Long-acting Injection Research Articles

Predictors of Injection Visit Adherence in Those Receiving Injectable Cabotegravir/Rilpivirine.

There is limited data evaluating potential predictors of adherence to injection visits and the impact of late injections on viral suppression in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV. A retrospective cohort study was conducted among adult people with HIV (PWH) receiving LAI CAB/RPV for at least 6 months between May 2021 and August 2023. Data collected included demographics, office visit no-shows one year prior to switching to LAI CAB/RPV, injection visit no-shows, injections outside the dosing window, and virologic outcomes. Cox-proportional hazards regression was performed to evaluate predictors of no-show to injection visits or late injections. Included were 287 PWH with a median follow up time (IQR) of 450 days (344-548 days). Younger age [HR 0.97 (95%CI 0.95-0.98)] and ≥ 1 office visit no-show in the year prior to switch to LAI CAB/RPV [HR 2.03 (1.32-3.12]) were associated with having a no-show to an injection visit (32.1%). Male sex assigned at birth [HR 9.18 (1.26-66.9)] with a trend towards younger age [HR 0.98 (0.95-1.0)] were associated with having a late injection (15.3%). There was no relationship between late injections and having a detectable viral load or virologic failure (n=3) after switch to LAI CAB/RPV. Having office visit no-shows prior to switching to LAI CAB/RPV was associated with missed injection visits, and younger age was associated with both missed injection visits and late injections. Resources to reduce and manage missed injection appointments need to be considered when implementing LAI CAB/RPV.

Effectiveness of long-acting buprenorphine - A systematic review.

To analyse the evidence of the effectiveness of long-acting injection buprenorphine (LAI-B) in the management of opioid use disorder (OUD). Databases were searched for studies reporting on the effectiveness of LAI-B for the treatment of OUD. Risk of bias was assessed, and a narrative synthesis of data was presented. The study adhered to PRISMA guidelines and was registered with PROSPERO (CRD42023396033). Eighteen studies were included in the final review: two double-blind randomised control trials, two open-label randomised control trials, two retrospective cohort studies, one non-controlled pilot study, and eleven observational studies. In comparative trials, LAI-B was superior to placebo and superior or non-inferior to treatment as usual. LAI-B was positively associated with improvements in abstinence rates and patient-centred outcomes. There was limited data on the long-term effects of continuous LAI-B prescription. LAI-B is an effective treatment for OUD with advantages over existing forms of treatment. Patients reported high levels of medication satisfaction and there were no significant safety concerns. This review highlights the need for future research on long-term effectiveness outcomes, with participants of more varied demographics and psychiatric comorbidity, which is more reflective of the OUD population seen in community clinical settings.

“Ajudar” – a practice with people with mental disorders treated with long-acting injectables

Abstract Issue Mental Health problems are one of the main causes of disability and morbidity. We think it is pertinent to intervene, providing special care for people with mental disorders and their families. We developed the project “Ajudar” (“To Help”), in a municipality in Northern Portugal. Description of the problem “Ajudar” started in 2013. Its main goal is to contribute to reducing the impact of mental disorders. Its objectives are to identify people with mental disorders treated with long-acting injectables (LAI) and to promote treatment adherence. We identified the Health Units (HU) where these patients take the medication and verified their compliance. An informatic alert was issued when there was non-compliance and we participated in home visits when patients did not show up. We also checked the situation if there was involuntary treatment. We wanted to know if this practice contributed to treatment compliance and to reduce involuntary treatment. Results We gradually identified more people, from 47 in 2013 to 108 in 2024. In 2013, 7 people with mental disorders treated with LAI had an involuntary treatment, whereas in 2019 it was 4. We didn’t analyze data from 2020 to 2022, due to the COVID-19 pandemic. We don’t have the complete data from 2023 yet. Lessons Within the years of “Ajudar”, there was a more than twofold increase in the identified patients and a reduction of almost fourfold of the patients that had an involuntary treatment. Analyzing these data one must be careful due to small numbers bias. We think that a similar project is feasible in other settings. In our response to this Public Mental Health issue, we collaborated with everyone involved with these patients, from health profissionals to resources in the community (social services, community leaders, etc). Key messages • There was a decrease to almost ¾ in the number of patients that had an involuntary treatment. • Involvement with the community is key.

