Long-acting Injectable Treatment Research Articles

Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study

Objective Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. Methods The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. Results Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. Conclusions In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.

Rilpivirine and cabotegravir trough concentrations in people with HIV on long-term treatment with long-acting injectable antiretrovirals.

Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. Sixty-seven PWH were identified. LAI treatment duration was 216 ± 80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P < 0.05). No differences were found in rilpivirine (160 ± 118 versus 189 ± 81 ng/mL; P = 0.430) and cabotegravir (1758 ± 807 versus 1969 ± 802 ng/mL; P = 0.416) trough concentrations in males (n = 55) versus females (n = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n = 9) versus non-obese participants (1916 ± 905 versus 1606 ± 576 ng/mL; P = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.

Implementation of a Pharmacist-Led, Long-Acting, Injectable Cabotegravir/Rilpivirine Program for HIV-1 at Health System-Based Clinics in the New York Metropolitan Area.

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.

Effect of long-acting antipsychotic treatment on psychiatric hospitalization rate in early psychosis patients: a naturalistic study.

The effectiveness of long-acting injectable (LAI) antipsychotics in preventing relapses of first-episode psychosis is currently debated. The study aimed to investigate the number of psychiatric hospitalizations comparing the LAI cohort versus the oral cohort during different phases of the illness, pre-LAI treatment, during LAI treatment, and after LAI treatment. A naturalistic study was conducted on two independent cohorts of early psychosis patients receiving treatment from a specific early intervention service. The first cohort comprised 228 patients who received LAIs, while the second cohort comprised 667 patients who had never received LAIs. This study was designed as a longitudinal observational study conducted within a naturalistic clinical setting in two cohorts of early psychosis patients. Repeated series ANCOVA (ANCOVA-r) was used to study the number of hospitalizations in the different study periods (T1 = from the date of the first psychiatric record to the beginning of the mirror period; T2 = the mirror period; T3 = from the LAI implementation to the LAI discontinuation; and T4 = from the LAI discontinuation to the end). In all cases, discontinuation of LAI involved the return to oral treatment. In all, 35 patients had not T4 as they were still on LAI treatment at the time of database closing (September 2020), and their data were not included in the analysis of the effect of the LAI discontinuation. The patients in the LAI cohort were younger, more frequently males, presented more schizophrenia diagnoses, and had a higher number of hospitalizations (2.50 ± 2.61 versus 1.19 ± 1.69; p < 0.001) than the oral cohort. The number of hospitalizations at the end of the follow-up was higher in the LAI cohort [0.20 (standard deviation (SD)) = 0.79] versus 0.45 [SD = 0.45 (SD = 1.13); F(23.90), p < 0.001]. However, after the introduction of LAIs, the differences in hospitalization rates between the two cohorts became less pronounced. Once LAI treatment was ceased, the hospitalization rate increased again. In our study, early psychosis patients receiving LAIs experienced a greater decrease in hospitalizations after introducing the LAI treatment than those treated solely with oral medication. These findings support using LAIs as a viable strategy for preventing rehospitalization and improving the overall course of treatment for individuals with early psychosis.

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.

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.

Integrating long-acting injectable treatment to improve medication adherence among persons living with HIV and opioid use disorder: study protocol

BackgroundOral antiretroviral therapy (ART) has been effective at reducing mortality rates of people with HIV. However, despite its effectiveness, people who use drugs face barriers to maintaining ART adherence. Receipt of opioid agonist treatment, in the context of HIV care, is associated with medication adherence and decreased HIV viral loads. Recent pharmacological advancements have led to the development of novel long-acting, injectable, medications for both HIV (cabotegravir co-administered with rilpivirine) and OUD (extended-release buprenorphine). These therapies have the potential to dramatically improve adherence by eliminating the need for daily pill-taking. Despite the extensive evidence base supporting long-acting injectable medications for both HIV and OUD, and clinical guidelines supporting integrated care provision, currently little is known about how these medications may be optimally delivered to this population. This paper presents the study design for the development of a clinical protocol to guide the delivery of combined treatment for HIV and OUD using long-acting injectable medications.MethodsThe study aims are to: (1) develop a clinical protocol to guide the delivery of combined LAI for HIV and OUD by conducting in-depth interviews with prospective patients, clinical content experts, and other key stakeholders; and (2) conduct This single group, open pilot trial protocol to assess feasibility, acceptability, and safety among patients diagnosed with HIV and OUD. Throughout all phases of the study, information on patient-, provider-, and organizational-level variables will be collected to inform future implementation.DiscussionFindings from this study will inform the development of a future study to conduct a fully-powered Hybrid Type 1 Effectiveness-Implementation design.

