Long-acting Injectable Antipsychotics Prescription Research Articles

Long-acting injectable antipsychotics as maintenance therapy for schizophrenia during the COVID-19 pandemic: A micro-narrative review.

The coronavirus disease pandemic has presented healthcare systems with unprecedented challenges globally and substantially impacted the management of chronic diseases such as schizophrenia. This narrative review highlights the usefulness of long-acting injectable antipsychotics (LAIs) as maintenance therapy for patients with schizophrenia during the pandemic. The analysis of relevant literature and psychiatric survey data revealed diverse trends in LAIs prescription and patient adherence with oral antipsychotics. Although some studies have reported a decrease in LAIs prescriptions owing to pandemic-related disruptions, others have suggested stable patient adherence with oral antipsychotics. Approximately 70% of Japanese psychiatrists reported an increase in schizophrenia relapse rates in a survey, underscoring the critical role of LAIs in maintaining therapeutic stability. The potential benefits of LAIs with extended dosing intervals have been highlighted, including improving oral medication adherence and reducing the frequency of hospital visits. In conclusion, this review emphasizes the continued need for uninterrupted LAIs therapy in conjunction with community and home-based care despite the disruptions caused by the coronavirus disease pandemic. Further development of LAIs maintenance therapy strategies considering the ongoing pandemic and potential future public health emergencies are required.

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.

Three-year outcomes and predictors for full recovery in patients with early-stage psychosis

In the present study, various outcomes over 3-year period in patients with early stage psychosis including remission, recovery, relapse and medication adherence were investigated. Predictor for full recovery at year 3 was also examined. Three-year follow-up data in 534 patients with schizophrenia spectrum disorders (SSD) and psychotic disorder not otherwise specified (PNOS) were examined for overall outcome trajectories. The data of completers at year 3 (n = 157) were used to identify predictors for recovery using logistic regression. The rates of symptomatic remission and full recovery at 6-, 12-, 24-, and 36-month follow-up were 76.10, 69.20, 79.50, and 79.10%, and 22.80, 26.40, 28.60, and 39.60%, respectively. The rates of drop-out and relapse at 6-, 12-, 24-, and 36-month follow-up were 25.4, 29.5, 38.6, and 51.1%, and 3.7, 8.9, 19.0, and 38.9%, respectively. The rates of good adherence and prescription of Long-Acting Injectable Antipsychotics (LAIA) at 6-, 12-, 24- and 36-month follow-up were 87.8, 88.0, 91.9, and 93.9%, and 18.3, 21.7, 22.0, and 25.5%, respectively. Significant predictors for full recovery were duration of untreated psychosis (DUP), family intimacy and physical activity. We observed similar or better results on remission, recovery, and relapse rates compared to other previous studies. Effective psychosocial intervention should be provided to shorten the gap between remission and recovery rates and to address DUP, family issues, and exercise to enhance recovery.

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.

Predictors of long-acting injectable antipsychotic prescription at discharge in patients with schizophrenia and other psychotic disorders.

Long-acting injectable antipsychotics (LAIs) increase drug compliance and offer a reliable treatment option with stable pharmacokinetics. The aim of our study is to examine the rate and predictors of LAIs' prescription at discharge in inpatients with schizophrenia and other psychotic disorders. This retrospective study included 400 inpatients. Sociodemographic and clinical characteristics of the patients, the treatments applied in the past and prescribed at discharge were obtained from the hospitalization files. We compared these characteristics of those who were given LAI treatment at discharge to the patients who were given oral treatments. Thirty-nine percent of the patients were prescribed a LAI at discharge. Duration of illness was longer, and number of previous hospitalizations was higher in the LAI group. Nonadherence to the antipsychotics before the hospitalization, the previous history of LAI use, lack of insight at the admission and no previous antidepressant use were found as independent contributors to LAI prescription as the treatment of discharge in logistic regression analysis. Our study showed that LAIs are used at a high rate in our clinic; however, they are still initiated at a later stage, mostly in chronic patients with a lack of insight and compliance at admission.

First vs. multiple cannabis-induced psychotic episodes: Is inpatient treatment any different?