Clinical, Quality of Life, and Health Care Utilization Outcomes of Switching the Administration Route of Antipsychotic Medications Among People With Schizophrenia Spectrum Disorder: A Systematic Review and Meta-Analysis.

Using long-acting injectable (LAI) antipsychotic medications can improve the outcomes of patients with schizophrenia, such as reducing symptom severity and hospitalization risk. However, the outcomes of switching from oral to LAI antipsychotic medications are unclear. The purpose of this review is to provide a summary of the clinical, quality of life, and health care utilization outcomes of switching from oral to LAI antipsychotics among patients with Schizophrenia Spectrum Disorder. We thoroughly searched the PubMed, Scopus, PsycInfo, and CINAHL databases. To conduct the meta-analysis, we used the Comprehensive Meta-Analysis Program. Forty-one articles met our inclusion criteria. After switching to LAIs, symptom severity, the number of rehospitalizations, emergency department visits, and overall health care costs were reduced. Also, social functioning significantly improved. However, no differences were observed in the frequency of outpatient visits. Pharmacy costs were increased between pre- and post-LAI initiation. Our findings support evidence that changing the route of administration of antipsychotic medications from oral to long-acting intramuscular injections can improve the clinical, quality of life, and health care utilization outcomes in people with schizophrenia. Health care practitioners might consider encouraging LAI use earlier during treatment for schizophrenia for better clinical outcomes and to reduce health care utilization associated with treatment.

Correlates of post-hospitalization naltrexone adherence for alcohol use disorder

IntroductionHospitalizations present an opportunity to initiate naltrexone for patients with alcohol use disorder (AUD). Understanding factors associated with post-hospitalization adherence could inform practice. MethodsThis study is a secondary analysis of a clinical trial in which patients with AUD were randomized to oral (PO) versus long-acting injectable (LAI) naltrexone at hospital discharge. The outcome of this secondary analysis was naltrexone adherence 3 months after discharge, defined as receipt of at least 2 out of 3 monthly injections or the equivalent days of self-reported PO medication use (60 out of 90). We used baseline socio-demographics, substance use history, health status, healthcare utilization, and randomization arm to construct multivariable logistic regression models to identify correlates of adherence. ResultsWe evaluated patients who initiated naltrexone treatment, 124 randomized to PO and 120 to LAI (overall mean age 49 years, 80 % male, 51 % Black, 47 % unhoused, and 91 % with severe AUD). At 3 months, 50 % of patients were adherent. LAI naltrexone (aOR 3.88; 95 % CI 2.17–7.13), recent office visit (aOR 2.01; 95 % CI 1.10–3.72), and age (aOR per 10-year increase 1.37; 95 % CI 1.02–1.88) were associated with increased odds of adherence. Unhoused status (aOR 0.54; 95 % CI 0.30–0.98) and cocaine use (aOR 0.35; 95 % CI 0.17–0.71) were associated with decreased odds of adherence. ConclusionsLAI naltrexone for AUD at hospital discharge was associated with better adherence at 3 months vs PO. Access to LAI naltrexone and targeted interventions for patients with cocaine use or who are unhoused hold potential to improve naltrexone adherence.

Multi-level barriers and facilitators to implementing evidence-based antipsychotics in the treatment of early-phase schizophrenia.

