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Introduction: Studies evaluating patient and healthcare professional (HCP) preferences regarding long-acting injectable (LAI) antipsychotic agent attributes are lacking., Methods: Surveys were administered to physicians, nurses, and patients who had at least two experiences with TV-46000, an investigational subcutaneous LAI antipsychotic agent for the treatment of schizophrenia, as part of the SHINE study (NCT03893825). Survey topics included preferences for route of administration, potential LAI dosing intervals (once-weekly, twice a month, once a month [q1m], every 2 months [q2m]), injection location, ease of use, syringe type, needle length, and need for reconstitution., Results: Patients (n = 63) had a mean (SD) age of 35.6 (9.6) years, age at diagnosis of 18 (10) years, and were mostly male (75%). There were 49 HCPs: 24 physicians and 25 nurses. Patients rated "a short needle" (68%), a "choice of [q1m or q2m] dosing interval" (59%), and "injection instead of oral tablet" (59%) as the most important features. HCPs rated "single injection to initiate treatment" (61%), "flexible dosing interval" (84%), and "injection instead of oral tablet" (59%) as the most important features. Subcutaneous injections were rated "easy to [receive/administer]" by 62% of patients and 84% of HCPs. When choosing between subcutaneous injections and intramuscular injections, 65% of HCPs preferred subcutaneous injections and 57% of patients preferred intramuscular injections. It was important to most HCPs to have four dose strength options (78%), a prefilled syringe (96%), and no need for reconstitution (90%)., Conclusions: Patients had a range of responses, and on some issues patient and HCP preferences differed. Altogether, this suggests the importance of providing patients with a range of options and the importance of patient-HCP discussions on treatment preference for LAIs., (© 2023. The Author(s).)

There is a growing number of protein drugs, yet their limited oral bioavailability requires that patients receive frequent, high dose injections. In situ forming implants (ISFIs) for controlled release of biotherapeutics have the potential to greatly reduce the injection frequency and improve patient compliance. However, protein release from ISFIs is a challenge due to their proclivity for instability. Specifically, factors such as the acidic microclimate within ISFIs can lead to protein aggregation and denaturation. Basic salts have been shown in PLGA microparticle and microcylinder formulations to significantly reduce protein instability by neutralizing this acidic environment. The overall objective of the study was to demonstrate that basic salts can be used with an ISFI system to neutralize the implant acidification. To this end, the basic salts MgCO3 and Mg(OH)2 were added to a protein-releasing ISFI and the effect on drug release, pH, implant swelling, implant diffusivity, and implant erosion were evaluated. Either salt added at 3 wt% neutralized the acidic environment surrounding the implants, keeping the pH at 6.64 ± 0.03 (MgCO 3 ) and 6.46 ± 0.11 (Mg(OH) 2 ) after 28 day compared to 3.72 ± 0.05 with no salts added. The salts initially increased solution uptake into the implants but delayed implant degradation and erosion. The 3 wt% Mg(OH) 2 formulation also showed slightly improved drug release with a lower burst and increased slope. We showed that salt additives can be an effective way to modulate the pH in the ISFI environment, which can improve protein stability and ultimately improve the capacity of ISFIs for delivering pH-sensitive biomolecules. Such a platform represents a low-cost method of improving overall patient compliance and reducing the overall healthcare burden., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians' decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: This retrospective longitudinal cohort study aimed to compare treatment patterns, healthcare resource utilization (HRU), and costs in patients with schizophrenia treated with second-generation antipsychotic long-acting injectables (SGA-LAIs): biweekly risperidone LAI versus once-monthly paliperidone palmitate.Methods: Patients who initiated risperidone LAI or paliperidone palmitate between 1 July 2007 and 31 December 2012 (index date) were identified from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid Multi-State insurance databases. Outcomes were assessed 12 months after the index date. Propensity score matching (1:1) based on patients' demographics and comorbidities was conducted. Outcome differences between the two cohorts were evaluated using t-tests for continuous variables, chi-square tests for categorical variables, and Wilcoxon rank-sum tests for count and cost variables. Regression models estimated the difference in medication use and adherence, likelihood of HRU, number of HRU events, and healthcare costs when comparing risperidone LAI versus paliperidone palmitate, while further adjusting for patient characteristics and pre-index HRU.Results: Patient characteristics were well balanced between the two cohorts (n = 499 each). Significantly lower discontinuation rates (36.5% vs. 53.3%; p < 0.001) and longer days of LAI coverage (233.6 vs. 131.7 days; p < 0.001) were observed in the paliperidone palmitate cohort versus the risperidone LAI cohort, respectively. Patients treated with paliperidone palmitate were 12.5 (95% confidence interval [CI]: 9.0-17.8) and 11.7 (95% CI: 8.0-17.4) times more likely to be adherent based on medication possession ratio and proportion of days covered, respectively (p < 0.001). Patients treated with paliperidone palmitate had reduced likelihood of hospitalization (adjusted odds ratio [95% CI]: 0.72 [0.55-0.95]), fewer emergency department (ED) visits (adjusted incidence rate ratio [aIRR]: 0.67 [0.61-0.73]) and reduced length of inpatient stay (aIRR: 0.86 [0.82-0.90]), which resulted in lower monthly inpatient hospitalization costs (-$77.58; p = 0.038) and ED visits (-$9.77; p = 0.021) relative to risperidone LAI.Limitations: Pharmacy costs were derived from health plan payment in the claims data and do not account for any discounts or rebates. This may have overestimated the branded drug costs in this analysis.Conclusions: These findings highlight the value of once-monthly paliperidone palmitate in the treatment of patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Clozapine is a second-generation antipsychotic typically reserved for refractory psychotic disorders due to its high-risk side effect profile to include agranulocytosis, with its attendant need for regular blood draws. While reports of extrapyramidal symptoms (EPS), including acute dystonic reactions, are exceedingly rare, we present the case of a 44-year-old male with a long-standing history of treatment-resistant schizoaffective disorder and no history of EPS who experienced an acute buccal dystonic reaction in the setting of clozapine initiation and discontinuation of depot and oral risperidone. This case report presents one of the few documented episodes of acute dystonic reactions occurring in the setting of clozapine administration. Based upon the patient's history and the dosing time line of the medications, we propose that an interaction between the clozapine and residual risperidone was responsible for the development of the acute buccal dystonia. [ABSTRACT FROM AUTHOR]

