperidone LAI or paliperidone LAI). Persistence estimates were assessed using Kaplan–Meier survival analysis and proportion of patients covered method.ResultsClaims data had high positive predictive value, ranging from 80.0% (95% CI 51.9–95.7) to 100.0% (95% CI 89.7–100.0), but low negative predictive value, ranging from 0.0% (95% CI 0.0–2.5) to 62.5% (95% CI 40.6–81.2). Quantity dispensed and days supplied exactly matched dose and dosing interval, respectively, for 99.7% and 97.1% of risperidone LAI doses, 100.0% and 76.6% of paliperidone doses, and 8.9% and 28.3% of first-generation LAIA doses. There were no significant differences in claims-derived versus medical record-derived persistence estimates.ConclusionsQuantity dispensed and days supplied provide valid estimates of dose and dosing interval for second-generation LAIAs, but underestimated these parameters for first-generation LAIAs. However, a large proportion of medical record-confirmed doses were missing from claims data, and dose and dosing interval are underestimated in claims data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00297-4.

Comparative effectiveness of long-acting injectable antipsychotics in a large naturalistic cohort across two European centers: Findings from the long-acting injectable antipsychotics collaborative (LAICO) study.

We aimed to evaluate and compare the use of the paliperidone palmitate-1 and 3-month (PP1M, PP3M), aripiprazole 1-month (A1M) and risperidone-LAI (RLAI) LAIs, using the following clinical outcomes: (1) the number of hospital admissions, (2) the number of hospital bed days, and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics, and biperiden. For that purpose, we designed a cross-sectional study, from 2015 to 2021, based on non-institutionalized population accessing care from mental health services in Spain and UK who were prescribed with LAIs during 1 year. A total of 993 patients using a LAI were included. PP1M and PP3M LAIs were associated with a decreased risk of being prescribed benzodiazepines (OR ​= ​0.35, 95%CI ​= ​0.16–0.80, p ​= ​0.012; OR ​= ​0.16, 95%CI ​= ​0.07–0.38, p ​= ​0.001, respectively) and oral antipsychotics (OR ​= ​0.23, 95%CI ​= ​0.09–0.54, p ​= ​0.001; OR ​= ​0.28, 95%CI ​= ​0.11–0.67, p ​= ​0.005, respectively) compared with RLAI. A1M was also associated with a decreased risk (OR ​= ​0.29, 95%CI ​= ​0.12–0.69, p ​= ​0.005) of antipsychotic prescription compared with RLAI. Moreover, PP1M and PP3M groups were treated with lower diazepam equivalents doses compared to the A1M (p ​= ​0.021, p ​= ​0.026) and RLAI groups (p ​= ​0.036, p ​= ​0.039). Finally, PP3M was associated with lower hospital admissions and bed days compared with A1M (p ​= ​0.001; p ​= ​0.001) and RLAI (p ​= ​0.018; p ​= ​0.001). In conclusion, paliperidone LAIs had a more favourable impact on overall bed usage compared to A1M and RLAI. Furthermore, paliperidone LAIs and A1M lowered the use of concomitant psychiatric medication versus the biweekly LAIs while differences in combination and augmentation practices between cohorts are also highlighted. Our findings could be useful for clinicians and their practice.

Real-world effectiveness of long-acting injectable antipsychotics to reduce 90-day and annual readmission in psychotic disorders: insights from a state psychiatric hospital.

