Criminal behaviors and substance use disorder in psychiatric patients.

OBJECTIVE: People with mental illness are overrepresented throughout the criminal justice system. In Italy, the Judicial Psychiatric Hospitals are now on the edge of their closure in favor of small-scale therapeutic facilities (REMS). Therefore, when patients end their duty for criminal behaviors, their clinical management moves back to the outpatient psychiatric centers. Elevated risks of rule-violating behavior are not equally shared across the spectrum of psychiatric disorders. To broaden the research in this area, we analyzed sociodemographic, clinical, and forensic variables of a group of psychiatric patients with a history of criminal behaviors, attending an outpatient psychiatric service in Milan, focusing on substance use disorder (SUD). METHODS: This is a cross-sectional single center study, conducted from 2020. Seventy-six subjects with a history of criminal behaviors aged 18 years or older and attending an outpatient psychiatric service were included. Demographic and clinical variables collected during clinical interviews with patients were retrospectively retrieved from patients' medical records. Appropriate statistical analyses for categorical and continuous variables were conducted. RESULTS: Data were available for 76 patients, 51.3% of them had lifetime SUD. Lifetime SUD was significantly more common in patients with long-acting injectable antipsychotics therapy, a history of more than 3 psychiatric hospitalizations, and a history of previous crimes, particularly economic crimes. Additionally, this last potential correlation was confirmed by logistic regression. CONCLUSIONS: Data emerging from this survey provide new information about offenders with lifetime SUD attending an Italian mental health service. Our preliminary results should be confirmed in larger sample sizes.

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

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

Long Acting Ionically Paired Pamoate-based Suspension of Lurasidone: An exploration of Size Effects on in vitro Dissolution and in vivo Pharmacokinetic Behaviors.

Latuda® is an oral tablet approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. However, the clinical efficacy of Latuda® is compromised by patient noncompliance due to frequent daily administration, especially for patients experiencing severe schizophrenia, whose medication is often needed for several months to years. Hence, developing a long-acting injectable formulation of lurasidone is urgently needed. Herein, a poorly water-soluble lurasidone pamoate (LP) salt was synthesized via the facile ion pair-based salt formation technology. The solubility of LP was decreased by 233 folds compared with that of lurasidone hydrochloride (LH). Furthermore, suspensions of LH and LP with three different particle sizes, including 400 nm small-sized nanocrystals (SNCs), 4 µm medium-sized microcrystals (MMCs), and 15 µm large-sized microcrystals (LMCs) were prepared and characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The in vitro release results showed that particle sizes had great effects on the sustained release of LH, where large-sized particles exhibited superior sustained release than the smaller ones. Besides, LP suspensions exhibited better sustained release than LH suspensions at the same size scale. Moreover, the pharmacokinetics showed that LP LMCs produced an extended in vivo intramuscularly injectable profile for up to 45 days, which was 10 days longer than that of the LH LMCs. Our findings demonstrated that particle size had appreciable impacts on drug sustained release and provided valuable knowledge for the rational design of optimized micronized suspensions for long-acting injectables.

Long-acting injectable paliperidone palmitate induced severe cutaneous allergic reaction in a patient with first episode delusional disorder tolerating oral paliperidone regimen: a case report.

BACKGROUND: Paliperidone is a second-generation antipsychotic agent that is effective in the treatment of schizophrenia and schizoaffective disorder as well as an adjunct to mood stabilizers and antidepressants for bipolar and depressive disorders. Paliperidone is available in both oral and injection forms. Here we report an unexpected case of cutaneous allergic reaction induced by paliperidone long-acting injection (LAI) following oral tolerance. CASE PRESENTATION: A 55-year-old man with first episode delusional disorder was treated with paliperidone tablets with tolerance. On day seven he received the paliperidone LAI and developed an allergic reaction in minutes including flushing of the face, widespread urticaria with mild airway constriction. The allergic symptoms were relived following the administration of antihistamine within several minutes. CONCLUSION: The allergic reaction that occurred post administration of the paliperidone LAI but not the oral tablets suggest it is likely due to the excipients in the formulation of the LAI rather than paliperidone itself. This case highlights the necessity of monitoring allergic reactions in psychiatric patients when converting from oral to LAI format of paliperidone.