The present study evaluates the preparation of risperidone controlled release microspheres as appropriate long-acting injectable formulations based on a series of novel biodegradable and biocompatible poly(lactic acid)–poly(propylene adipate) (PLA/PPAd) polymer blends. Initially, PPAd was synthesized using a two-stage melt polycondensation method (esterification and polycondensation) and characterized by 1H-NMR, differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD) analyses. DSC and XRD results for PLA/PPAd blends (prepared by the solvent evaporation method) showed that these are immiscible, while enzymatic hydrolysis studies performed at 37 °C showed increased mass loss for PPAd compared to PLA. Risperidone-polyester microparticles prepared by the oil–water emulsification/solvent evaporation method showed smooth spherical surface with particle sizes from 1 to 15 μm. DSC, XRD, and Fourier-transformed infrared (FTIR) analyses showed that the active pharmaceutical ingredient (API) was dispersed in the amorphous phase within the polymer matrices, whereas in vitro drug release studies showed risperidone controlled release rates in all PLA/PPAd blend formulations. Finally, statistical moment analysis showed that polyester hydrolysis had a major impact on API release kinetics, while in PLA/PPAd blends with high PLA content, drug release was mainly controlled by diffusion.

Purpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M)., Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan-Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as -10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated., Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of -4.9% (95% CI: -9.2%, -0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs., Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified., Competing Interests: Cesar Giron-Hernandez is an employee of Janssen-Cilag and hold stocks and stock options, Joong Hee Hanc is an employee of Janssen Research & Development, LLC, USA and hold stocks and stock options. Roberta Alberio is an employee of Janssen-Cilag and hold stocks and stock options. Arun Singh is an employee of Janssen Research & Development, LLC, USA and hold stocks and stock options. Maria Paz García-Portilla has been a consultant to and/or received honoraria/grants from Alter, Alianza, Cassen-Recordati, Otsuka-Lundbeck, Angelini, Idorsia, Janssen-Cilag, Lundbeck, Otsuka, and SAGE Therapeutics. Maurizio Pompili has received lecture or advisory board honoraria or engaged in clinical trial activities with Angelini, Janssen, Lundbeck, MSD, Pfizer, and Recordati. Karl Knight is an employee of Janssen Research & Development, LLC, USA and hold stocks and stock options. Ute Richarz is an employee of Janssen-Cilag and hold stocks and stock options. Srihari Gopal was employed by Janssen Research & Development, LLC, USA when the study was conducted and is now employed by Regeneron. José Antunes is an employee of Janssen-Cilag and hold stocks and stock options. The authors report no other conflicts of interest in this work., (© 2023 Giron‐Hernandez et al.)

