Long-acting Injection Research Articles

Paliperidone long-acting injection in the treatment of an adolescent with schizophrenia with fluctuating mental symptoms during menstrual period: a case report.

The treatment of schizophrenia, a chronic disabling psychiatric disorder, mainly relies on antipsychotics to control the disease and improve clinical symptoms. Various medication options are available, and differences in treatment effects, even for the same medication, have been noted. Treatment efficacy is correlated with the patient's sex, age, and physical condition. When a drug fails to achieve the desired effect or the symptoms are unstable, the drug dose is often increased or a change in medication is advised according to the patient's situation. We report the case of a 16 years-old girl with schizophrenia and apparent psychotic symptoms. According to the genetic testing results, the symptoms were effectively controlled, and she was discharged from the hospital with the prescription of paliperidone sustained-release tablets. During the follow-up, her symptoms fluctuated during menstrual period, causing her great distress. Furthermore, her compliance gradually declined during the following 2 years of treatment, and the medication was often discontinued. We changed the drug from an oral tablet to an injection preparation while maintaining the active ingredients of the drug. The patient's symptoms were significantly controlled, and no fluctuation of symptoms occurred during the menstrual cycle. Long-acting antipsychotic injections can be administered to female adolescents with schizophrenia who experience fluctuating psychotic symptoms during menstruation. This technique can ensure both consistency of medication and improvement in clinical symptoms.

The Importance of Drug Delivery in the Clinical Development and Lifecycle of Drug Products with Examples from Authorised Medicinal Products

Drug delivery systems (DDS) are formulations or devices that enable the introduction of a therapeutic into the body and its delivery to its target site, potentially enhancing its efficacy and safety. Advances in formulation approaches related to the enhancement of solubility, permeability and thus bioavailability of drugs have already been successfully implemented by the pharmaceutical industry. This review highlights the importance of formulations/DDS in the clinical development and the lifecycle of drug products. Examples from already authorised drug products have been used to showcase how the development of appropriate formulations/DDS could deliver drugs to the site of action (e.g., pulmonary and nasal drug delivery) and enhance patient adherence to medication (e.g., long-acting injectables, 3D-printed tablets). Moreover, examples from authorised products have been provided to highlight how formulation can improve safety (e.g., liposomes, abuse-deterrent opioid formulations) and efficacy (e.g., albumin-based nanoparticles, permeation enhancers for oral delivery of peptides).

Does Slow and Steady Win the Race? Rates of Antipsychotic Discontinuation, Antipsychotic Dose, and Risk of Psychotic Relapse.

Antipsychotics are recommended for prevention of relapse in schizophrenia. It is unclear whether increased risk of relapse following antipsychotic discontinuation is predominantly associated with an absolute magnitude of dose reduction or rate of antipsychotic reduction. Establishing the responsible mechanism is important because prolonged withdrawal schedules have been suggested to reduce risk of relapse. Individual patient data from antipsychotic discontinuation studies were obtained. We estimated the occupancy of receptors over time using half-lives and median effective dose ED50 values obtained from pharmacokinetic and receptor occupancy studies. Hazard ratios for relapse events were calculated using Cox proportional hazards models to assess the influence of formulation (oral, 1-monthly, and 3-monthly injections). The change in hazard ratio over time was estimated, and the effect of time-varying covariates was calculated, including rate of occupancy reduction and absolute receptor occupancy. Five studies including 1388 participants with schizophrenia were identified (k = 2: oral, k = 2: 1-monthly injection, k = 1: 3-monthly injection). Withdrawal of long-acting injectable medication did not lead to a lower hazard ratio compared with withdrawal of oral medication, and this included the period immediately following randomization. Hazard ratios were not associated with the rate of decline of receptor occupancy; however, they were associated with reduced absolute occupancy in trials of long-acting injections (P = .038). Antipsychotic discontinuation is associated with an increased risk of psychotic relapse, related to receptor occupancy. Although relapse does not appear to be related to the rate of discontinuation, gradual discontinuation strategies may allow for easier antipsychotic reinstatement in case of symptomatic worsening.

Preferences of Patients and Providers in High-Burden Malaria Settings for Long-Acting Malaria Chemoprevention.

Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million infections each year. We sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation. We administered questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia. Questions explored preferences and concerns around long-acting antimalarial formulations compared with oral formulations. We recruited 202 patient respondents (Kenya, n = 102; Zambia, n = 100) and 215 provider respondents (Kenya, n = 105; Zambia, n = 110). Long-acting injection was preferred to oral pills, whereas oral pills were preferred to implant or transdermal administration by patient respondents. Of 202 patient respondents, 80% indicated that they 'definitely would try' malaria chemoprevention offered by injection instead of oral pills. Of parents or guardians, 84% of 113 responded that they 'definitely would' have their child age <12 years and 90% of 88 'definitely would' have their child ≥12 years receive an injection for malaria prevention. Provider respondents indicated that they would be more likely to prescribe a long-acting injectable product compared with an oral product for malaria chemoprevention in adults (70%), adolescents ages 12 years and older (67%), and children <12 years (81%). Potential for prolonged adverse effects with long-acting products was the highest concern for patient respondents, while higher medication-related cost was cited as the most concerning barrier to implementation by providers. Overall, these findings indicate enthusiasm for the development of long-acting injectable antimalarials to provide individual delivery method options across age groups.

Sociodemographic and clinical factors associated with prescription of first- versus second-generation long-acting antipsychotics in incarcerated adult males.

Information on patterns of prescription of long-acting injection (LAI) antipsychotics among people who are incarcerated is lacking. Therefore, we aimed to evaluate prescribing rates for first-generation antipsychotic (FGA)-LAI versus second-generation antipsychotic (SGA)-LAI and to identify the factors associated with the prescription of one of the two classes of LAI. A cross-sectional study was conducted among incarcerated adult males hosted in Monza detention center between January 2013 and April 2023. Socio-demographic and clinical data were retrospectively collected. Descriptive and univariate statistics as well as logistic regression analyses were performed. Data were available for 135 consecutive incarcerated adult males with different mental disorders who received a LAI as part of their treatment. 75.6% of our sample was treated with FGA-LAIs, with haloperidol as the most commonly prescribed drug, followed by zuclopentixol and aripiprazole. Diagnosis of bipolar disorder and concomitant administration of antidepressants were statistically significant predictors of SGA-LAI prescription. Some patients' characteristics may influence prescription patterns in prison. Further longitudinal studies with larger samples should confirm these findings.

Second International Consensus Study of Antipsychotic Dosing (ICSAD-2).

Expert consensus-based clinically equivalent dose estimates and dosing recommendations can provide valuable support for the use of drugs for psychosis in clinical practice and research. This second International Consensus Study of Antipsychotic Dosing provides dosing equivalencies and recommendations for newer drugs for psychosis and previously reported drugs with low consensus. We used a two-step Delphi survey process to establish and update consensus with a broad, international sample of clinical and research experts regarding 26 drug formulations to obtain dosing recommendations (start, target range, and maximum) and estimates of clinically equivalent doses for the treatment of schizophrenia. Reference agents for equivalent dose estimates were oral olanzapine 20 mg/day for 15 oral and 7 long-acting injectable (LAI) agents and intramuscular haloperidol 5 mg for 4 short-acting injectable (SAI) agents. We also provide a contemporary list of equivalency estimates and dosing recommendations for a total of 44 oral, 16 LAI, and 14 SAI drugs for psychosis. Survey participants (N = 72) from 24 countries provided equivalency estimates and dosing recommendations for oral, LAI, and SAI formulations. Consensus improved from survey stages I to II. The final consensus was highest for LAI formulations, intermediate for oral agents, and lowest for SAI formulations of drugs for psychosis. As randomized, controlled, fixed, multiple-dose trials to optimize the dosing of drugs for psychosis remain rare, expert consensus remains a useful alternative for estimating clinical dosing equivalents. The present findings can support clinical practice, guideline development, and research design and interpretation involving drugs for psychosis.