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia. METHODS: This retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods. RESULTS: Among 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p < 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 [SD $68,887] versus $74,131 [SD $75,941]), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 [SD $63,428] versus $68,403 [SD $72,088]) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status. CONCLUSIONS: SGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.

Effect of long acting injectable antipsychotics on course and hospitalizations in bipolar disorder - a naturalistic mirror image study.

PURPOSE: To determining whether the addition of a long-acting injectable antipsychotic (LAI-AP) has a positive effect on prognosis in bipolar disorder. MATERIALS AND METHODS: Medical records of patients with bipolar disorder who were using LAI-AP at least for one year in the community mental health center (CMHC) until March 2020 were investigated. Comparisons were made between the period of one year before and after the initiation of LAI-AP. Hospital admission was the primary outcome. Residual symptom severity and functionality were evaluated with Personal and Social Performance Scale (PSP), Young Mania Rating Scale (YMRS), and Beck Depression Inventory (BDI). RESULTS: There were 197 patients with bipolar disorder who were attending to the CMHC and 17 of them were under maintenance treatment with LAI-AP for at least one year. The LAI-APs used were aripiprazole (n = 8), paliperidone (n = 5) and risperidone (n = 4). Duration of illness was 13.5 ± 8.02 years and duration of LAI-AP treatment was 24.8 ± 22.74 months (median: 18). During the one-year period after the LAI-AP initiation, there were fewer days spent in hospital (2.5 ± 5.68 vs. 15.5 ± 20.59 days, p = .026) and the number of hospitalizations was lower than the year before the LAI-AP use (0.1 ± 0.39 vs. 0.9 ± 1.24 hospitalizations, p = .013). During the recovery period with LAI antipsychotics, there were mild residual symptoms presented with mean PSP (70.2), YMRS (1.7) and BDI (7.6) scores. CONCLUSION: LAI-AP use may have positive effect on course for selected patients with a long history of bipolar disorder.

Reducing long acting antipsychotic injection dosage frequency: A pilot study in a community mental health team.

BACKGROUND: Antipsychotic long acting injections (LAI) allow a range of dosage intervals to be administered. Short intervals can be inconvenient for patients and staff. There are few clinical reasons for using them yet this is common practice. AIMS: This study aimed to examine the feasibility of reducing LAI frequency with service user consent. METHODS: The study took place in a community mental health team in the north of England. A specialist mental health pharmacist reviewed records of all service users on LAI and drew up an action plan. Each service user then met with the consultant psychiatrist for medication review. RESULT: Nineteen out of thirty service users on LAI had intervals less than the maximum licensed. The frequency was reduced in eight cases. After 6 months follow-up, there was no deterioration in symptoms. In nine cases, antipsychotic doses were also reduced as a result of the review. CONCLUSION: Where a service user is prescribed a LAI with a short dosage interval consideration should be given to increase the interval. This can free up service user and staff time. A medication focused review can also lead to other benefits such as dosage reduction.

Impact of age and CYP2D6 genetics on exposure of aripiprazole and dehydroaripiprazole in patients using long-acting injectable versus oral formulation: relevance of poor and intermediate metabolizer status.