Long-acting injectable (LAI) antipsychotic medications and clozapine are effective yet underutilized medical therapies in early intervention services. The purpose of this study was to conduct a pre-implementation evaluation of contextual determinants of early intervention programs to implement innovations optimizing LAI antipsychotic and clozapine use within a shared decision-making model. Semi-structured interviews explored barriers and facilitators to implementing LAI antipsychotics and clozapine in early intervention services. Participants were: prescribers (n = 2), non-prescribing clinicians (n = 5), administrators (n = 3), clients (n = 3), and caregivers (n = 3). Interviews were structured and analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0). Participants were supportive of using LAI antipsychotics, despite barriers (e.g., transportation, insurance coverage), while most were unfamiliar with clozapine (Innovation). Critical incidents (e.g., COVID-19) did not interfere with implementation, while barriers included lack of performance measures; stigma affecting willingness to take medication; and clozapine considered to be a "last resort" (Outer Setting). Treatment culture was described as client-centered and collaborative, and most participants indicated LAI antipsychotic use was compatible with clinic workflows, but some were in need of resources (e.g., individuals trained to administer LAI antipsychotics; Inner Setting). Participants on the healthcare team expressed confidence in their roles. Family education and collaborative decision-making were recommended to improve client/family engagement (Individuals). Participants related the importance of tracking medication compliance, addressing client concerns, and providing prescribers with updated guidelines on evidence-based treatment (Implementation Process). Results may guide implementation strategy selection for future programs seeking to optimize the use of LAI antipsychotics and clozapine for early-phase schizophrenia, when appropriate.

Comparative Effectiveness of Antipsychotics in Patients With Schizophrenia Spectrum Disorder

Antipsychotics are the cornerstone of maintenance treatment in schizophrenia spectrum disorders, but it is unclear which agents should be prioritized by prescribers. To investigate the clinical effectiveness of antipsychotics, including recent market entries, in comparison with oral olanzapine in relapse and treatment failure prevention among individuals with schizophrenia spectrum disorder. This comparative effectiveness research study with a within-individual analysis included data from Swedish health care registers of inpatient and specialized outpatient care, sickness absence, and disability pensions among all individuals aged 16 to 65 years who were diagnosed with schizophrenia spectrum disorder from January 1, 2006, to December 31, 2021, including an incident cohort and a prevalent cohort. Specific antipsychotics. The risks for psychosis relapse hospitalization and treatment failure (psychiatric hospitalization, death, or change in an antipsychotic medication) were adjusted for the temporal order of treatments, time since cohort entry, and concomitant drugs. Comparisons of all antipsychotics with oral olanzapine, the most commonly used antipsychotic, were investigated. Among the full cohort of 131 476 individuals, the mean (SD) age of the study cohort was 45.7 (16.2) years (70 054 men [53.3%]). During a median follow-up of 12.0 years [IQR, 5.2-16.0 years], 48.5% of patients (N = 63 730) experienced relapse and 71.1% (N = 93 464) underwent treatment failure at least once. Compared with oral olanzapine, paliperidone 3-month long-acting injectable (LAI) was associated with the lowest adjusted hazard ratio (AHR) in the prevention of relapses (AHR, 0.66; 95% CI, 0.51-0.86), followed by aripiprazole LAI (AHR, 0.77 [95% CI, 0.70-0.84]), olanzapine LAI (AHR, 0.79 [95% CI, 0.73-0.86]), and clozapine (AHR, 0.82 [95% CI, 0.79-0.86]). Quetiapine was associated with the highest risk of relapse (AHR, 1.44 [95% CI, 1.38-1.51]). For prevention of treatment failure, paliperidone 3-month LAI was associated with the lowest AHR (AHR, 0.36 [95% CI, 0.31-0.42]), followed by aripiprazole LAI (AHR, 0.60 [95% CI, 0.57-0.63]), olanzapine LAI (AHR, 0.67 [95% CI, 0.63-0.72]), and paliperidone 1-month LAI (AHR, 0.71 [95% CI, 0.68-0.74]). This comparative effectiveness research study demonstrated large differences in the risk of relapse and treatment failure among specific antipsychotic treatments. The findings contradict the widely held conception that all antipsychotics are equally effective in relapse prevention.