Prevention in Practice: Improving Communication on the Benefits of Treatments for Schizophrenia

AbstractIntroductionAntipsychotic treatment can help improve outcomes in schizophrenia by reducing the risk of relapse and psychiatric hospitalization, and increasing rates of remission and recovery, particularly when used early in the disease course. However, adherence to oral antipsychotics is often poor. Long-acting injectable (LAI) antipsychotic formulations are associated with significant improvements in treatment adherence compared with oral medications, but LAIs are not widely used in early-phase schizophrenia.MethodsAn educational training program, called “Prevention in Practice,” was developed to offer clinicians a range of innovative, web-based, patient-centered resources, including virtual role-play and educational films, that aim to improve communication between clinicians and patients and help progress care for patients with early-phase schizophrenia. The program was based on findings from the PRELAPSE study, in which clinicians received training to improve communication with patients. The PRELAPSE trial was a cluster randomized study conducted in 39 mental health centers across 19 US states. Sites were randomized to encourage treatment with the LAI aripiprazole once-monthly 400 mg (AOM 400) or to provide treatment as usual. Eligible patients had a diagnosis of schizophrenia, &lt;5 years of lifetime antipsychotic use, and were aged 18–35 years. The objective was to evaluate whether use of the LAI delayed time to first hospitalization in early-phase schizophrenia, compared with usual care. Clinicians received training on the rationale for LAI use in early psychosis, transitioning to LAIs, and discussing LAIs with patients and families. Communication training included the principles of shared decision-making, suggested responses to frequently asked questions, and role-playing.ResultsIn PRELAPSE, the sites randomized to encourage LAI treatment enrolled 234 patients and the sites randomized to usual care enrolled 255 patients. Training clinicians to improve their communication with patients made a difference—91% of patients with early-phase schizophrenia were willing to use LAI treatment at least once in the first 3 months of the study. Furthermore, the results showed that AOM 400 significantly prolonged time to first psychiatric hospitalization compared with usual care (hazard ratio: 0.56 [95% confidence interval: 0.34, 0.92]; p=0.02).ConclusionsOffering clinicians training to improve their communication with patients, through techniques such as shared decision-making and motivational interviewing, may increase LAI use in early-phase schizophrenia. ”Prevention in Practice” is now available in in different countries and languages.FundingOtsuka Pharmaceutical Development &amp; Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).

Long-acting new generation antipsychotics in the maintenance treatment of bipolar disorders

IntroductionMaintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.ObjectivesWe aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.MethodsClinical records of 56 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated. Descriptive statistical analysis was performed with Statistical Package for the Social Sciences (SPSS).ResultsNearly half of the patients were male (n:29, 52%). 49,1% of the patients were married. The mean age was 37.1±12.2 years and the mean duration of education was 11.1±4.2 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (64,7%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. We found a significant reduction in the number of manic episodes after long-acting treatment (p&lt;0.001), but we could not find any difference for depression. Ten of the patients discontinued the treatment due to the side effects, extrapyramidal side effects were the most common side effects. Eight of the patients were switched from paliperidone treatment to aripiprazole treatment due to side effects, especially hyperprolactinemia. Relapse was observed in 46,4% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.ConclusionsLAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.Disclosure of InterestNone Declared

Can multisite clinical trial results change clinical practice? Use of long-acting injectable risperidone nationally in the Veterans Health Administration