To evaluate the effectiveness of long-acting injectable antipsychotics (LAI-a) in reducing the 90-day and annual readmission rates in schizophrenia inpatients. We conducted a cross-sectional study and included 180 adult patients with psychotic disorders discharged from 2018 to 2019 at a state psychiatric hospital. Descriptive statistics were used to measure the differences between the readmit and nonreadmit cohorts. Logistic regression model was used to measure the odds ratio (OR) for 90-day and annual readmission and was controlled for potential readmission risk factors. A lower proportion of patients receiving LAI-a were readmitted within 90-day (28.6%) and 1-year (32.4%) periods. Patients receiving LAI-a had lower odds of association for 90-day (OR 0.36, 95% confidence intervals [CI] 0.139-0.921) and annual (OR 0.35, 95% CI 0.131-0.954) readmissions compared to those discharged on oral antipsychotics. A higher proportion of inpatients who received fluphenazine LAI had 90-day (25%) and annual (18.2%) readmissions compared to other LAI-a. Utilization of LAI-a in patients with psychotic disorders can decrease both 90-day and annual psychiatric readmissions by 64% to 65%. Physicians should prefer LAI-a to reduce the readmission rate and improve the quality of life, and decrease the healthcare-related financial burden.

Improving the "real life" management of schizophrenia spectrum disorders by LAI antipsychotics: A one-year mirror-image retrospective study in community mental health services.

Schizophrenia poses a significant economic burden on the healthcare system as well as it has a significant impact on society at large. Reasons for such a high economic burden of schizophrenia include the frequent relapses and hospitalizations occurring in this disorder. We analyze the effectiveness of long-acting injectable antipsychotics (LAIs) compared to oral medications, in terms of "clinical process management" in a sample of patients with a diagnosis of schizophrenia spectrum disorder treated in community mental health centers. An observational, retrospective, mirror-image study was carried out to evaluate the effectiveness of LAIs compared to oral medications in terms of number of hospitalizations, emergency visits and planned visits on a 10-year period (from July 2007 to June 2017). Differences between first and second generation LAIs were also explored. Our findings show that hospitalization and emergency visits are significantly decreased with the use of LAIs, while planned visits are increased in patients treated with LAIs. Our results suggest that LAIs, in particular, second generation ones, reduce hospitalization rates and emergency visits, improving the economic burden of schizophrenia. Therefore, LAIs should be considered a cost-effective treatment in the management of schizophrenia under routine conditions.

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

ObjectiveThe effectiveness of long-acting injectable antipsychotics (LAIs) in elderly patients with schizophrenia remains unclear. This study aimed to compare the effect of LAIs with oral antipsychotics (OAPs) on time to rehospitalization within 1 year of discharge in this population. Other factors potentially associated with time to rehospitalization and trends in LAI prescription rates during the study period were also investigated. MethodsPatients over 60 years of age with schizophrenia discharged between 2006 and 2017 were followed for 1 year under naturalistic conditions. Survival analysis was used in the comparison between LAIs and OAPs regarding time to rehospitalization. Covariates thought to affect time to rehospitalization were also analyzed. The Cochran-Armitage trend test was used to evaluate whether a time trend existed for LAI prescription rates. ResultsThe LAIs group had a significantly lower rehospitalization rate and a significantly longer time to rehospitalization within 1 year of discharge than the OAPs group. Other factors that were associated with a longer time to rehospitalization included a shorter index hospitalization during the time of the study and fewer previous hospitalizations. No significant time trend was found for LAI prescription rates during the study period. However, the prescription rate of second-generation LAIs grew significantly. ConclusionLAIs were found superior to OAPs in preventing rehospitalization. A continuous increase in second-generation LAI prescription rate may be due to the better side-effect profile of second-generation LAIs compared to first-generation LAIs. More studies investigating the effectiveness of LAIs in elderly patients with schizophrenia are needed in the future.

Effectiveness of Long-Acting Injectable Antipsychotics in Schizophrenia: A Literature Review and Bayesian Meta-Analysis Informing Economic Considerations