7854 Ablation Aberration: A Case of Thyroid Dermopathy Exacerbation in a Filipino Male Following Radioactive Iodine Ablation and Total Thyroidectomy Improved by Weekly Intradermal Long-Acting Glucocorticoid Injection

Abstract Disclosure: K.T. Lim: None. O.C. Dampil: None. Ablation Aberration: A Case of Thyroid Dermopathy Exacerbation in a Filipino Male Following Radioactive Iodine Ablation and Total Thyroidectomy Improved by Weekly Intradermal Long-Acting Glucocorticoid Injection Introduction: Thyroid dermopathy (TD) represents an unusual extrathyroidal presentation of Graves' disease (GD), impacting about 0.5–4% of patients. RAI treatment for hyperthyroidism is known to progress Graves' ophthalmopathy. RAI-induced TD exacerbation, however, is rare in literature. Here, we present a case of worsening TD and ophthalmopathy in a Filipino patient with GD who underwent definitive therapy for persistent hyperthyroidism. Clinical Case: A 44-year-old man with GD had bilateral lower extremity indurated, mildly erythematous plaques for 4 years. Hyperthyroidism persisted despite methimazole compliance, so he underwent RAI ablation two years earlier, total thyroidectomy a year later, and has been on levothyroxine since. Despite definitive treatment, his extrathyroidal symptoms worsened. A punch biopsy of the skin lesions revealed upper and mid-lower dermis mucin deposition, with occasional spindle-shaped and stellate fibroblasts, and mast cells. These histopathologic findings were consistent with pretibial myxedema. We assessed his thyroid function and found he was euthyroid with normal TSH (3.1 μIU/mL; reference range 0.27-4.20) and an elevated TRAb (35.73 IU/L; reference range <1.75). Physical examination revealed thickened skin, cobblestone-like plaques, and non-pitting edema on the pretibial, ankle, and pedal areas. A 3.5-cm-diameter, circumscribed, orange-peel-textured, indurated plaque covered his left ankle. Fluocinolone acetonide 0.025% w/w ointment was initiated. After 3 weeks, his cutaneous symptoms improved by 35%, albeit his left ankle circumscribed plaque improved marginally. Triamcinolone acetonide 40 mg/mL was injected into this and other nodular lesions at 4mg (0.1 mL) per 1-cm-diameter circular region. Each dose was equally dispersed by multipoint intradermal injections using a 1 mL syringe with a 0.5”x 25G needle. A week after intralesional triamcinolone injection and continuous topical steroid application on the non-nodular lesions, a 70% improvement in cutaneous manifestations was observed (from baseline) with the plaques becoming thinner and softer. After three weekly intradermal steroid injections, the circumscribed plaque had flattened (with residual hyperpigmentation), and the other plaques and nonpitting edema dissipated. Conclusion: Our experience with this patient highlights a paradoxical TD exacerbation following RAI ablation and definitive surgery for persistent hyperthyroidism in GD. It also reveals that weekly administration of multiple subcutaneous injections of a long-acting glucocorticoid alleviates lesions where topical ointment does not. Presentation: 6/1/2024

Characterizing long-acting injectable antiretroviral therapy eligibility and initiation at a safety net academic medical center in the southeastern United States.

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) extends dosing intervals from daily to every 8weeks. Equitable implementation requires anticipating and addressing barriers to use. We described LAI-CAB/RPV eligibility and initiation among persons with HIV (PWH) receiving care at a Southeastern US academic medical center. Methods: We included PWH ≥18years, in care 01/01/2020-12/31/2021, and participating in the UNC CFAR HIV Clinical Cohort. We characterized LAI-CAB/RPV eligibility, compared those with and without recent detectable viral load (VL), and described clinical outcomes on LAI-CAB/RPV. Results: Among 1672 PWH, 425 (25.4%) had LAI-CAB/RPV drug-resistance. Among 1238 LAI-eligible PWH, 8.9% had detectable VL. Median age was 53 (interquartile range 40, 61), 54.6% were non-Hispanic Black, and 73.6% male. Over one-third lived >50 miles from clinic, one-fifth were uninsured, and 7.4% reported hazardous alcohol use. Gaps in care (prior 12-month) were more common among PWH with detectable VL versus suppressed (23.1% vs 13.9%, p = 0.03). 6/47 initiated LAI-CAB/RPV had detectable VL prior to injection; >95% sustained suppression and those with detectable VL had a rapid decline in viremia. Conclusions: Three-quarters of PWH were eligible for LAI-CAB/RPV, but equitable implementation may require addressing challenges such as distance to care, inconsistent care engagement, and other comorbid conditions, particularly for PWH with viremia.