Cost-Effectiveness Analysis of Long-acting Injectable Once-monthly of Aripiprazole Compared with Long-acting Injectable Once-monthly Paliperidone Palmitate for the Treatment of Stable Schizophrenia Patients in Thailand

Objective: Long-acting injectable (LAI)-aripiprazole and LAI-paliperidone palmitate are both second-generation antipsychotics that have been introduced to increase drug compliance in patients. These attributes are expected to enhance drug compliance, particularly in stable patients. The previous studies demonstrated that the efficacy of LAI-aripiprazole and LAI-paliperidone palmitate is controversial. Nevertheless, the costs of treatments and adverse events of both LAI-aripiprazole and LAI-paliperidone palmitate are unlikeness. As there had been no previous cost-effectiveness studies comparing the use of LAI-aripiprazole and LAI-paliperidone palmitate in Thailand, this study was carried out to investigate the matter. Materials and Methods: This study analysed the cost-effectiveness of LAI-aripiprazole compared with LAI-paliperidone palmitate in the treatment of stable schizophrenia, by using the Markov model from a societal perspective. Results: The total cost of treatment with LAI-aripiprazole and LAI-paliperidone palmitate was 1,334,919.05 baht and 1,329,818.79 baht, respectively, while the quality-adjusted life years (QALYs) were both 16.35 years. Life-year of the treatment with LAI-aripiprazole and LAI-paliperidone was 24.27 years and 24.25 years, respectively. The cost-effectiveness ratios (CER) of the treatment with LAI-aripiprazole and LAI-paliperidone palmitate were 81,652.85 baht/QALY gained and 81,330.94 baht/QALY gained, respectively. Conclusion: In Thailand, the treatment of stable schizophrenia with LAI-aripiprazole was shown to provide similar benefits to LAI-paliperidone palmitate in terms of QALYs, despite being more costly. Comparatively, LAI-aripiprazole exhibited better clinical efficacy and led to a longer average life expectancy than LAI-paliperidone. Treatment with LAI-aripiprazole may be dominant strategy, especially with a 2% reduction in drug cost. The results could contribute to appropriate decision-making by policymakers.

Wet bead milling by dual centrifugation – An approach to obtain reproducible and differentiable suspensions

Aqueous nano- and microsuspensions containing poorly water-soluble, crystalline drug particles have in the recent years sparked an interest for the preparation of long-acting injectables (LAIs), which increase patient compliance for patients treated for long-term or chronic conditions. Nano- and microsuspensions are often prepared by top-down methods, such as wet bead milling, with the addition of stabilizers in the dispersion media, such as surfactants, which influence the particle sizes and physical stability of the suspension. To improve the efficacy of formulation screening for nano- and microsuspensions, dual centrifugation was utilized in this study whereby 40 samples could be manufactured simultaneously to support the formulation definition. Hence, the type and concentration of stabilizer as well as bead size and milling speed was investigated throughout the presented study, but also the ability of the method to produce consistent data was investigated. The obtained results demonstrated that the particle profile obtained after milling was very consistent from run to run and so was the observed stability data, i.e., running n = 1 experiment per combination could clearly be justified as a predictable approach for the formulation screening. The data also showed that the stabilizer, as well as its concentration highly influenced the physical stability of suspensions containing both the two investigated model compounds, i.e., both cinnarizine and indomethacin, where the biggest increase in particle sizes was observed within the first week. For short-term studies, polysorbate 20 was found to be a suitable stabilizer for suspensions of cinnarizine, whereas sodium dodecyl sulphate was more suitable for indomethacin suspensions immediately after the milling even with 1% (w/v) stabilizer solution, but not sufficient for short-term stability due to an insufficient stabilizer concentration. Smaller particles sizes could be achieved by milling the suspensions with the smallest bead sizes and at the highest speed of 1500 rpm without disrupting the crystal structure of the active pharmaceutical ingredient (API), which was confirmed by X-ray Powder Diffraction.

Constructing Antiretroviral Supramolecular Polymers as Long-Acting Injectables through Rational Design of Drug Amphiphiles with Alternating Antiretroviral-Based and Hydrophobic Residues.