BackgroundMultisite practical clinical trials evaluate treatments in real-world practice. A multisite randomized Veterans Health Administration (VHA) cooperative study (CSP#555) published in 2011 compared the first long-acting injectable (LAI) second-generation antipsychotic (SGA), Risperidone Consta®, in veterans with a diagnosis of schizophrenia or schizoaffective disorder, to oral antipsychotics, with unexpected null results for effectiveness and cost-effectiveness. Whether null results of this type could change VHA practice has not been studied.MethodsA longitudinal observational analysis was used to evaluate the impact of the trial findings on VHA clinical practices. National administrative data compared new starts on LAI risperidone during the 4 years before the publication of CSP#555 in 2011 to new starts on LAI risperidone during the 4 years after.ResultsAmong 119,565 Veterans with the indicated diagnoses treated with antipsychotics from 2007 to 2015, the number and proportion of new starts on LAI risperidone declined significantly following the study publication, as did the total number of annual users and drug expenditures. However, data from 2007 to 2010 showed the decline in new starts actually preceded the publication of CSP#555. This change was likely explained by the increase in new starts, total use, and expenditures on a newer medicine, LAI paliperidone, a 4-week LAI treatment, in the 2 years prior to the publication of CSP#555.ConclusionsThe declining use of LAI risperidone likely primarily reflects the substitution of a longer-acting LAI SGA, paliperidone, that came to market 2 years before the study publication, a substitution that may have been reinforced by null CSP#555 study results for LAI risperidone.

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST)

Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94-1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Lundbeck and Otsuka.

Patient preferences and health state utilities associated with the treatment process of antiretroviral therapy for people living with HIV

PurposePeople living with HIV (PLHIV) have reported challenges associated with daily oral antiretroviral therapy (ART), including missed doses, negative psychological impact, and difficulty remaining discreet while at home or traveling. Recently approved long-acting injectable (LAI) ART may help eliminate these concerns. The purpose of this study was to examine patient preferences and estimate health state utilities associated with oral and LAI treatment for ART.MethodsFour health state vignettes were developed based on published literature, clinician interviews, and a pilot study. All vignettes included the same description of HIV, but differed in treatment regimens: (A) single daily oral tablet, (B) two daily oral tablets, (C) injections once monthly, and (D) injections every two months. PLHIV in the UK reported their preferences and valued the health states in time trade-off utility interviews.ResultsThe sample included 201 PLHIV (83.1% male; mean age = 44.9y). The health states frequently selected as most preferable were D (n = 119; 59.2%) and A (n = 75; 37.3%). Utility differences among health states were relatively small, which is typical for treatment process utilities (mean utilities: A, 0.908; B, 0.905; C, 0.900; D, 0.910). Statistically significant differences in utility were found for one vs. two tablets and injections every month vs. every two months (p < 0.001). Participants’ quotations highlight the wide range of reasons for treatment process preferences.ConclusionsCurrent results indicate that many PLHIV would prefer LAI ART. The reported utilities may be useful in economic modeling comparing oral vs. LAI ART.

Long-acting Injectable Antipsychotics during the COVID-19 pandemic in schizophrenia: An observational study in a real-world clinical setting

The COVID-19 pandemic is having an important impact on the practice of mental health services and on schizophrenia patients, and heterogeneous and conflicting findings are being reported on the reduction of long-acting injectable (LAI) antipsychotics use.Aims of the study were to assess the total number of patients treated with LAI, the start of novel LAI and the discontinuation of LAI treatments, analyzing register data of the first year of the pandemic, 2020, compared to a pre-pandemic reference year, 2019.Data from two outpatient centers were retrieved, for a total of 236 participants in 2020: no significant differences were observed comparing 2020 and 2019 when considering the total number of patients on LAI treatment (p = 0.890) and the number of dropouts (p = 0.262); however, a significant reduction in the start of LAI was observed (p = 0.022). In 2020, second generation LAI were more prescribed than first generation LAI (p = 0.040) while no difference was observed in 2019 (p = 0.191).These findings attest the efficacy of measures adopted in mental health services to face the consequences of COVID-19 and shed further light on the impact of the pandemic on the clinical practice of mental health services and on the continuity of care of people with schizophrenia.

Frequency of genotypic factors possibly associated with cabotegravir/rilpivirine failure in antiretroviral treatment-naïve and -experienced HIV-1- infected population.