Engagement Along the PrEP Care Continuum Among Men Who Have Sex with Men in China: A Systematic Review and Meta-analysis.

Pre-exposure prophylaxis (PrEP), including daily oral, on-demand, and long-acting injectable (LAI), is a promising HIV prevention intervention for men who have sex with men (MSM). We conducted a systematic review on engagement with the PrEP continuum among MSM in China. A total of 756 studies were initially identified and 36 studies were included (N = 26,021). In the 20 studies (N = 13,886) examining PrEP awareness, 32.4% (95% CI: 25.1-40.7) of MSM were aware of PrEP. In the 25 studies (N = 18,587) examining willingness, 54.5% (95% CI: 41.9-66.5) MSM indicated they were willing to use PrEP. The pooled prevalence of PrEP uptake from 9 studies (N = 6,575) was 4.9% (95% CI: 1.4-15.8%), while pooled estimates of adequate adherence from five studies (N = 2,344) among MSM on PrEP was 40.7% (95% CI: 20.0-65.2%). Subgroup analyses suggested studies conducted after 2015 (versus before) tended to report higher awareness and uptake. Awareness was highest for daily oral PrEP, followed by on-demand, and LAI PrEP; willingness to use was highest for LAI PrEP. The operationalization of willingness and adherence constructs varied across studies and complicated the interpretation of pooled estimates. This review revealed gaps in the PrEP care continuum among MSM in China, with relatively low awareness and uptake (in contrast to willingness and adherence) as the major potential barriers to widespread implementation and the need for a unified approach to defining and measuring PrEP outcomes.

Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants.

GB-5001 is an intramuscular (IM) formulation of donepezil under development for the treatment of Alzheimer's disease. The objective of this study was to develop a population pharmacokinetic (PK) model for donepezil in both IM and oral formulations, and to optimize the IM dosage of GB-5001 using bioequivalence (BE) simulation. A population PK model of donepezil was developed using NONMEM. It was based on plasma concentration data from a Phase 1 dose escalation study, which involved a single administration of donepezil IM formulation at doses of 70, 140, and 280mg, and the oral formulation at 10mg. The model was evaluated based on goodness-of-fit plots, conditional weighted residuals, visual predictive checks, and bootstrapping. BE simulations were conducted using a parallel design between various doses of the IM formulation and the 10-mg dose of oral formulation. The PKs of donepezil were best described by a two-compartment model, which incorporated distinct absorption compartments for the IM (dual first-order absorption and simultaneous zero-order absorption with lag time) and oral (first-order absorption with lag time) formulations. Based on the simulation results, an IM dosage range of 210-215 mg in a sample size of over 92 was estimated to achieve a success rate of approximately 80% for BE. The population PK model well explained the PKs of donepezil following administration of both the IM and oral formulations. This model could be applied for the design and dose selection of future BE trials. ClinicalTrials.gov identifier, NCT05525780.

Long-Acting Injectable Antipsychotic Medication Use in Youth: A Systematic Review of the Literature Along with MedWatch Safety Data and Prescriber Attitudes.

Objectives: Long-acting injectable (LAI) antipsychotic medications are being prescribed to children and adolescents along a broad age range from 2 to 17 years old. However, there is no U.S. Food and Drug Administration (FDA) approved indication for the use of any LAI in a pediatric population. The goal of this article is to perform a systematic literature review regarding the use of LAIs in a pediatric population, to obtain pediatric LAI safety data, and to survey prescriber attitudes regarding LAI use in youth. Methods: A search for relevant articles between June 1986 and June 2021 was conducted. Safety data were obtained from FDA MedWatch postmarketing adverse event reports regarding LAI use in children and adolescents. A survey of practicing Child and Adolescent Psychiatrists in Wisconsin was done regarding the use of LAIs in youth. Results: The predominant reasons for LAI use in youth were illness severity and treatment noncompliance. Twenty-six of 30 identified studies and reports favored LAI use in youth, but were of low to very low quality. Overall, 587 FDA MedWatch reports between June 1986 and June 2021 were identified. Most adverse events occurred in modest numbers. Extrapyramidal symptoms accounted for 18% of all MedWatch reports, neuroleptic malignant syndrome accounted for 3% of all reports, and deaths accounted for 2% of all reports. The concern for safety was reflected in prescriber survey results along with a recognition that LAIs can be helpful to target severe psychiatric symptoms and address treatment noncompliance. Conclusions: No randomized controlled studies were found. Identified published studies and reports were of low to very low quality. However, it appeared reasonable that the use of LAIs in a select group of pediatric patients can be helpful to target severe psychiatric symptoms and to enhance treatment compliance.

Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results.

Cabotegravir, an integrase strand transfer inhibitor, and rilpivirine, an NNRTI, constitute the first long-acting (LA), injectable, two-drug ART regimen approved for the maintenance of virological suppression in persons living with HIV-1 (PLHIV). The aim of this study was to assess clinical effectiveness and tolerability of LA cabotegravir/rilpivirine in a real-world setting. We conducted a retrospective, single centre study, including all PLHIV receiving LA cabotegravir/rilpivirine as standard-of-care in our tertiary centre even if initiated in clinical trials. Between 2014 and 2022, 126 PLHIV initiated LA cabotegravir/rilpivirine. All were ART-experienced, and 98.4% had a viral load (VL) of <50 copies/mL before LA cabotegravir/rilpivirine initiation. Median BMI at cabotegravir/rilpivirine initiation was 24 IQR (23-28). During a median follow-up of 9 months IQR (7-24), 27 patients discontinued cabotegravir/rilpivirine because of virological failure, 6 for adverse events, 11 for personal reasons unrelated to treatment tolerance and 5 for other reasons. Virological failure was not associated with a higher BMI, nor with weight gain during LA intramuscular (IM) cabotegravir/rilpivirine treatment, inadequate cabotegravir and rilpivirine concentrations, VL blips or the use of oral lead-in (OLI) or not. No drug resistance-associated mutation emerged. Adverse events leading to treatment interruption were injection-site pain (n = 3) and neuropsychological side effects (n = 3). A correlation between BMI and both cabotegravir and rilpivirine concentrations at 1 month post-initiation of LA-IM cabotegravir/rilpivirine was observed, with no impact of OLI. Data from this real-world cohort of PLHIV who received cabotegravir/rilpivirine LA injections suggest that this regimen is effective and well tolerated. Virological failures were not associated with the acquisition of resistance mutations.

The Langmuir-Blodgett trough (Langmuir film balance) can be used to understand the stabilizer concentrations in aqueous nano- and microsuspensions

Aqueous suspensions of poorly soluble, crystalline drug particles in the sub-micron range hold the ability to regulate the drug release for a defined period of time after e.g., intramuscular, or subcutaneous administration, working as an eminent formulation strategy for the preparation of long-acting injectables. Aqueous suspensions are typically prepared by top-down approaches, e.g., wet bead media milling or high-pressure homogenization, containing the active pharmaceutical compound and surfactants and/or polymers for stabilization purposes. Currently, the screening of proper stabilizers and adequate stabilizer concentration during formulation investigations is based on a trial-and-error approach with variations in combinations, concentrations, and/or ratios. To obtain a more efficient methodology during formulation screening, the present study investigated the correlation between the surface activity of two different surfactants, i.e., poloxamer 188 and polysorbate 20, by drop profile tensiometry and Langmuir trough monolayer, and the obtained sizes of cinnarizine particles as a tool to predict the optimal surfactant concentration to prepare physical stable nano- and microsuspensions. The obtained results demonstrated that the molecular area determined as the area per surfactant molecule measured in the Langmuir trough combined with the specific surface area of the prepared suspensions could be used to predict the suitable concentration of the surfactant based upon short-term stress stability data. The results further showed that higher concentrations of poloxamer 188 were necessary to stabilize the suspensions when compared to the needed concentration of polysorbate 20. In addition, it was observed that there was a need for a slightly higher surfactant concentration when the suspensions were milled with the smallest bead size of 0.5 mm instead of larger sizes of bead (0.8 and 1.0 mm), which could not be accounted for by differences in specific surface area.