One of the main challenges in the development of long-acting injectables for HIV treatment is the limited duration of drug release, which results in the need for frequent dosing and reduced patient adherence. In this context, we leverage the intrinsic reversible features of supramolecular polymers and their unique ability to form a three-dimensional network under physiological conditions to design a class of self-assembling drug amphiphiles (DAs) based upon lamivudine, a water-soluble antiretroviral (ARV) agent and nucleoside reverse transcriptase inhibitor. The designed ARV DAs contain three pairs of alternating hydrophobic valine (V) and hydrophilic lamivudine-modified lysine (K3TC) residues with a varying number of glutamic acids (E) placed on the C-terminus. Upon dissolution in deionized water, all three ARV DAs were found to spontaneously associate into supramolecular filaments of several micrometers in length, with varying levels of lateral stacking. Addition of 1× PBS triggered immediate gelation of the two ARV DAs with 2 or 3 E residues, and upon dilution in an in vitro setting, the dissociation from the supramolecular state to the monomeric state enabled a long-acting linear release of the ARV DAs. In vivo studies further confirmed their injectability, rapid in situ hydrogel formation, enhanced local retention, and long-acting therapeutic release over a month. Importantly, our pharmacokinetic studies suggest that the injected ARV supramolecular polymeric hydrogel was able to maintain a plasma concentration of lamivudine above its IC50 value for more than 40 days in mice and showed minimal systemic immunogenicity. We believe that these results shed important light on the rational design of long-acting injectables using the drug-based molecular assembly strategy, and the reported ARV supramolecular hydrogels hold great promise for improving HIV treatment outcomes.

Forensic psychiatry patients, services, and legislation in Nunavut and Greenland

Circumpolar regions face unique challenges in establishing and maintaining mental health care systems, including forensic psychiatry services. The scarcity of data and lack of evidence concerning the forensic psychiatry patient (FPP) populations of Nunavut and Greenland exacerbates the challenges of informing best practices and healthcare planning.By comparing the prevalence of forensic psychiatry patients, the mental health care services, and the legislation in these two relatively similar but unique regions, insight may be gained that can help inform healthcare planning.This cross-sectional study includes all forensic psychiatry in- and outpatients in one year from Nunavut (2018) and on February 29, 2020, in Greenland.The Greenland sample (n = 93) was nearly four times larger than the Nunavut sample (n = 15) at the population level. Despite considerable differences in forensic legislation and service supply, the forensic psychiatry patients in the two areas share several similarities. A total of 87% (n = 13) in the Nunavut sample were diagnosed with a DSM-5 schizophrenia spectrum disorder or other psychotic disorder. In Greenland, 82% (n = 76) were diagnosed with an ICD-10 F2 diagnosis (schizophrenia, schizotypal and delusional disorders). Approximately 2/3 of the patients in both populations were diagnosed with substance use disorder, and 60% of the Nunavut FPP received long-acting antipsychotic injections versus 62% in Greenland. Nearly half of the FPPs in both populations had never been convicted prior to entering the forensic psychiatry system; Nunavut 45% versus Greenland 47%. A substantial proportion of Greenlandic FPPs were outpatients compared to Nunavut (83% versus 47%).This study is an essential first step toward describing a Model of Care for forensic psychiatry patients in circumpolar regions; furthermore, the clinical similarities between the two populations provide support for future joint Arctic research and the inclusion of artic forensic patients in international studies.

Extrapyramidal adverse events and anticholinergics use after the long-term treatment of patients with schizophrenia with the new long-acting antipsychotic Risperidone ISM®: results from matching-adjusted indirect comparisons versus once-monthly formulations of Paliperidone palmitate and Aripiprazole monohydrate in 52-week studies

BackgroundRisperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting.MethodsA literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints.ResultsThe analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p < 0.001). Use of anticholinergic agents for the alleviation of EPS was also shown to be significantly lower in Risperidone ISM patients than in those receiving PP (OR [95% CI] 0.29 [0.10, 0.83], p = 0.021) or AOM (OR [95% CI] 0.01 [0.003, 0.06], p < 0.001), suggesting a superior tolerability profile for clinically relevant EPS. Results from the sensitivity analyses comparing stabilized and stable patients receiving Risperidone ISM to those receiving AOM yielded similarly favorable conclusions in line with the base case analyses.ConclusionsThis MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting.

Long-Acting Injectable Antipsychotic Treatment for Schizophrenia in Asian Population: A Scoping Review.