The long-acting injectable (LAI) cabotegravir (CAB) and rilpivirine (RPV) treatment offers important advantages over oral ART (antiretroviral therapy), however baseline factors possibly contributing to the CAB/RPV treatment failure were identified. The purpose of this study was to describe the frequency of virologic factors previously influencing efficacy of this treatment, namely RPV and CAB resistance-associated mutations (RAMs) and A1/A6 subtype among naïve and treatment-experienced HIV-1-infected patients from Poland. The following datasets of HIV-1 sequences were analysed: 4809 protease and reverse transcriptase (PR/RT) sequences obtained from 4649 Polish Caucasian patients (4122 naive and 687 non-naïve) supplemented with integrase (PR/RT/INT) sequences in 1217 cases (942 naïve and 275 non-naïve). Sub-subtypes A were assigned by phylogenetic methods. Major and minor CAB and RPV RAMs were determined according to the IAS-USA 2019 list, while minor RAMs were additionally defined based on the Stanford database algorithm. Subtype A1/A6 frequency ranged from 6.11% in ART failing cases with PR/RT sequences only, to 15.92% for the PR/RT/INT treatment-naïve dataset, while RPV RAMs were found in up to 5.89% of treatment-naïve and 14.56% of ART failing cases. Regardless treatment history, only <1% sequences had combination of two factors (RPV RAMs and A1/A6 subtype). Furthermore, CAB RAMs were found in 1.27% of treatment-naïve and 14.54% of experienced patients. Despite notable frequency of subtype A1/A6 or CAB/RPV RAMs analysed separately, combination of at least two factors previously associated with failure or this treatment is rare. As subtype A1/A6 becomes more common across real-life cohorts continued subtyping and RAM screening will remain of key importance for LAI treatment implementation. Sequence data from this article have been deposited in GenBank under accession numbers: GU906860, GU906864, GU906871-GU906874, JQ305750-JQ305791, KC409134-KC409222, KM057341-KM057362, KM283892-KM284490, KT340108-KT340205, MZ468643-MZ468894, MZ671788-MZ671823, OP298017-OP302727.

Differences in Antiretroviral Adherence Behaviors, Treatment Success, and Eligibility for Long-Acting Injectable Treatment between Patients Who Acquired HIV in Childhood vs. Those Who Acquired It in Adolescence/Early Adulthood.

This study investigates the impact of the age at which HIV was acquired on adherence. There was no difference in adherence between patients who acquired HIV in childhood vs. those who acquired it in adolescence/early adulthood (83% vs. 90%; p = 0.24), but achievement of virological/immunological efficacy (78.8% vs. 93.5%, p = 0.02) was less likely in patients who had acquired HIV in childhood. On the basis of resistance, patients who acquired HIV in adolescence/early adulthood tended to be more eligible for cabotegravir/rilpivirine treatment (90.3% vs. 80.3%; p = 0.11).

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

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

Long-acting new generation antipsychotics in the maintenance treatment of bipolar disorders

IntroductionMaintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.ObjectivesWe aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.MethodsClinical records of 44 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated.ResultsNearly half of the patients were male (n:24, 54%). 43,2% of the patients were married. The mean age was 36.6±11.9 years and the mean duration of education was 11.5±3.9 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (65.9%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. Ten of the patients discontinued the treatment due to the side effects and extrapyramidal side effects was the most common side effect. Relapse was observed in 25% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.ConclusionsLAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.DisclosureNo significant relationships.

Therapeutic drug monitoring of LAI antipsychotics as a predictor of clinical relapse: a one-year follow-up

IntroductionClinical relapses in schizophrenia remain a frequent event. Long-acting injectable (LAI) antipsychotics enhance adherence, but low blood levels can sometimes be observed despite an adequate posology. Nonetheless, the evaluation of this parameter is uncommon in clinical practice.ObjectivesTo explore the potential advantages of therapeutic drug monitoring (TDM) of LAIs as a predictor of relapse in clinically stable outpatients with schizophrenia.Methods44 individuals who had reached the pharmacokinetic steady state of LAI treatment (paliperidone, olanzapine, aripiprazole) underwent an anamnestic and psychopathological assessment. LAI blood levels were measured using liquid chromatography-mass spectrometry and classified as “in range” or “under range” according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guideline values. Individuals who relapsed during the one-year follow-up were compared to non-relapsers (Fisher’s exact test, χ2 or Mann-Whitney U). An exploratory binary logistic regression tested the role of other possible relevant predictors of relapse.ResultsNo differences were observed in baseline use of mood stabilisers (p=0.211), antidepressants (p=0.530), or prescribed LAI (p=0.563). Other comparisons are presented in the table: among these variables, in-range LAI levels were the only significant predictor of relapse (F=5.95, p=0.015; OR 0.04, 95%CI 0.02-0.56).Relapse (n=6)No relapse (n=38)pAge (years)41.33±10.7843.95±12.980.667Male4 (66.7%)21 (55.3%)0.600Illness duration (years)21.83±2.6419.13±11.820.289Previous acute episodes3.50±1.053.29±1.470.652PANSS-total49.33±14.8342.74±14.140.231In-range LAI2 (33.3%)32 (84.2%)0.006ConclusionsTDM of LAIs may optimise the clinical management of schizophrenia by highlighting a suboptimal dosage and a consequent higher relapse risk. Large-scale, drug-specific assessments are needed to confirm these findings.DisclosureNo significant relationships.