PURPOSE: Tailoring medication dosing for the individual patient is complex, and many factors can influence drug exposure. We investigated the effect of age and CYP2D6 genotype on aripiprazole and dehydroaripiprazole exposure in patients using long-acting injectable (LAI) or oral aripiprazole. METHODS: Matched data on serum concentration of aripiprazole and CYP2D6 genotype of patients using oral or LAI aripiprazole were included retrospectively from a therapeutic drug monitoring service. The patients were divided into the following CYP2D6 genotype-defined categories: poor metabolizers (PMs), intermediate metabolizers (IMs), normal metabolizers (NMs), and ultrarapid metabolizers (UMs). Linear mixed model analyses were used to evaluate the impact of CYP2D6 genotype on dose-adjusted serum concentrations of the active moiety of aripiprazole+dehydroaripiprazole in relation to age and formulation. RESULTS: We identified 635 patients (mean age = 40.1 years, 9.4% ≥ 65 years, 53.7% females) using LAI (n = 166) or oral formulation (n = 469). The genotype-predicted CYP2D6 phenotype subgroups were 2.4% UMs, 82.0% NMs, 8.0% IMs, and 7.2% PMs. Age did not significantly affect exposure of the active moiety of aripiprazole+dehydroaripiprazole in the LAI (p = 0.071) or oral (p = 0.14) subgroups. Compared with CYP2D6 NMs, PMs and IMs had significantly increased exposure of the active moiety of aripiprazole+dehydroaripiprazole in the LAI (1.7-fold higher, p < 0.001, and 1.5-fold higher, p < 0.001) and oral (1.7-fold higher, p < 0.001, and 1.6-fold higher, p < 0.001) subgroups. CONCLUSIONS: In conclusion, doses should be adjusted according to CYP2D6 genotype when initiating treatment with aripiprazole LAI or tablets, while advanced age do not affect the exposure of the active moiety of aripiprazole treatment regardless of formulation.

Real-world effectiveness of long-acting injections for reducing recurrent hospitalizations in patients with schizophrenia.

BACKGROUND: The comparative effectiveness of antipsychotic long-acting injections (LAIs) and oral medication is not clear due to various methodological problems. METHODS: To compare the effectiveness of LAIs and oral antipsychotics in preventing readmission in patients with schizophrenia, we performed a within-subject analysis of data collected from 75,274 patients hospitalized with schizophrenia over a 10-year period (2008-2017). Readmission rates were compared according to medication status (non-medication, oral medication alone, and LAI medication). Each admission episodes were compared according to medication status before admission. RESULTS: Total 132,028 episodes of admission were analyzed. During 255,664 person-years of total observation, 101,589 outcome events occurred. Comparing LAI to only oral medication, IRR was 0.71 (0.64-0.78, P < 0.001). IRR of LAI to only oral medication of first index admission was 0.74 (0.65-0.86). As hospitalization was repeated, IRR of second, third, and fourth or more index admission decreased 0.65 (0.53-0.79), 0.56 (0.43-0.76), and 0.42 (0.31-0.56), respectively. CONCLUSIONS: LAI treatment reduced the readmission rate by 29% compared with oral medication in real-world settings. Moreover, LAIs reduced the readmission rate by 58% in patients with repeated admissions. The more readmissions, the greater the effect of LAIs in reducing the risk of re-hospitalization compared with oral antipsychotics.

Nursing Advocacy and Long Acting Injectables to Reduce High Readmission Rates: Quality Initiative.

INTRODUCTION: Nonadherence to medications for schizophrenia relates to frequent readmissions. Long-acting injectable (LAI) medications are shown to increase adherence and reduce admissions. AIMS: (1) Identify frequent readmissions to psychiatry. (2) Improve nursing advocacy for patients appropriate for LAIs through in-service. METHODS: Chart audits were employed for data collection. Academic detailing and dashboards were used for voluntary nursing education. The chart audit spanned 90 days pre and post in-service. All admissions to psychiatry were screened; patients with readmissions under 30 days (with the same admitting diagnosis), a schizophrenia spectrum diagnosis, and nonadherent with oral antipsychotics were included. Results: Forty-four patients met criteria and amassed 49 frequent readmissions. For inclusion criteria, the admission rate decreased by 53% and LAI prescriptions increased by 9%. Three patients from the first audit group and one from the second were initiated on LAIs. CONCLUSIONS: Attitudes toward LAIs may be improving based on RN advocacy and collaboration.

Factors That Affect Continuation of Antipsychotic Long-Acting Injections.