Introduction: Long-acting injectable antipsychotics (LAIs) have proven to be effective in the maintenance treatment of patients suffering from schizophrenia, and their safety and tolerability profiles represent a key factor in their long-term use and choice in clinical practice. Paliperidone palmitate (PP) is the only second-generation LAI (SGA-LAI), available in both one- (PP1M) and 3-month (PP3M) formulations. However, real-world prospective studies on PP1M and PP3M are still few and mostly conducted on small samples. In this context, we aimed to better define the safety and tolerability profile of PP using real world pharmacovigilance data., Methods: We retrospectively analyzed the publicly available data regarding Individual Case Safety Reports (ICSRs), presenting PP1M and/or PP3M as suspected drugs, reported on EUDRAVigilance between 2011 and June 30th, 2022. ICSRs relative to at least one SGA-LAI other than PP, reported between 2003 and June 30th, 2022, were also examined as reference group. Data were evaluated with a descriptive analysis, and then, as disproportionality measures, crude reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated., Results: A total of 8,152 ICSRs met the inclusion criteria, of those 77.7% ( n = 6,332) presented as suspected drug PP1M, 21.2% ( n = 1,731) PP3M, while 89 cases indicated both PP1M and PP3M. Significantly higher probabilities of reporting in PP-related reports were observed for the primary Standardized MedDRA Queries "Sexual Dysfunctions" (ROR = 1.45; 95% CI 1.23-1.70), "Haemodynamic oedema, effusions and fluid overload" (ROR = 1.42; 1.18-1.70), as well as "Fertility disorders" (ROR = 2.69; 1.51-4.80)., Discussion: Our analysis indicates that the tolerability and safety profiles of PP are in line with what is known for the other SGA-LAIs. However, differences regarding endocrine system ADRs have been noticed. The results presented in this work do not discourage the prescription of SGA-LAI formulations but aim to enhance their safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cicala, de Filippis, Barbieri, Cutroneo, De Fazio, Schoretsanitis and Spina.)

Purpose: The aim of this study was to assess the efficacy and safety of paliperidone palmitate (PP) treatment compared with risperidone long-acting injectable (LAI) treatments for patients with schizophrenia., Patients and Methods: Data mining was conducted in April 2022 across PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and PsycINFO. All published randomized controlled trials (RCTs) that assessed the effect of PP treatment for patients with schizophrenia when compared with the risperidone-LAIAs group were included. Relevant data were extracted and synthesized narratively. Results were expressed as standardized mean differences (SMDs) or risk ratios (RRs), with 95% confidence intervals (CIs)., Results: Four RCTs with 2451 patients met all the inclusion and exclusion criteria. Efficacy analyses showed no significant statistical differences in Positive and Negative Syndrome Scale (PANSS) total score changes at the endpoint (SMD = 0.10, P = 0.19), or in response rates (RR = 0.93; P = 0.40). Regarding the safety outcomes, PP treatment showed significantly increased risks of discontinuation rates for any reason (35.7% vs 30.4%; RR = 1.19; 95% CI, 1.03 to 1.39; P = 0.02) and nonsignificantly increased risks of total treatment emergent adverse events (TEAEs) (66.6% vs.64.8%; RR = 1.01; 95% CI, 0.94 to 1.09; P = 0.78) compared with the risperidone-LAIAs-treated group. Furthermore, PP may significantly increase total discontinuation rates compared with risperidone-LAIAs., Conclusion: Our meta-analysis did not find a more beneficial effect of PP compared to risperidone-LAIAs treatments for schizophrenia. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of randomized controlled trials and patients., Competing Interests: The authors declare that they have no competing interests in this work., (© 2023 Zhao et al.)

Introduction: Long-acting injectable (LAI) formulations of second-generation antipsychotics (SGA) are a mainstay in the treatment of schizophrenia-spectrum patients, and their use improves adherence and reduces relapse risk. Personalizing LAI-based therapy involves tailoring the transition from oral to LAIs based on individual and drug-related pharmacokinetic peculiarities., Areas Covered: We discuss pharmacokinetic considerations as a cornerstone of a smooth transition from oral to LAI SGAs based on works identified using an updated search in PubMed and Embase in February 2023. Establishing the extent of antipsychotic exposure during oral SGA-treatment from the patient's SGA levels is often a more appropriate orientation method to choose the equivalent LAI dose than population-based data. Oral dose adjustment during LAI transition can also be guided by checking SGA levels before the LAI injection., Expert Opinion: LAI SGAs may dominate the maintenance treatment of schizophrenia-spectrum disorders with increased use for other severe mental illnesses such as bipolar disorder. Spurring this trend is the development of newer formulations with longer injection intervals and increased administration ease, but transitioning from oral SGA remains a challenge. By understanding the pharmacokinetics of LAI formulations and measuring SGA levels during oral therapy, one can personalize/optimize the switch from oral SGAs to LAI counterparts.