An 8-year longitudinal study of long-acting injectable (LAI) antipsychotics. Prescription trends and therapeutic drug monitoring to inform precision dosing

IntroductionDespite the widespread use of long-acting injectable (LAI) antipsychotics in schizophrenia and other disorders, there is a lack of longitudinal studies evaluating prescription trends and the usefulness of therapeutic drug monitoring (TDM) to inform dosing. Indeed, LAI prescription varies greatly among different areas of the world and over the years.ObjectivesAssess trends in LAI prescription in 2013-2020 at the Psychiatry Department of Bozen, Italy, and (2) analyze the correlation between dose of prescribed LAIs and blood levels measured via TDM.MethodsParametric statistics.ResultsLAIs were administered to 471 patients (x̅ age±SD=47.2±16.3 years; 56.3% men). The pie chart shows LAI treatment duration, i.e., from 1 to 7 consecutive years. The most used LAIs were haloperidol in 2013-2104 (26.5-31.8%) and paliperidone in 2015-2020 (22.5-25.7%). Dose adjustments were rather frequent, whereas the switch between LAI, due to moderate-to-side effects or unsatisfactory improvement of clinical status, was infrequent (41 cases/8 years). LAI interruption for the same reasons or non-compliance was even more infrequent (10 cases), but in 8 cases it happened for opposite reasons, i.e., achievement of patients’ stabilization and good compliance. The Table shows doses and plasma levels of LAIs. Correlations between doses and plasma levels were: haloperidol: r=-0.037, p=0.620; paliperidone: r=0.290; p=0.000; risperidone: r=0.219, p=0.006; fluphenazine r=0.358, p=0.000; aripiprazole: r=-0.051, p=0.610; olanzapine: r=-0.090, p=0.634.ConclusionsHaloperidol and paliperidone were the most used LAIs. Drug prescription trends and doses were stable over time. A significant positive correlation between dose and plasma level was found for paliperidone, fluphenazine, and aripiprazole.DisclosureNo significant relationships.

Perspectives on preparing for long-acting injectable treatment for HIV among consumer, clinical and nonclinical stakeholders: A qualitative study exploring the anticipated challenges and opportunities for implementation in Los Angeles County.

Long-acting injectable (LAI) antiretroviral therapy (ART) is a novel HIV treatment option for people with HIV. The first LAI ART regimen for HIV treatment received regulatory approval in the United States in January 2021. In February 2020, we collected qualitative data from 18 consumers and 23 clinical and non-clinical stakeholders to catalog anticipated individual-consumer, healthcare system, and structural levels barriers and facilitators to LAI ART implementation in Los Angeles County, California. Thematic analysis was guided by the CFIR implementation science model. CFIR constructs of intervention characteristics, individual characteristics, outer and inner setting, intervention characteristics, and implementation process emerged in analysis. Under intervention characteristics, anticipated facilitators included the relative advantage of LAI ART over pills for adherence and reduced treatment management burden and related anxiety; anticipated barriers included non-adherence to injection appointments, concerns of developing HIV resistance, discomfort with injection and cost. Anticipated facilitators based on individual characteristics included overall acceptability based on knowledge and positive beliefs about LAI ART. Participant noted several characteristics of the outer setting that could negatively impact implementation, such as medical mistrust, external policies, and LAI ART eligibility (i.e., to be virally suppressed prior to initiation). Participants were optimistic about the potential to decrease stigma but expressed that provider willingness for adoption could be hindered by challenges in organizational inner setting related to payment authorizations, increased staffing needs, medication procurement and storage, and provider and healthcare system readiness. Results from this pre-implementation study may inform rollout and scale-up of LAI ART in Los Angeles County.