Long-acting injection (LAI) is a drug administration method that reduces symptoms and prevents recurrence or relapse of schizophrenia. We examined factors related to the continuation of LAI treatment. The study population included patients with schizophrenia who were undergoing LAI treatment involving risperidone, paliperidone, or aripiprazole at Fujita Health University Hospital between October 2009 and June 2017. We assessed the continuation rate of LAI treatment at six months, and collected patient characteristics such as medication history. Furthermore, we classified patients into two clusters according to the reason for introducing LAI based on a previous study (Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, Heres et al.). The study included 82 patients (mean age, 44.9 ± 15.0 years); the continuation rate of LAI after six months was 63.4%. Factors that affected LAI continuation included cluster II [adjusted odds ratio (OR): 5.74, p = 0.017], switching from the same component as LAI (adjusted OR: 7.13, p < 0.001), and diazepam conversion rate (adjusted OR: 0.88, p < 0.001). LAI significantly improved the continuation rate of treatment in the patient group belonging to cluster II. Furthermore, based on other factors and reasons for discontinuation, LAI should be preferably commenced in patients with a more stable condition.

The effects of different periods of co-administration of oral and long-acting injectable aripiprazole: A propensity score analysis.

OBJECTIVE: Long-acting injectable (LAI) aripiprazole is recommended to be combined with oral aripiprazole for 2 weeks after its introduction. However, we often experience patients who require more than 2 weeks of combined use. Therefore, differences in combination periods need to be examined. METHODS: This was a case-control study. We surveyed prescription profiles for oral aripiprazole administration in conjunction with LAI aripiprazole introduction and assessed the clinical course during a 12-week follow-up period. RESULTS: Among 121 patients, 58 (47.9%) were administered both oral and LAI aripiprazole for more than 2 weeks. Although there was no significant difference in treatment failure (defined as psychiatric hospitalization or discontinuation of LAI aripiprazole from any cause) between the two groups, the group that was administered oral aripiprazole for more than 2 weeks received less additional benzodiazepines compared with that of the 2 weeks group (adjusted odds ratio, 0.055; 95% confidence interval [0.0060, 0.50]; p < 0.01). CONCLUSIONS: Our data support a flexible co-administration period for oral and LAI aripiprazole in consideration of the pharmacokinetics, but further studies are needed.

[Long-acting antipsychotics: The QAAPAPLE algorithm review]. / Antipsychotiques à Action Prolongée: Révision de l'algorithme QAAPAPLE.

BACKGROUND: Eight years ago, a committee of experts from 4 Quebec university psychiatry departments has provided the QAAPAPLE algorithm in order to guide clinicians in their use of long-acting antipsychotics (LAAP) for patients with psychotic disorders. OBJECTIVE: Update the QAAPAPLE algorithm. METHODS: Using a qualitative and selective literature review, the experts have focused on several aspects related to the use of LAAP and the relevance of modifying the algorithm: 1) new data on LAAP (including polypharmacy and co-prescription with clozapine, dose frequency/interval); 2) perception and attitude regarding algorithms and evidence; 3) difficulties in implementing algorithms; 4) polypharmacy involving LAAP and co-prescriptions with clozapine; 5) partner patients perspective on the algorithm. RESULTS: Thirteen meta-analysis were published and completed observational studies (including those on national registries), confirming the LAAP benefits. Literature adds specifications about using some drug associations as well as dose frequency and interval. Therefore, scientific advances have been considered to modify the algorithm. CONCLUSION: Interacting with Quebec psychiatrists, we have examined changes in prescription and literature to better understand the use of algorithm. The committee has updated the QAAPAPLE algorithm to guide clinicians in using LAAP along the path of patients with psychosis as early as the first episode and through different clinical settings (including treatment resistance) in order to have a more flexible and user-friendly treatment.