We hypothesized that shifting from oral second-generation antipsychotics (SGA) to their long-acting injectable (LAI) counterpart would be beneficial for the psychopathological, cognitive, social, and general health domains in outpatients suffering from schizophrenia. We aimed to evaluate the prospective usefulness of SGA-LAI treatment by carrying out a head-to-head comparison of two different medications (i.e., aripiprazole monohydrate (Ari-LAI) and paliperidone palmitate 1 and 3 month (PP1M, PP3M)) in a real-world setting, assessing the effectiveness and tolerability of Ari-LAI and PP1M/PP3M over a 15 month follow-up. A total of 69 consecutive individuals affected by schizophrenia were screened for eligibility. Finally, 46 outpatients (29 treated with Ari-LAI, 13 with PP1M, and four with PP3M) were evaluated through clinical, functional, and neuropsychological assessment administrated at baseline and after 3-, 12-, and 15-month follow-up periods. Moreover, periodic general medical evaluations were carried out. We estimated an overall improvement over time on the explored outcomes, without differences with respect to the type of LAI investigated, and with a global 16.4% dropout rate. Our findings suggest that switching from oral SGA to SGA-LAIs represents a valid and effective treatment strategy, with significant improvements on psychopathological, cognitive, social, and clinical variables for patients suffering from schizophrenia, regardless of the type of molecule chosen.

Background: Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada., Methods: Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression - Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population., Results: Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration., Conclusions: AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms., Trial Registration: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N., (© 2023. The Author(s).)

Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2-3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic)., Competing Interests: John M. Kane has been a consultant for or received honoraria from Alkermes, Allergan, Boehringer-Ingelheim, Cerevel, Dainippon Sumitomo, HLS, Indivior, Intra-Cellular Therapies, Janssen, Johnson and Johnson, Karuna, LB Pharmaceuticals, Lundbeck, Lyndra, Merck, Minerva, Neurocrine Biosciences, Newron, Novartis, Otsuka, Pierre Fabre, Reviva, Roche, Saladex, Sunovion, Takeda, and Teva Pharmaceutical Industries; has received grant support from Otsuka, Lundbeck, Sunovion, and Janssen; and is a shareholder of LB Pharmaceuticals, North Shore Therapeutics, MedinCell, and Vanguard Research Group; royalties from Up to Date. Srihari Gopal was employed by Janssen Research & Development, LLC, USA when the study was conducted and is now employed by Regeneron Pharmaceuticals. All other authors are employees of Janssen and may hold company stocks or stock options. The authors report no other conflicts of interest in this work., (© 2023 Milz et al.)

Objective: Review the pharmacology, pharmacokinetics, efficacy, safety, and role of long-acting injectable cabotegravir (CAB-LA) in HIV preexposure prophylaxis (PrEP)., Data Sources: A literature search was performed using PubMed and Google Scholar (2012 to April 2022) with the search terms cabotegravir, preexposure prophylaxis, and PrEP. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, prescribing information, and review articles., Study Selection and Data Extraction: All English-language articles of studies assessing the efficacy and safety of CAB-LA for PrEP were included., Data Synthesis: CAB-LA is the first long-acting injectable therapy approved for HIV-1 PrEP in both men and women. It is a suspension given intramuscularly every other month. CAB-LA has been shown to be more effective than daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals. Two phase 3 trials were stopped early on the basis of superior efficacy of CAB-LA. The most common adverse effects were injection site reactions (ISRs), although they tended to decrease over time, and few participants in clinical trials discontinued use due to ISRs., Relevance to Patient Care and Clinical Practice: CAB-LA may be particularly useful for individuals with known adherence problems to oral therapy, those with renal impairment, and those with decreased bone mineral density. However, CAB-LA is more expensive than generic TDF/FTC and may be associated with weight gain., Conclusions: CAB-LA is the first long-acting injectable agent for HIV PrEP. It is more effective than oral TDF/FTC, is well-tolerated aside from ISRs, and has few clinically significant drug-drug interactions.