Characterising the nature of psychiatric disorders and patterns of antipsychotic medications prescribed in a psychiatric ward in a public hospital in Tasmania.

We present an evaluation of antipsychotic prescribing in an inpatient psychiatry ward in Hobart, Tasmania, to establish pattern of use, alignment with other psychiatric wards orcentres and the recommendations in the Royal Australian and New Zealand College of Psychiatry Clinical Practice Guidelines, and to determine predictors of polypharmacy. A descriptive cross-sectional survey design was used. Data from 118 patients discharged from the Royal Hobart Hospital (RHH) Mental Health Inpatient Unit between 01/02/2021 to 01/08/2021 were evaluated. Antipsychotic polypharmacy (APP) was observed in 40% of patients. When low doses of adjunctive ('PRN') use of olanzapine and quetiapine were excluded, the APP proportion was 35%. APP was predicted by age and by a schizophrenia diagnosis. Long-acting injections (LAIs) were used in 46% of the patients. The most common LAI was risperidone (52%). Average daily dose of antipsychotic at the time of discharge was 529mg chlorpromazine (CPZ) equivalents. High dose antipsychotics (more than 1000mg CPZ equivalents per day) was observed in 13% of the patients. The observed prescribing practice is consistent with other clinical settings. Antipsychotic prescribing practice should, however, continue to be monitored to ensure adherence to best practice guidelines.

Stated preferences for long-acting injectable ART among mobile men living with HIV in Malawi: a qualitative study

Background: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV). Methods: We conducted a qualitative sub-study within two trials (ENGAGE and IDEaL) in 24 health facilities in Malawi that enrolled MLHIV &gt;15 years not on ART. We conducted in-depth interviews with a stratified random sample of participants who had taken oral ART and self-reported mobility (travel) during the 6-month study (&gt;1 trip of &gt;3 nights). Interviews described cabotegravir/rilpivirine and asked about clients’ stated preferences for LAI vs. oral ART and their reasoning. Interviews were translated, transcribed, coded in Atlas.ti, and analyzed using framework analysis. Results: We interviewed 29 mobile MLHIV from 1 July to 30 August 2022, median age 36 (IQR:31-41), mean 28 nights away in last six months (SD: 40). Nearly all participants (26/29) expressed a preference for LAI over daily oral ART because LAI would reduce the risks of forgetting to take pills and unwanted disclosure. Three men preferred oral ART primarily due to fear of side effects from a new medication. A few men reported they would change their preference if injection site reactions prevented them from working. Conclusion: Mobile MLHIV in Malawi with previous ART adherence challenges expressed strong stated preferences for LAI over daily oral ART. Further research is needed to understand implementation challenges and potential effectiveness of LAI among harder-to-reach populations.

Disability and Adverse Effects of Oral Versus Long-Acting Injectable Antipsychotics in Schizophrenia-Spectrum and Bipolar Disorder: A Comparison Based on Data-Driven Taxonomy.

Patients undergoing antipsychotic treatment for psychiatric disorders may experience challenges in functioning, either stemming from the severity of the illness or from the tolerability issues of prescribed medications. The aims of this cross-sectional study are to investigate the impact of adverse effects of antipsychotic drugs on patients' daily life functioning, comparing oral and long-acting injectable (LAI) antipsychotics, and further dividing antipsychotics by receptor-binding profiles based on recently defined data-driven taxonomy. This study involved patients with schizophrenia and bipolar spectrum disorders taking oral or LAI antipsychotics. Disability and functioning levels were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the adverse effects of medications were evaluated using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and its subscales. The total sample consisted of 126 participants with a diagnosis of schizophrenia-spectrum or bipolar disorder, and included 54 males and 72 females ranging from 18 to 78 years of age (mean45.1, standard deviation 14); 78 patients were taking oral antipsychotics and 48 were taking LAI antipsychotics, with subcategories of muscarinic (31), adrenergic/low dopamine (25), serotonergic/dopaminergic (23), dopaminergic (1), LAI muscarinic (15), LAI adrenergic (6), and LAI serotonergic/dopaminergic (25). The UKU total score for adverse effects showed significant correlations with WHODAS total score (ρ=0.475; p<0.001). Compared with oral antipsychotics, LAIs showed significantly lower scores in psychological (p=0.014), autonomic (p=0.008), other (p=0.004), and sexual adverse effects (p=0.008), as well as the UKU total score (p=0.002). The Kruskal-Wallis test showed a significant difference in adverse effects between LAI and oral muscarinic subgroups, with LAIs having lower scores compared with antipsychotics binding to muscarinic receptors (p=0.043). These findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies.