IntroductionRecent studies reported very high cumulative risk for a patient who had cannabis-induced psychosis to be diagnosed with a schizophrenia spectrum disorder.ObjectivesWe aim to compare sociodemographic and clinical characteristics, treatment and discharge plan in cannabis-induced first psychosis episode (CI-FEP) vs. multiple cannabis-induced psychotic episodes (CI-MEP) inpatients.MethodsRetrospective observational study of inpatient episodes with a discharge diagnosis of cannabis-induced psychosis between January 1st, 2018 and December 31st, 2019 in the Psychiatry Service of CHUSJ. Descriptive analysis of the results was performed using the SPSS software, version 26.0.ResultsOur sample included 61 inpatients, 19 (31.1%) with CI-FEP and 42 (68.9%) with CI-MEP. CI-MEP group had a median of 1±0,234 previous hospital admissions. CI-MEP group has 10,0 higher odds of being discharged in outpatient compulsory treatment (CI 95% 1,21-82,50, p=0,013) and 6.0 odds of being treated with long-acting injectable antipsychotics (LAIAP) (CI 95% 1,79-20,31, p=0,002) when compared to CI-FEP group. Having multiple cannabis-induced psychotic episodes was associated with future admissions to psychiatry unit (OR 4,85 (95% CI 1,23-19,15, p=0,018). We found no statistically significant differences regarding the sociodemographic and clinical characteristics, use habits and discharge plan between the two groups.ConclusionsPatients with multiple psychotic episodes due to cannabis use are more likely to have a LAIAP prescription, be discharged in compulsory outpatient regimen and be readmitted in to psychiatric inpatient unit. Considering the prevalence of CI-MEP and the risk of chronicity, we need integrative treatment programs to address the specificities of these patients.

The management of long-term treatment of patient with schizophrenia: results of a survey carried out in Italy

The management plan of patients with schizophrenia includes a multidimensional and integrated approach, consisting of pharmacological, psychological and psychosocial interventions. Among pharmacological approaches, the development of long-acting injectable antipsychotics (LAI) has radically changed the treatment plan of patients with schizophrenia. LAI can be successfully used in patients with multiple episodes, with partial or poor adherence to treatments and are very useful also in first episode patients. LAIs have been proven to be effective and with a good safety and tolerability profile, but they are still used in a few cases in the clinical routine practice. Therefore, the present study aims to evaluate attitudes and preferences of psychiatrists in the Italian routine care towards LAI and to identify the communication skills adopted in the routine care for the prescription of LAI. The final sample consists of 274 clinicians, recruited by phone call (n=257) and online (n=17). The main findings are: the psychoeducational approach is essential for improving patients' adherence to pharmacological treatments and their personal and social functioning; the involvement of family members is essential for improving adherence to treatments; LAIs are frequently used due to their efficacy and good tolerability profile, compared to first generation depot antipsychotics. Based on our findings, the ideal patient to be switched to LAI treatment is represented by a person with poor adherence to treatments, at the onset of the disorder, or with a poor tolerability to side effects.

Time to rehospitalization in patients with bipolar mania discharged on long-acting injectable or oral antipsychotics

ObjectiveThis study aimed to analyze time to rehospitalization in patients with bipolar mania discharged on long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs). Additionally, temporal trends in LAI prescription were investigated. MethodsPatients with bipolar mania discharged from the study hospital on antipsychotics between 2006 and 2018 were included. Survival analysis was used to compare time to rehospitalization within one year of discharge between patients discharged on LAIs and OAPs, and between FGA-LAIs (first- generation antipsychotic) and SGA-LAIs (second-generation antipsychotic). The Cochrane-Armitage trend test was used to test whether a temporal trend existed for LAI prescription rates during the study period. ResultsThe LAI group (n = 224) had a significantly lower rehospitalization rate and a significantly longer time to rehospitalization than the OAP group (n = 3836). Rehospitalization rate and time to rehospitalization were not significantly different between patients discharged on FGA-LAIs or SGA-LAIs. The LAI prescription rate grew significantly from 2.20% in 2006 to 11.58% in 2018 (Z = 5.5843, p < 0.0001). The prescription rate of SGA-LAIs also increased significantly (Z = 7.7141, p < 0.0001), but not the prescription rate of FGA-LAIs. LimitationsThe treatment allocation is not randomized in this retrospective study. Furthermore, various clinical characteristics were unavailable in our analysis, such as symptom severity, functional impairment, and others. ConclusionsLAIs were significantly superior to OAPs in reducing rehospitalization risk. However, SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. Use of LAIs increased significantly in discharged patients with bipolar disorder during the study period, especially SGA-LAIs.

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.

Use of Long-Acting Injectable Antipsychotic in an Inpatient Unit of a Community Teaching Hospital.