BACKGROUND: Although the use of long-acting injectable antipsychotics (LAIs) is considered an important option in the management of schizophrenia two recent meta-analysis, which aimed to compare LAIs vs oral antipsychotics (OAPs) in terms of relapse rate, showed discordant results.AIM: To investigate factors affecting the efficacy of antipsychotics in terms of relapse prevention in the real-world and to estimate the management cost of an episode of relapse.METHODS: We conducted a literature search using MEDLINE/PubMed with the aim to extract efficacy, effectiveness and adherence data of LAIs and OAPs. The primary outcome was the relative risk (RR) of relapse between two strategies. The extracted RR were included in a series of Bayesian statistical models based on the starting hypotheses. The RR rates obtained from the meta-analysis have been used as input for an economic evaluation of the total costs associated with the management of the patient with schizophrenia from the Italian NHS perspective.RESULTS: The literature search identified 34 studies which met the inclusion criteria and were analyzed. According to the model that best explains the data, in the real-world setting the effectiveness with LAIs is greater than with OAPs, with a more pronounced effect for SGAs than for FGAs. Taking into account generation, route and frequency of administration, the RR decreased with lower administration frequency, with SGA LAI administered once every 90 days which is associated with the greatest reduction in the risk of relapse (-85%). When the results of the meta-analysis are used to feed an economic evaluation the results show that the SGA administered every 90 days is the strategy with the least expected cumulative cost both at 1 (€ 3,509) and 5 years (€ 19,690).CONCLUSION: SGA LAIs administered every 90 days seems to be the best option for the treatment of patient with schizophrenia from both the clinical and economic perspectives.An erratum to this article is available online at: https://doi.org/10.7175/fe.v20i1.1406

PP040 Hospitalization Costs In Schizophrenia: Long-acting Injectable Antipsychotics Versus Oral Antipsychotic Use

INTRODUCTION:Existing findings on effectiveness of long-acting injectable antipsychotics (LAIs) versus oral antipsychotics in preventing hospitalizations are inconclusive. This study was conducted to compare hospitalization costs between Medicaid patients diagnosed with schizophrenia who initiated a LAI and those who changed from one oral antipsychotic to another.METHODS:This retrospective cohort analysis used the Truven Health Analytics MarketScan® Medicaid claims database to study patients ≥18 years with schizophrenia. The two cohorts were: “LAI”, defined as initiating LAI (no prior LAI therapy) between 1 January 2013 and 30 June 2014; and “oral”, defined as changing from one oral antipsychotic to another during the same period. The first day of LAI or the new oral antipsychotic was the index date. A linear regression model was conducted to estimate hospitalization costs.RESULTS:The final sample included 2,861 (36.7 percent) LAI and 4,926 (63.3 percent) oral users. Compared to oral users, LAI patients were younger (mean (Standard Deviation, SD): 39.9 (13.2) versus 42.7 (13.1); p<.001) and had a lower mean Charlson Comorbidity Index score (mean (SD): 1.1 (1.9) versus 1.7 (2.3); p<.001). Of the 877 LAI initiators and 1,688 oral users who were hospitalized during the 1-year post-index follow-up period, the unadjusted mean hospitalization costs for LAI and oral users were USD32,626 and USD36,048, respectively. After adjusting for patient demographic and clinical characteristics, baseline medication use, and baseline ED or hospitalizations, the adjusted average hospitalization costs were USD1,170 lower in LAI initiators than oral users. None of the unadjusted or adjusted differences were statistically significant.CONCLUSIONS:This real-world study suggests that among hospitalized patients, hospitalization costs are lower in LAI initiators than in oral antipsychotic users, although the difference is not statistically significant. Our study is limited as our results are reflective of a multi-state Medicaid population. Future studies are warranted to confirm the results in non-Medicaid patient populations.

Effectiveness of long-acting injectable antipsychotics: a clinical perspective

The personal and societal costs of schizophrenia spectrum disorders are immense. Affected individuals may experience positive, negative and mood symptoms; medical and substance use comorbidities; and cognitive impairment that significantly...