Evidence of comparative benefits of long-acting injectable (LAI) antipsychotics in Asian patients with schizophrenia has been inconsistent. This scoping review aimed to synthesize the current evidence in the past ten years and provide an overview of efficacy, safety, treatment adherence, patient attitudes, and healthcare resource utilization of LAI in this population. A systematic search was conducted with a pre-defined search strategy in six electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, CINAHL, and PsycArticles. A total of 46 studies were included, including 15 cohort studies, 13 single-arm trials, 10 randomized controlled trials, four mirror-image studies, three cross-sectional studies, and one controlled clinical trial. Paliperidone palmitate once-monthly injection (27/46) and risperidone LAI (14/46) were the most frequently investigated LAIs. Compared with oral antipsychotic medications (OAMs), LAIs demonstrated a lower rate of relapse/hospitalization and comparable improvement in efficacy. Adverse events (AEs) were similar between LAIs and OAMs, although types and incidence varied. Significant reduction in the length of hospitalization and number of outpatient visits/inpatient admission was observed after initiation of LAIs. These findings suggest that LAI demonstrated comparable efficacy and safety among Asian populations with schizophrenia in comparison to OAMs. Better adherence and lower relapse were observed in patients receiving LAIs from published evidence. Future research is warranted to better understand the comprehensive performance of LAI in specific population or context.

Association of Long-acting Injectable Antipsychotics with Inpatient Seclusion and Restraint Events at a Public Psychiatric Hospital

Objective: Seclusion and restraint (S/R) are emergency safety measures to manage aggressive behaviour and prevent physical harm to self and others during psychiatric hospitalisations. Antipsychotics have been reported to reduce the incidence of S/R events during psychiatric hospitalisation. This study explores factors associated with inpatient S/R events and investigates whether long-acting injectable (LAI) antipsychotic prescription is associated with a reduction of S/R events. Method: Data on the number of S/R events during hospital stay were collected from the medical records of 741 psychiatric inpatients admitted between 2012 and 2017, and categorised into groups of 0, 1–2 and recurrent (≥3) S/R. Multinomial logistic regression analysis was performed to find the association between S/R events and several demographic and clinical variables, including the time to initiation of LAI (TLAI). Results: TLAI was not significantly associated with S/R events. Antipsychotic medication prescription was associated with a decreased risk of recurrent S/R events (OR = 0.47; 95% Cl = 0.24–0.92), however, it was not significant for the group having 1–2 S/R events (OR = 0.74; 95% Cl = 0.37–1.49). Individuals with recurrent S/R events were more likely to have forensic admission, transfer from jail or supervised facility, higher psychiatric comorbidity, and higher inpatient medications and prescription changes. Conclusion: Early initiation of LAI antipsychotics was not associated with S/R events; however, routine oral antipsychotic medication prescription was associated with decreased risk of S/R events. Specific predictors of S/R episodes may be used in preventative efforts aimed at decreasing S/R events.

Cumulative Clinical Experience of the Use of Paliperidone Palmitate 3-Monthly Long-Acting Injection in the Treatment of Schizophrenia: A Critical Appraisal.

Paliperidone palmitate 3-monthly (PP3M), an approved maintenance treatment for patients with schizophrenia, was the first long-acting antipsychotic injectable (LAI) to require only four administrations per year. Here, we aimed to review the available evidence about its use in the management of schizophrenia to date and highlight key study findings in order to provide a balanced overview of current experience in clinical practice. For that purpose, an extensive search of available literature from PubMed, Embase, and Web of Science was conducted in March 2023. Emerging data from real-world studies appear to signal that the benefits of the use of PP3M may well extent beyond the obvious convenience for patients and resource efficiency for services and may be actually associated with improved effectiveness and patient satisfaction. Large naturalistic studies from Australia, Europe and the US comparing treatment continuation between newer LAIs and/or oral antipsychotics showed that patients treated with PP3M had higher compliance rates and a longer period of continuous use. The risk of relapse, re-hospitalization and number of bed days was also lower with PP3M compared to PP1M and other LAIs as demonstrated by several cohort studies. Furthermore, patients treated with PP3M were using lower doses of benzodiazepines and concomitant oral antipsychotics compared with other LAIs. What is more, PP3M appears to positively impact patients' satisfaction and quality of life, facilitating long-term goals. In fact, recent studies recorded better quality-adjusted life years and decreased stigma, with improved social acceptability and promotion of rehabilitation for patients transitioning to PP3M. The rates of general satisfaction rates with PP3M were also higher among psychiatrists and caregivers who reported overall less concerns. In conclusion, clinical exposure and a growing body of evidence thus far, reinforce the use of PP3M in an effort to enhance patient outcomes alongside individual experience and treatment persistence.