Background Individuals with Schizophrenia Spectrum Disorders (SSD) often experience significant impairment in educational, occupational, and psychosocial functioning. The clinical benefit of long-acting injectable antipsychotics (LAIs) in the management of patients with SSD is well established. SSD patients who are nonadherent to treatment have lower disease relapse and readmission rates when prescribed a LAI, compared to oral antipsychotics. Despite the reported advantages of LAIs, their prescription rates in clinical settings remain low. This pilot study aimed to determine the pattern of LAI prescription in psychiatric inpatients of a teaching community hospital in Brooklyn, New York. Methods A retrospective review of the charts of patients discharged from the psychiatric units of the hospital from September 1, 2017, through September 30, 2017, was conducted. Frequencies and proportions for demographic and disease-related characteristics were calculated. Pertinent continuous variables were recoded into categorical variables. Chi-square-tests or Fisher's exact tests were performed for categorical variables. The one-sample Shapiro-Wilk test (for sample size < 50) was used to check for the normality of distribution of continuous variables. Statistical significance was defined as p ≤ 0.05. Results Forty-three (70%) of the patients discharged from the inpatient unit during the study period had SSD and were eligible for a LAI. Their ages ranged from 20 to 71 years (mean = 41 years), and more than two-thirds were male. Less than half of the eligible patients (n = 19; 44%) were prescribed a LAI, most of whom were male (n=16; 84%). An association between age group (patients aged 41 years or younger) and LAI use was observed (p < 0.05), while gender, employment status, living arrangement, length of hospital stay, recent hospitalization, and cooccurring substance use disorder were not. Conclusion LAI prescription rate at the inpatient psychiatric unit of the hospital was marginally higher than those reported in most studies. Age appears to influence LAI use during the study period. Initiatives that increase LAI prescription rate for all eligible patients admitted to inpatient psychiatric unit should be encouraged.

Attitudes toward long-acting injectable antipsychotics among patients with schizophrenia in Japan.

BackgroundLong-acting injectable antipsychotics (LAIs) are regarded as an important alternative to oral medication for patients with schizophrenia. However, LAIs remain under-utilized in clinical practice.AimsThe aims of this investigation were to 1) obtain information on patients’ attitudes toward LAIs and 2) assess factors associated with patients’ acceptance of LAIs, and 3) identify predictors of the discrepancy between patients and referring psychiatrists’ opinions regarding the appropriateness for LAIs.MethodsAnonymized data were collected from a questionnaire distributed to 159 patients with schizophrenia and their referring psychiatrists at three psychiatric hospitals between February 2014 and July 2014. The patients completed an original questionnaire developed to evaluate their attitudes regarding LAIs. Regarding the appropriateness of LAI prescription, patients and their referring psychiatrists were asked to rate, on a 5-point scale, how appropriate they felt the depot prescription was for the patients. The participants also answered instruments to assess symptom severity, antipsychotic-induced extrapyramidal symptoms, functions, quality of life, and self-esteem levels.ResultsPatients currently on LAIs have favorable attitudes toward LAIs with respect to side effects, relapse prevention, efficacy, pain, and cost. Expectation of relapse prevention was significantly associated with patients’ acceptance of LAIs (answering that those drugs are appropriate for their own treatment). In addition, the discrepancy between the patients’ and referring psychiatrists’ opinions regarding the appropriateness of LAI treatment was significantly associated with symptom severity, expectation of relapse prevention, belief that LAIs are painful, and belief that LAIs offer a reduced range of antipsychotic choices.ConclusionAttitudes toward LAIs need to be considered when deciding whether to prescribe this formulation. Access to information on LAIs, including their benefit in relapse prevention, might enhance the acceptance and use of this formulation among patients with schizophrenia.

Long Term Efficacy of the Treatment with Olanzapine Pamoate, Risperidone and Aripiprazole Monohydrate

The use of long-acting injectable antipsychotics (LAIs) is considered to be an important treatment option, especially in early stages of schizophrenia. The aim of this study was to evaluate the efficacy, safety and sustained remission in schizophrenia patients treated with three of the available LAIs substances: olanzapine pamoate, risperidone microspheres and aripiprazole monohydrate. A retrospective chart review study evaluating the efficacy of LAIs compared to oral antispychotics during a five years period was performed. Of the 102 patients included in the study, 52 (50.9%) continued LAIs: olanzapine pamoate (n = 20, 38.4%), risperidone microsphere (n = 22, 42.3%), aripiprazole monohydrate (n = 10, 19.3%). In the LAIs group the number of relapses was smaller than in the oral antipsychotics group (12 vs. 23, P [ 0.05) as well as the number of admissions (15 vs. 30, P [ 0.05). In conclusion, relapse in schizophrenia is strongly related to nonadherence. LAIs prescription overall was underutilized despite their efficacy. Future randomized studies are needed to evaluate the long term efficacy of LAIs compared to oral treatment.