Objectives: Aripiprazole is an antipsychotic with a partial agonism of dopamine D 2 and D 3 receptors. This differential mechanism implies a rigorous appraisal of the appropriate therapeutic strategies in certain situations. To answer currently unsolved clinical questions about the use of oral and long-acting injectable (LAI) aripiprazole, we present here an expert consensus from 12 Spanish psychiatrists and a pharmacologist with extensive experience in the use of this antipsychotic., Methods: Through one face-to-face session and online collaboration, we reached consensus and established practical recommendations based on scientific evidence and clinical experience. We classified the available scientific literature according to SIGN system and attributed a level of evidence to each reviewed article., Results: The recommendations were divided according to (i) chronological dimension (based on previous treatments, including patients naïve or not to antipsychotic treatment and maintenance regimen), and (ii) dimension related to therapeutic options, comprising switches to aripiprazole and the most used combinations with this antipsychotic., Conclusions: We recommend considering aripiprazole as first treatment option in the early stages of schizophrenia and in patients with affective symptoms and contemplating a switch to aripiprazole LAI in all candidate patients. Importantly, switches from other antipsychotics should consider previous antipsychotic history and exposure to aripiprazole. KEYPOINTSAripiprazole can be considered as first treatment option in early stages of schizophrenia and in patients with significant affective symptoms.Aripiprazole LAI shows better adherence than oral aripiprazole and could be considered in all candidate patients.Before switching to aripiprazole, detailed information about previous antipsychotic history should be gathered.Switch to aripiprazole should be managed differently for aripiprazole naïve and non-naïve patients.Rigorous and controlled studies on antipsychotics in real clinical practice should be carried out.

Objective: This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients., Methods: This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics-Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years' duration of the illness., Results: Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group., Conclusion: High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent- onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

In this study, we present an innovative and facile in situ approach for extemporaneous preparation of sterile microparticles. An amazingly simple approach, in situ technology circumvents the stability, and scale up challenges as well as sterilization issues associated with long-acting particulate systems. Monophasic preconcentrates of donepezil base (DPZ), a model drug with a biodegradable polymer poly (DL-lactide-co-glycolide) (PLGA), with stabilizer were prepared by simple solution and sterilized by filtration (0.22 micron). The sterile preconcentrates when added to aqueous dextrose solution (total volume < 3 mL) generated ready-to-inject DPZ PLGA microparticles (DPZ-PLGA-MP) with high reproducibility, entrapment efficiency (> 80%), and size ~ 80 micron. DPZ micro suspension (DPZ-MS) with high precipitation efficiency (> 90%) and size ~ 80 micron was obtained in a similar manner omitting PLGA. XRD and DSC study confirmed decreased crystallinity in the presence of PLGA. No interaction between PLGA and DPZ was evident in the FTIR study. The microparticulate dispersions exhibited good in vitro injectability when tested using the texture analyzer (force < 5 N). When evaluated using the dialysis bag method (Himedia 12-14 kDa molecular weight cutoff), both microparticulate formulations exhibited controlled release up to 1 week in vitro. Further, low burst release of ~ 10% at the end of 6 h in the ex vivo chicken muscle study proposes great promise. Our data propose the facile extemporaneous generation of microparticles as a practical and promising approach for development of long-acting injectables. This facile approach could serve as platform technology for other drug candidates., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Purpose: People 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., Methods: Four 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., Results: The 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., Conclusions: Current results indicate that many PLHIV would prefer LAI ART. The reported utilities may be useful in economic modeling comparing oral vs. LAI ART., (© 2022. The Author(s).)

Aim Results from clinical trials support the use of oral antipsychotics for treatment of early or first-episode psychosis in patients with schizophrenia. This paper will review literature on the advantages of early initiation of treatment for schizophrenia and the clinical benefits of early use of long-acting injectable antipsychotics ( LAIs). Method A comprehensive literature review was conducted to identify published literature on the use of LAIs early in the treatment of schizophrenia. Results Although there is a higher response rate to initial antipsychotic treatment for a first-episode of schizophrenia than with subsequent antipsychotic treatment, we have not effectively addressed this issue. Poor adherence to treatment is a primary cause of relapse and rehospitalization in subsequent years and was associated with higher relapse rates resulting in devastating effects and substantial economic burden. The costs of nonadherence were estimated to be $1.48 billion. Thus, a major challenge with the treatment of schizophrenia is changing poor adherence to persistence with antipsychotic therapy. LAIs are known to be at least as effective as oral antipsychotics for treating schizophrenia, and yet are underutilized. Further, LAIs address many of the problems associated with adherence to oral therapy. Recent evidence suggests that LAIs are effective for treating first-episode psychosis and for early initiation of treatment for schizophrenia. Conclusion Although consistent antipsychotic treatment represents a critical part of treatment, a person-centred approach to treating schizophrenia is essential for all aspects of care, including establishing and maintaining a therapeutic alliance, strengthening shared decision-making and adherence, and achieving long-lasting recovery. [ABSTRACT FROM AUTHOR]

Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18-70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (=3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150 mg eq. deltoid], day 8 [100 mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150 mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525 mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150 mg eq. deltoid/ gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n = 504; PP1M: n = 512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n = 37, 8%; PP1M: n = 45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. [ABSTRACT FROM AUTHOR]