Hot Melt Extrusion as a Formulation Method of Terpolymer Rods with Aripiprazole: A Preliminary Study

Aripiprazole (ARP) is an atypical neuroleptic used in the therapy of mental diseases such as schizophrenia. The lack of optimal adherence to an oral therapy regime creates the basis for designing ARP long-acting injections. This study aimed to use 105 °C hot melt extrusion (HME) as a formulation method for rods based on poly(d,l-lactide-co-glycolide-co-trimethylene carbonate) with a molecular weight (Mn) of 21 kDa (Td,l 21), poly(l-lactide-co-glycolide-co-trimethylene carbonate) with a Mn of 59 kDa (Tl 59), and with a Mn of 77 kDa (Tl 77). The following methods were involved in the research: NMR, DSC, XRD, HSM, FTIR, GPC, SEM, and mechanical tests. HME at 105 °C (i) ensured flow behavior for terpolymers, (ii) did not influence the terpolymers’ composition and (iii) the polymorph changes of ARP, and (iv) resulted in the changes in terpolymers’ Mn. For the rods with ARP based on Td,l 21 (Td,l 21 rod-ARP) and Tl 59 (Tl 59 rod-ARP), plasticization was noted. No drug–terpolymer interactions were revealed. No pores were observed on the surface. Due to its high flexibility and rubber character, Td,l 21 rod-ARP may be proposed for intramuscular administration, whereas Tl 59 rod-ARP, due to its higher strength and moderate stiffness, is proposed for subcutaneous administration.

Projecting the Potential Budget Impact Analysis of Paliperidone Palmitate in Egyptian Adult Patients with Schizophrenia.

Background: Schizophrenia is a serious mental disorder that has greater negative consequences on role functioning than many other severe chronic diseases. Objective: We evaluated the economic impact of long-acting injections of paliperidone palmitate (PP) vs daily oral antipsychotics to treat chronic schizophrenia from a societal perspective over a 2-year period. Methods: A static budget impact model was developed to compare PP with daily oral antipsychotics (risperidone, olanzapine, and aripiprazole) in the treatment of patients with chronic schizophrenia. Our study included treatments used during relapse and hospitalization, validated by an expert panel. The clinical parameters were extracted from the PRIDE trial. Direct medical costs and indirect costs were measured. The unit cost of drug acquisition for all medications was extracted from the public sector. One-way sensitivity analyses were conducted. Results: The target population in our model was estimated to be 142 incident patients. In the first year, the total drug costs in Egyptian pounds (EGP) for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5.6 million, respectively. In the second year, the total drug costs for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5 million, respectively. The total costs for PP (£11.6 million) over 2 years were less than those of oral antipsychotics without PP (£12.7 million). PP produced an estimated budget savings of £1 046 561 (budget savings per patient per year, £3667). In addition, PP resulted in the avoidance of 18 hospitalizations per year compared with the without-PP arm. Sensitivity analyses showed that the percent of hospitalizations for both oral antipsychotics and PP had the greatest impact on the results. Conclusion: The lower hospitalization rates associated with PP offset the increase in drug costs. PP may potentially be cost-saving compared with the standard of care in chronic schizophrenia in Egyptian representative healthcare settings. Policy makers may consider this approach to improve patient outcomes and budget sustainability.

Lsisi G, Ezzat M, Ramadan M. Projecting the Potential Budget Impact Analysis of Paliperidone Palmitate in Egyptian Adult Patients with Schizophrenia

Background: Schizophrenia is a serious mental disorder that has greater negative consequences on role functioning than many other severe chronic diseases. Objective: We evaluated the economic impact of long-acting injections of paliperidone palmitate (PP) vs daily oral antipsychotics to treat chronic schizophrenia from a societal perspective over a 2-year period. Methods: A static budget impact model was developed to compare PP with daily oral antipsychotics (risperidone, olanzapine, and aripiprazole) in the treatment of patients with chronic schizophrenia. Our study included treatments used during relapse and hospitalization, validated by an expert panel. The clinical parameters were extracted from the PRIDE trial. Direct medical costs and indirect costs were measured. The unit cost of drug acquisition for all medications was extracted from the public sector. One-way sensitivity analyses were conducted. Results: The target population in our model was estimated to be 142 incident patients. In the first year, the total drug costs in Egyptian pounds (EGP) for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5.6 million, respectively. In the second year, the total drug costs for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5 million, respectively. The total costs for PP (£11.6 million) over 2 years were less than those of oral antipsychotics without PP (£12.7 million). PP produced an estimated budget savings of £1 046 561 (budget savings per patient per year, £3667). In addition, PP resulted in the avoidance of 18 hospitalizations per year compared with the without-PP arm. Sensitivity analyses showed that the percent of hospitalizations for both oral antipsychotics and PP had the greatest impact on the results. Conclusion: The lower hospitalization rates associated with PP offset the increase in drug costs. PP may potentially be cost-saving compared with the standard of care in chronic schizophrenia in Egyptian representative healthcare settings. Policy makers may consider this approach to improve patient outcomes and budget sustainability.