Effectiveness of long-acting injectable antipsychotics in delusional disorders with nonprominent hallucinations and without hallucinations

The presence of nonprominent hallucinations in delusional disorder (DD) has been accepted by the current Diagnostic and Statistical Manual of Mental Disorders, 5th ed. A recent meta-analysis revealed that patients with schizophrenia treated with long-acting atypical antipsychotics showed a significant improvement in psychotic symptoms. However, little research has been conducted on DD. Our goal was to investigate demographic and clinical differences between two subgroups of DD patients, those with nonprominent hallucinations and those without hallucinations, and to determine treatment effectiveness of long-acting antipsychotics in these patients. We conducted a longitudinal observational study with a 6-month follow-up period in a clinical group of 45 DD outpatients. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale, and Hamilton Rating Scale for Depression-17 (HRSD-17) were used for assessment. Age at onset of DD, scores in baseline assessment scales, and drug compliance were included in the analysis as potential confounders. When uncorrected for influencing factors, patients treated with long-acting antipsychotics showed lower scores in PANSS positive and negative subscales. There were no statistically significant clinical subgroup×treatment group interactions for any of the scores in assessment scales at 6 months. After adjustment, patients treated with long-acting antipsychotics showed lower scores in the PANSS negative subscale and a tendency toward improvement in scores in the PANSS positive subscale. Our study suggests that risperidone long-acting injection and paliperidone palmitate long-acting injection may be useful in the treatment of DD patients, specifically those with nonprominent hallucinations.

EPA-0235 – Effectiveness of long-acting injectable antipsychotics (pplai and rlai) in the treatment of delusional disorder with non-prominent hallucinations

Recent meta-analysis in schizophrenia report that patients treated with long-acting injectable antipsychotics (LAI) show a significant improvement in hallucinations. However, little evidence supports their efficacy in non-prominent hallucinations in delusional disorder (DD) patients. To examine treatment effectiveness of LAI antipsychotics (PPLAI and RLAI) with other oral antipsychotics in DD with non-prominent hallucinations. A prospective and observational study was carried out by including 60 consecutive cases of DD outpatients, as part of the DEVCODEL Study. All patients were followed up for at least 6 months. Outcome variables: Scores in PANSS, HRSD-17 items, PSP for functionality, and C-SSRS for suicide. To investigate whether differences between treatment groups were biased by confounding variables, scores in assessment scales at 6 months served as dependent variables, and hallucinatory and treatment groups were included as between-subject factors when analysis of covariance (ANCOVA) was applied. 24(40%) patients had non-prominent hallucinations. Although not statistically significant, when uncorrected for influencing factors, DD patients receiving PPLAI or RLAI (n=27;45.5%) were less frequently treated with antidepressants (32%vs.68%) and showed lower suicidality (44.4%vs.55.6%). Patients treated with PPLAI or RLAI had lower scores in psychotic symptoms and suicidal ideation intensity, and higher functionality. After adjustment, patients with non-prominent hallucinations receiving PPLAI or RLAI showed a tendency of improvement in functionality, lower scores in PANSS positive (p=0.003) and negative (p=0.047) subscales, and suicidal ideation severity (p<0.001) compared to those treated with oral antipsychotics. Non-prominent hallucinatory patients treated with PPLAI or RLAI showed a significant improvement in psychopathology and suicidal ideation.

C.04.03 Relevance of study design for the effectiveness of long-acting injectable antipsychotics in schizophrenia

Serine and other amino acids that function as coagonists at the N-methyl-d-aspartate receptor (NMDAR) have been extensively investigated in schizophrenia (SCZ). However, studies comparing amino acid levels in body fluids of SCZ patients with healthy controls have yielded inconsistent results. We therefore conducted a meta-analysis (search: May 9, 2013) of serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels in blood and cerebrospinal fluid (CSF) obtained from adult SCZ patients and healthy controls. Standardized differences of means (SDMs) were computed, and heterogeneity, subgroup, sensitivity, and publication bias analyses were conducted. Blood serine levels were found to be significantly higher in SCZ patients compared to healthy controls (SDM = 0.280 (0.021–0.540), p = 0.034; N = 1671 subjects), whereas CSF serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels did not differ. Stratification by sex suggested that the case–control difference in blood serine levels particularly applies to male subjects. These results provide support for blood serine level aberrations in SCZ patients and warrant further research to disentangle the involvement of serine with SCZ in both sexes.

SASOP Biological Psychiatry Congress 2013 Abstracts

SASOP Biological Psychiatry Congress 2013 Abstracts