This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, aged 18-65 years) were enrolled in 1 of 4 separately conducted panels (A to D). Each panel had 2 single-dose treatment periods (period 1, 1 mg intramuscular paliperidone immediate release [IR]; period 2, intramuscular PP3M 75−525 mg eq) separated by a washout of 7-21 days. Overall, 245 of 308 (79.5%) PP3M-dosed patients completed the study. Because the PK studies of panels A and C were compromised by incomplete injection in some patients, PK data from only panels B and D are presented. Safety data from all panels are presented. Peak paliperidone plasma concentration was achieved between 23 and 34 days, and apparent half-life was ∼2-4 months. Mean plasma AUC∞ and Cmax of paliperidone appeared to be dose-proportional. Relative bioavailability in comparison with paliperidone was ∼100% independent of the dose and injection site. Headache and nasopharyngitis were the most common (>7%) treatment-emergent adverse events. Overall, safety and tolerability were similar to those of the 1-month formulation. Results support a once-every-3-months dosing interval in patients with schizophrenia or schizoaffective disorder. [ABSTRACT FROM AUTHOR]

Long-acting injectable (LAI) drug suspensions consist of drug nano-/microcrystals suspended in an aqueous vehicle and enable prolonged therapeutic drug exposure up to several months. The examination of injection site reactions (ISRs) to the intramuscular (IM) injection of LAI suspensions is relevant not only from a safety perspective but also for the understanding of the pharmacokinetics. The aim of this study was to perform a multilevel temporal characterization of the local and lymphatic histopathological/immunological alterations triggered by the IM injection of an LAI paliperidone palmitate suspension and an analog polystyrene suspension in rats and identify critical time points and parameters with regard to the host response. The ISRs showed a moderate to marked chronic granulomatous inflammation, which was mediated by multiple cyto-/chemokines, including interleukin-1β, monocyte Chemoattractant Protein-1, and vascular endothelial growth factor. Lymphatic uptake and lymph node retention of nano-/microparticles were observed, but the contribution to the drug absorption was negligible. A simple image analysis procedure and empirical model were proposed for the accurate evaluation of the depot geometry, cell infiltration, and vascularization. This study was designed as a reference for the evaluation and comparison of future LAIs and to support the mechanistic modeling of the formulation–physiology interplay regulating the drug absorption from LAIs. [ABSTRACT FROM AUTHOR]

1.  Cabotegravir [(3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide] is an HIV-1 integrase inhibitor under development as a tablet for both oral lead-in therapy and long-acting (LA) injectable for intramuscular dosing. 2. Metabolism, pharmacokinetics and excretion were investigated in healthy human subjects who received either a single oral dose (28.2 mg) of [14C]cabotegravir in a mass balance study, or LA formulations of unlabeled cabotegravir (200–800 mg), intramuscularly or subcutaneously, in a separate study. Metabolism, distribution and excretion of [14C]cabotegravir were also investigated in mice, rats and monkeys. 3. Recovery of radioactivity in humans represented a mean total of 85.3% of the dose, including 26.8% in the urine. The mean apparent terminal phase half-life was similar for both cabotegravir and radioactivity, 39 h compared to 41 h. 4. Following oral, intramuscular and subcutaneous administration, cabotegravir was the major component in plasma and the glucuronic acid conjugate (M1) represented the predominant component in urine. Cabotegravir was present in bile along with its major metabolite (M1). 5. The primary metabolite of [14C]cabotegravir in mouse, rat and monkey was the same as that in human.In vitrophenotyping experiments demonstrated that cabotegravir was metabolized by UDP-glucuronosyltransferase (UGT) 1A1 and UGT1A9. [ABSTRACT FROM AUTHOR]

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole. [ABSTRACT FROM PUBLISHER]

Introduction: Safely tapering current antipsychotic medication, while balancing efficacy and tolerability, is an important consideration when switching patients from their antipsychotic therapy to a new treatment. The efficacy and tolerability of paliperidone palmitate one-month (PP1M) in Chinese patients switched from previous antipsychotic treatments were examined in order to develop effective switching and dosing strategies. Methods: A 13-week open-label, single arm, prospective, interventional study was conducted in Chinese patients (n = 610) with acute schizophrenia to examine their response, by previous treatment group, when switched to PP1M (75- 150 mg eq). Results: Among 610 patients with ≥ 30 % reduction in PANSS total score were 191/263 (72.6 %) risperidone/paliperidone extendedrelease patients, 36/52 (69.2 %) olanzapine patients, and 214/293 (73.0 %) other antipsychotic patients. Patient functioning and adherence were significantly (p ≤ 0.05) improved for all subgroups. Discussion: Patients on higher doses of prior antipsychotics generally took longer to withdraw from their current medication. Most patients were administered the 100 mg eq dose, and all subgroups received a similar mean dose (114-119 mg eq) of PP1M. Recommendations for transitioning patients to PP1M from each subgroup are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