CONTEXTE: Il y a 8 ans, un comité d'experts issus des 4 départements de psychiatrie universitaires québécois a proposé l'algorithme QAAPAPLE visant à guider les cliniciens à l'égard de l'utilisation des APAP pour les patients atteints de troubles psychotiques. OBJECTIF: Faire une mise à jour de l'algorithme QAAPAPLE. MÉTHODES: Grâce à une revue qualitative et sélective de la littérature, les experts se sont intéressés à plusieurs aspects en lien avec l'utilisation des APAP et sur la pertinence de modifier l'algorithme: 1) données nouvelles sur les APAP (incluant polypharmacie et co-prescription avec clozapine, fréquence et intervalle d'administration); 2) perception et attitude sur des algorithmes et données probantes; 3) difficultés d'application des algorithmes; 4) polypharmacie impliquant les APAP et co-prescriptions avec clozapine; 5) avis des patients partenaires sur l'algorithme. RÉSULTATS: 13 méta-analyses ont été publiées et complètent les études observationnelles (incluant celles sur des registres nationaux) confirmant les avantages des APAP. La littérature apporte des précisions quant à l'utilisation de certaines associations médicamenteuses, fréquence et intervalle d'administration. L'algorithme a donc été modifié en tenant compte des avancées scientifiques. CONCLUSION: En interaction avec les psychiatres québécois, nous avons examiné les changements des prescriptions, la littérature, pour mieux comprendre l'utilisation de l'algorithme. Le comité a actualisé l'algorithme QAAPAPLE, pour mieux guider les cliniciens dans l'utilisation des APAP dans la trajectoire des patients atteints de psychoses dès le premier épisode et à travers les différents contextes cliniques (incluant la résistance au traitement) afin de le rendre plus flexible et convivial. IMPLICATIONS CLINIQUES: Les études observationnelles (naturalistes) montrent que les APAP réduisent les rechutes, les ré-hospitalisations et la surmortalité. La palette de fréquence d'injection permet des intervalles de deux semaines à trois mois, ce qui permet un ajustement aux besoins du patient en termes de stabilité clinique et de fréquence des contacts. Les APAP restent une modalité thérapeutique sous-utilisée, un algorithme peut aider à se repérer et donc en faciliter l'utilisation. LIMITES: Le comité a produit une revue de la littérature narrative et systématique, plutôt que quantitative; toutefois, il s'est complètement basé sur les conclusions des méta-analyses. La participation aux sondages reliés à ce projet demeure sous optimale. Le comité n'a pas examiné la littérature concernant les aspects spécifiques reliés à la prescription d'APAP chez les personnes âgées ou les enfants.

Discontinuation rates during long-term, second-generation antipsychotic long-acting injection treatment: A systematic review.

AIM: The aim of this review was to analyze the discontinuation rates during long-term treatment with second-generation antipsychotic long-acting injection (SGA-LAI) in adults with either schizophrenia spectrum or bipolar disorders. METHODS: A systematic search (PubMed, Scopus, and the Cochrane Library) of studies published in English (1 January 2001-12 October 2018) identified 1214 abstracts, which were analyzed independently by the author and two colleagues. Studies were retrieved and reviewed if they reported primary data on the discontinuation rate before the study end during treatment lasting ≥36 weeks. Data were extracted from 51 articles meeting the inclusion criteria. RESULTS: In all head-to-head comparisons, and studies on patients with schizophrenia spectrum or bipolar disorders, the discontinuation rate before the study end in patients treated with SGA-LAI was, at best, similar to that recorded in patients treated with first-generation antipsychotics in either oral or LAI formulations or with oral SGA. In particular, in most of the SGA-LAI long-term studies, the rate of premature dropout was higher than 50%. CONCLUSION: Reviewed data suggest that SGA-LAI show no clear superiority over less expensive drugs (including first-generation antipsychotic LAI and oral antipsychotic formulations) in reducing the risk of premature antipsychotic discontinuation. Thus, alternative strategies should be considered to improve medication persistence and lower discontinuation rates in patients with severe psychiatric disorders. Planning tailored, individualized, and integrated approaches (including frequent clinical evaluations, and behavioral or other flexible techniques adaptable to different settings and patients) may be an effective intervention for improving patient adherence in long-term pharmacological treatment regimens.

Second-generation antipsychotic long-acting injections in bipolar disorder: Systematic review and meta-analysis.