The first nano-cocrystal formulation of marine drug cytarabine with uracil based on cocrystal nanonization strategy for long-acting injection exhibiting enhanced antitumor activity

To emphasize the superiority of uracil (UR) in ameliorating biopharmaceutical characteristics of marine antitumor medicine cytarabine (ARA), thus gaining some innovative opinions for the exploitation of nanococrystal formulation, a cocrystal nanonization strategy is proposed by integrating cocrystallization and nanosize preparation techniques. For one thing, based on UR's unique structural features and natures together with advantages of preferential uptake by tumor cells, cocrystallizing ARA with UR is expected to improve the in vitro/vivo performances. For another, the nanonization procedure is oriented towards maintaining the long-term effective drug level. Along this route, a cocrystal of ARA with UR, viz., ARA-UR, is successfully synthesized and then transformed into nano-cocrystal. The cocrystal structure is precisely confirmed by various methods, demonstrating that a 1:1 ARA and UR in the crystal forms cytosine-UR hydrogen-bonding interactions, thus constructing supramolecular frameworks by strong π-π stacking interplays; while the nano-cocrystal is block-shaped particles of 562.70 nm with zeta potential −33.40 mV. The properties of cocrystal ARA-UR and its nano-cocrystal in vitro/vivo are comparatively explored by theoretical calculations and experimental analyses, revealing that permeability of both is significantly increased than ARA per se. Notably, the meliorative natures of both the cocrystal and nano-cocrystal in vitro bring excellent antitumor activity, but the latter has greater strengths over the former. More notably, the nano-cocrystal can sustain effective concentration for a relatively longer time, causing lengthened retention time and better absorption in vivo. The contribution offers a fire-new dosage form of ARA for long-lasting delivery, thus filling the vacancy in nanococrystal studies about marine drugs.

Clozapine in Combination With Olanzapine Long-Acting Injection: The Intersection of Treatment-Resistant Schizophrenia and Poor Medication Adherence-A Case Report.

Clozapine in Combination With Olanzapine Long-Acting Injection: The Intersection of Treatment-Resistant Schizophrenia and Poor Medication Adherence-A Case Report.

Cost-utility analysis of using paliperidone palmitate in schizophrenia in China.

Objective: Long-acting injections (LAIs) of paliperidone palmitate have been shown to improve medication adherence and relieve psychotic symptoms. However, the specific cost-utility analysis of these LAIs in schizophrenia in China remains unclear. Methods: A multi-state Markov model was constructed to simulate the economic outcomes of patients with schizophrenia in China who received paliperidone palmitate 1-month formulation (PP1M), paliperidone palmitate 3-month formulation (PP3M), and paliperidone extended-release (ER). A cost-utility analysis was conducted, mostly derived from published literature and clinical databases. All costs and utilities were discounted at a rate of 5% per annum. The primary outcome measure was the incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were also applied. Results: After 20years, compared to ER, using PP1M resulted in an increased discounted cost from $36,252.59 to $43,207.28. This increased cost was associated with a gain in quality-adjusted life years (QALYs) from 8.60 to 9.45. As a result, the ICER for PP1M was estimated to be $8,247.46/QALY, which was lower than the willingness-to-pay (WTP) threshold of $12,756.55/QALY. When using PP3M instead of ER, the incremental cost was $768.81 and the incremental utility was 0.88 QALYs, projecting an ICER of $873.13/QALY, which was also lower than the WTP threshold of $12,756.55/QALY. The univariate sensitivity analysis showed that the costs of PP1M, PP3M, and ER had the greatest impact on ICERs. The probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,756.55/QALY, the probability of PP1M and PP3M being cost-effective was 59.2% and 66.0%, respectively. Conclusion: From the Chinese healthcare system perspective, PP3M and PP1M are both more cost-effective compared to ER, and PP3M has notable cost-utility advantages over PP1M.