Objective: To analyze the effect of Risperidone ISM on social functioning and health-related quality of life (HR-QoL) in both short- and long-term treatment of patients with schizophrenia., Patients and Methods: This analysis was based on data from both phases of the PRISMA-3 study, including 433 relapsed patients from the double-blind (DB) phase of the PRISMA-3 trial who were treated for 12-weeks with once-monthly (every 28 days) intramuscular Risperidone ISM 75 mg or 100 mg (n = 288), or placebo (n = 145), as well as 174 patients transitioning from the DB to an open-label 52-week extension (OLE) phase, plus 41 de novo patients treated on a stable maintenance dose of oral risperidone. The clinician-administered Personal and Social Performance (PSP) scale and the patient-reported 20-item Subjective Well-being under Neuroleptics scale (SWN-20) were used to measure social functioning and HR-QoL outcomes, respectively., Results: Risperidone ISM significantly improved PSP total score from baseline to endpoint (Day 85) versus placebo in the DB phase with mean change total score (95% CI) of 10.7 (9; 12) compared to 4.8 (3; 7) for placebo (p < 0.0001). The statistically significant improvement was present from the first measurement time point (Day 29). SWN-20-measured HR-QoL increased on average in patients treated with Risperidone ISM in the DB phase. A significant improvement was also observed for PSP and SWN-20 scores from the OLE baseline to week 52 for patients transitioning from the DB phase. Stable de novo patients maintained similar PSP and SWN-20 scores during the whole OLE phase., Conclusion: Risperidone ISM provided a rapid and sustained improvement in personal and social functioning, and HR-QOL without need of oral risperidone supplementation or loading doses. These findings, along with a fast onset of efficacy, could contribute to reinforcing the therapeutic alliance and possibly an earlier discharge. Moreover, patient functioning continued improving or was maintained with long-term treatment., Competing Interests: Robert Litman, is a Member, Speakers Bureau, for JNJ and for Allergan, Member, Scientific Advisory Board, Terran BioSciences. He participated as Investigator Coordinator in The United States of America and as Principal Investigator in the study PRISMA-3. Dieter Naber, has received consulting fees from Laboratorios Farmacéuticos Rovi, S.A. He served on the Data Monitoring Committee for Rovi at the present study. Lourdes Anta and Javier Martínez are employees of Laboratorios Farmacéuticos Rovi, S.A., the sole developer of Risperidone ISM. Yuriy Filts has participated as Investigator Coordinator in Ukraine and Principal Investigator in the study PRISMA-3. He also received fees from ROVI for his advice in some previous tasks related to PRISMA-3 study. Dr Yuriy Filts also reports personal fees from Suvion, Otsuka, Arkermes, ROVI, Intracellular Therapies, Janssen, Minerva Neurosciences, Gedeon Richter as principal investigator in clinical study, outside the submitted work. He also received fees for lecturing from Laboratorios Farmacéuticos Rovi, S.A., and Lundbeck. Christoph U. Correll, has been a consultant and/or advisor to or have received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. The authors report no other conflicts of interest in this work., (© 2023 Litman et al.)

Definition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient's characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM ® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM ® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia., (© 2023. The Author(s).)

Aim: To evaluate the impact of timing of aripiprazole once-monthly (AOM) initiation on healthcare resource utilization (HCRU), risk of hospitalization, and healthcare costs in patients with schizophrenia., Methods: A retrospective cohort study was conducted using data from the Merative MarketScan database (01/01/2013-12/31/2019). Adults aged ≥18 years with a new episode of care for schizophrenia and an AOM claim were included. Patients were classified into two cohorts based on the time between the first schizophrenia diagnosis and the first AOM claim (early cohort: ≤1 year; late cohort: >1 year). All-cause and psychiatric-specific HCRU, risk of hospitalization, and healthcare costs were evaluated over 1-year post-AOM initiation. The relationship between the timing of AOM initiation and HCRU was evaluated using negative binomial regression, and healthcare costs using generalized linear models (log-link with gamma distribution). Logistic regression was used to estimate the likelihood of hospitalization during the follow up period for both all-cause and psychiatric-specific hospitalization., Results: A total of 945 patients were included (early cohort: n  = 525; late cohort: n  = 420). At baseline, the early cohort had lower mean age, a greater proportion of males, and a lower mean Charlson Comorbidity Index score than the late cohort (all p  < .05). After adjusting for baseline demographic and clinical characteristics, all-cause and psychiatric-specific hospitalization during the 1-year follow-up period were statistically significantly higher for the late cohort versus the early cohort (all-cause: incident rate ratio [IRR] = 1.63, 95% confidence interval [CI]: 1.28-2.07, p  < .01; psychiatric-specific: IRR = 1.93, 95% CI: 1.46-2.55, p  < .01). The early cohort had statistically significantly lower adjusted all-cause ($21,686 versus $29,033; p  = .0002) and psychiatric-specific ($24,414 versus $32,461; p  = .0002) healthcare costs versus the late cohort., Limitations: This study utilized claims data, which are intended for administrative purposes rather than for research., Conclusions: This analysis extends previous evidence for the benefits of AOM in patients with new episodes of schizophrenia, by demonstrating lower HCRU, risk of hospitalization, and healthcare costs with early AOM initiation compared with later initiation.