P.3.f.026 - The role of psychiatrists’ attitudes on the prescription of long-acting injectable antipsychotics

Gastroesophageal reflux disease (GERD) may cause airway symptoms and some airway diseases exacerbate GERD symptoms. Asthma and allergic rhinitis (AR) have been identified as united airway disease because of their similar epidemiology and pathophysiology. Asthma has been considered a risk factor to develop GERD. However, the association between AR and GERD is not clear. We tried to investigate whether AR could increase the development of GERD.Children diagnosed as AR without a prior history of GERD were conducted from the National Health Insurance Research Database between 2000 and 2005. After propensity score matching, we enrolled 36,588 children with AR and 36,588 non-AR children as the controls. Cox regression models were adopted to calculate the hazard ratio (HR) of GERD.AR children had a significantly increased risk of GERD than non-AR children (adjusted HR 1.91, 95% CI = 1.73–2.11, p < 0.001), especially in the age less than 6 years old (adjusted HR 2.68, 95% CI = 1.64–4.38, p < 0.001). The risk factor related to increased risk of GERD including age, gender, and chronic sinusitis.AR is a risk factor associated with the development of GERD in children.

Long acting injectable antipsychotics in the treatment of schizophrenia: a review of literature

Antipsychotic medications are the key of the treatment in schizophrenia, and a large body of data confirms the value of ongoing and continuous antipsychotic pharmacotherapy in controlling symptoms and preventing relapse. Even so medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Estimates is ranging from 40% to 90%. The introduction of the long acting injectable antipsychotics (LAI) had as its primary objective to overcome the poor adherence. This review focuses on the role of LAI in the treatment of schizophrenia, particularly on new generation antipsychotics. The existing literature, with an emphasis on clinical evidence, is assessed. Both advantages and limitations are discussed. Clinical evidence suggest that treatment with LAI is associated with a better outcome, both global and as a reduced number of rehospitalization, and better adherence. The LAI ensure a better bioavailability, more predictable correlation between drug dose and plasma concentrations, a better pharmacokinetic profile allowing the prescription of lower doses and less risk of side effects. First generation antipsychotic LAI (FGA-LAI) share with their equivalent oral compounds an increased susceptibility to induce extrapyramidal symptoms and tardive dyskinesia, with minor differences between the compounds. The second-generation LAI (SGA-LAI), as their oral formulations, compared to first generation antipsychotics, have the advantage of not causing movement disorders, but their use is complicated by the delayed release (risperidone) and the risk of the syndrome post-injection (olanzapine) and the high cost (paliperidone). Despite identified advantages, LAIs are not used as widely as might be expected. It would seem that clinicians are at least partly responsible for this, influenced by our own misperceptions (e.g., that LAIs are not acceptable to patients) and misinformation (e.g., increate side effect risk). Current guidelines on the treatment of schizophrenia recommend the use of LAI in patients who have demonstrated non-adherence or recurrent relapses related to poor or no adherence and underline the importance of patient preference. The prescription of LAI will increase in coming years as more number of LAI will be available and the increasing use of compulsory community treatment may contribute to this.

Clinicians’ Attitudes Toward the Use of Long-Acting Injectable Antipsychotics

Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists' attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for second-generation LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians' attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.

Treatment Adherence with Early Prescription of Long-Acting Injectable Antipsychotics in Recent-Onset Schizophrenia

Although response to treatment for the first episode of schizophrenia is generally favourable, nonadherence with the treatment is the first cause of relapse and rehospitalisation within the next few years. Long-acting injectable antipsychotics (LAIAs) combine the advantages of the newer antipsychotics and the long-acting formulation. The evaluation concerns 25 schizophrenic patients hospitalised for the first time, treated with risperidone long-acting injectable (RLAI) associated with reintegration methods, and followed up for at least 18 months. Clinical observation was completed using Clinical Global Impression (CGI) scale and Global Assessment of Functioning (GAF). Clinical improvement was coupled with a good reintegration rate, very few relapse, or rehospitalisation. Bimonthly injection combined with psychosocial methods improved interactive followup, and therefore patients' compliance with the treatment. Treating with LAIA as early as possible, from the first episode if possible, can reduce relapse, number and duration of rehospitalisation, and cognitive symptoms and improve the quality of life and prognosis.