Mobile Delivery Program to Prevent Relapse and Improve Functioning in Patients With Psychiatric Diseases.

The term "revolving door patients" refers to those who are frequently rehospitalized for relapse. This phenomenon can be explained by a multitude of factors, including a lack of medical and/or social support. On the basis of a review of various modalities of psychiatric treatment, such as long-acting injectables, assisted outpatient treatment, and telehealth, it is clear that a major underlying issue among people with psychiatric diseases who lack insight into their mental and physical health is medication nonadherence. Therefore, we propose a mobile delivery program (MDP) in which health care professionals deliver medications and care to psychiatric patients in their own homes. The target patient population for MDP is patients with medication nonadherence, frequent emergency department visits, and missed appointments. Patients with mental illnesses, especially schizophrenia, are disproportionately represented among the homeless and incarcerated populations. By implementing MDP, we can help break the cycle of incarceration for patients with mental illnesses and homelessness. In addition, the cost of transportation and salaries for the mobile delivery team would be considerably lower than the billions of dollars spent each year due to relapses, emergency department visits, inpatient admissions, and crime leading to long-term stays in correctional facilities. This model has the potential to reduce relapse, improve functioning, and reduce excess morbidity and mortality. Substantial cost savings for health services can, in turn, be expected.

Utilizing long-acting injectables to address noncompliance among adolescents diagnosed with bipolar disorder.

Utilizing long-acting injectables to address noncompliance among adolescents diagnosed with bipolar disorder.

Novel dissolution methods for drug release testing of Long-Acting injectables

Long-acting parenteral drug products are a popular choice for therapeutic areas requiring long term treatment. These products range from dispersed systems such as drug suspensions and polymeric microspheres to in situ forming polymeric implants. The lack of reliable drug release testing methods for these drug products not only impedes the development of new drug products but also affects generic drug development. Current release methods suffer from a range of problems such as high variability, poor reproducibility, poor discriminatory ability, lack of depot-like structure formation (that could mimic the in vivo situation). Moreover, shorter duration (less than a week) of release renders them unsuitable for in vitro-in vivo correlations (IVIVCs). To overcome these issues, novel adapters were developed for both USP-type-II & IV apparatus. These adapters were validated and assessed using the long-acting injectable (LAI) suspension drug product Depo Provera 150® as well as its Q1/Q2 equivalents. For USP-type-IV apparatus, two open adapter designs (conical and ellipsoidal shaped cavity with volume capacities of 50 µl and 1 ml, respectively) were developed. A closed conical adapter design with a volume capacity of 0.05 ml was developed for USP apparatus type-II. All three novel adapter designs effectively retained the suspensions, achieved release durations of 3–6 weeks with good reproducibility, minimal variability (RSD≤5%) and had good discriminatory ability. Based on this, the adapter-based dissolution methods were deemed suitable for IVIVC development of long-acting injectables. A successful Level A IVIVC was developed for Depo SubQ Provera 104® and its Q1Q2 equivalents using USP apparatus type IV with a conical adapter design. The closed adapter design for apparatus type-II was also investigated for suitability with risperidone in situ forming implants. The adapter was able to securely retain and maintain the shape of the in situ forming implants and resulted in release profiles of up to one month with good discriminatory ability and low standard error (RSD≤5%). These novel adapters hold promise of wide use for in vitro release testing of different long-acting parenteral drug products.