Drug nano-/microcrystals are being used for sustained parenteral drug release, but safety and efficacy concerns persist as the knowledge of the in vivo fate of long-living particulates is limited. There is a need for techniques enabling the visualization of drug nano-/microcrystals in biological matrices. The aim of this work was to explore the potential of coherent anti-Stokes Raman scattering (CARS) microscopy, supported by other non-linear optical methods, as an emerging tool for the investigation of cellular and tissue interactions of unlabeled and non-fluorescent nano-/microcrystals. Raman and CARS spectra of the prodrug paliperidone palmitate (PP), paliperidone (PAL) and several suspension stabilizers were recorded. PP nano-/microcrystals were incubated with RAW 264.7 macrophages in vitro and their cellular disposition was investigated using a fully-integrated multimodal non-linear optical imaging platform. Suitable anti-Stokes shifts (CH stretching) were identified for selective CARS imaging. CARS microscopy was successfully applied for the selective three-dimensional, non-perturbative and real-time imaging of unlabeled PP nano-/microcrystals having dimensions larger than the optical lateral resolution of approximately 400 nm, in relation to the cellular framework in cell cultures and ex vivo in histological sections. In conclusion, CARS microscopy enables the non-invasive and label-free imaging of (sub)micron-sized (pro-)drug crystals in complex biological matrices and could provide vital information on poorly understood nano-/microcrystal–cell interactions in future. [ABSTRACT FROM AUTHOR]

Objective: To directly compare aripiprazole once-monthly 400mg (AOM 400) and paliperidone palmitate once-monthly (PP) on the Heinrichs-Carpenter Quality-of-Life Scale (QLS), a validated health-related quality of life and functioning measure in schizophrenia.Method: This 28-week, randomized, non-inferiority, open-label, rater-blinded, head-to-head study (QUALIFY) of AOM 400 and PP in adult patients (18-60 years) comprised oral conversion, initiation of AOM 400 or PP treatment, and continuation with intramuscular injections every 4weeks. The primary endpoint assessed non-inferiority and superiority on QLS total score analyzed using a mixed model for repeated measurements.Results: Of 295 randomized patients, 100/148 (67.6%) of AOM 400 and 83/147 (56.5%) of PP patients completed 28weeks of treatment. A statistically significant least squares mean difference in change from baseline to week 28 on QLS total score (4.67 [95%CI: 0.32;9.02], p=0.036) confirmed non-inferiority and established superiority of AOM 400 vs PP. There were also significant improvements in Clinical Global Impression - Severity scale and the Investigator's Assessment Questionnaire for AOM 400 vs PP, and pre-defined sub-group analyses revealed a consistent pattern of significance favoring AOM 400 in patients ≤35years. Common treatment-emergent adverse events in the treatment continuation phase were more frequent with PP vs AOM 400, and adverse events were the most frequent reason for discontinuation (27/137 [19.7%] for PP and 16/144 [11.1%] for AOM 400). All-cause discontinuation was numerically lower with AOM 400.Conclusion: Superior improvements on clinician-rated health-related quality of life and a favorable tolerability profile suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate. ClinicalTrials.gov identifier:NCT01795547. [ABSTRACT FROM AUTHOR]

Antiretroviral preexposure prophylaxis has huge potential for reducing the rates of new HIV infections in at risk populations. Oral and vaginal antiretroviral formulations have been evaluated in multiple Phase IIB and Phase III effectiveness trials and there is clear evidence that these products work when used. The converse is also true; antiretrovirals do not work when they are not used and unfortunately adherence is a problem for both HIV treatment and prevention. As a consequence, long-acting injectable and implantable antiretroviral formulations are being developed for the treatment and prevention of HIV infection. It is hoped they will reduce the burden of product adherence associated with the use of oral and topical products and improve clinical outcomes associated with their use. The purpose of this review is to summarize recent preclinical and clinical research in this area of HIV prevention. [ABSTRACT FROM AUTHOR]