BACKGROUND: Non-adherence is a significant problem in bipolar disorder. Second-generation antipsychotics (SGA) long-acting injections (LAIs) may improve adherence in bipolar disorder and may prevent relapses. However, the evidence is limited and conflicting. OBJECTIVE: The objective of this study was to evaluate efficacy and safety of SGA LAIs in bipolar disorder. METHOD: Systematic review and meta-analysis of randomised controlled trials (RCTs) (≥6 months duration) investigating safety and efficacy of SGA LAIs for bipolar disorder. We searched Pubmed, Embase, CINAHL, Cochrane, PsycINFO, LiLACS, www.clinicaltrials.gov up to October 2016. We also contacted the manufacturers of SGA LAIs. Primary efficacy and safety outcomes were relapse rate and all-cause discontinuation respectively. RESULTS: Total of seven RCTs (n = 1192) were included. SGA LAIs show superiority over placebo for study-defined relapse rate (RR = 0.58, 95% CI = 0.49-0.68, P < 0.00001) and all-cause discontinuation (RR = 0.72, 95% CI = 0.64-0.82, P < 0.00001). However, no significant difference was found between SGA LAIs and oral active control for relapse rate (RR = 0.92, P = 0.79) and all-cause discontinuation (RR = 1.2, P = 0.31). In terms of secondary outcomes, SGA LAIs performed better than placebo in relapse to mania/hypomania, young mania rating scales (YMRS), clinical global impression-severity (CGI-S), montgomery-asberg depression rating scale (MADRS). There was no significant difference between SGA LAIs and oral active control regarding relapse to mania/hypomania, YMRS, CGI-S, extra-pyramidal side effects (EPSEs), weight gain. However, the active control performed better than SGA LAIs in relapse to depression, MADRS, and prolactin-related AEs. CONCLUSIONS: Current evidence is very limited to support the use of SGA LAIs (compared to oral medication) in bipolar disorder. Further high-quality studies, particularly comparing SGA LAIs with active control, are warranted.

Injectable sustained release PLA microparticles prepared by solvent evaporation-media milling technology.

The objective of this study was to develop agomelatine (AGM) intramuscular sustained release PLA microparticles by using solvent evaporation combined with wet milling technology. The final preparation had a regular and homogeneous particle size of approximately 35 µm, as measured by laser diffraction particle size analysis and scanning electron microscopy (SEM). The drug was confirmed to be within the carrier in an amorphous state through differential scanning calorimetry (DSC) and power X-ray diffraction (PXRD) experiments. Additionally, Fourier transform infrared spectroscopy (FT-IR) analysis was applied to confirm that there was hydrogen bonding between the drug and polymer at the molecular level. In vitro release experiments indicated that the drug could achieve long-term sustained release over the period of one month, with only a 3.07% burst release, due to the involvement of the polymer and removal of drug adsorbed on the surface during the wet grinding process. The dominant release mechanism was considered to be diffusion of the drugs in the initial period. Following this, with the hydrolysis of PLA to form a colloidal viscous layer, drug release is due to the combined effect of diffusion and erosion of the polymer matrix. Additionally, drug release behavior is closely related to the degradation mechanism of the polymer carrier. The results suggest that AGM could be developed as a potential delivery system for long-acting intramuscular administration with extensive application prospects.

Risk of discontinuation of antipsychotic long-acting injections vs. oral antipsychotics in real-life prescribing practice: a community-based study.

OBJECTIVE: To compare the risk of discontinuation of ambulatory antipsychotic treatment in persons treated with antipsychotic long-acting injections (LAIs) or by oral antipsychotics (OAPs). METHODS: The study was performed in a representative sample of persons newly treated with OAPs (n = 6904) affiliated to the French Insurance Healthcare system. The risk of all-cause discontinuation was compared in patients prescribed OAPs (n = 246) vs. matched patients prescribed LAIs (n = 246) using multivariate survival analyses. Confounding by indication was minimized by matching on type of antipsychotic drug and by the high-dimensional propensity score method. RESULTS: Discontinuation was more frequent with OAPs (69%) compared to LAIs (57%) [adjusted relative risk (aRR) = 1.6, 95% CI 1.23-2.07]. Risk of discontinuation was higher for first-generation (FGA) OAPs vs. FGA LAIs (aRR = 1.94, 95% CI 1.22-3.08) as well as for second-generation (SGA) OAPs vs. SGA LAIs (aRR = 1.58, 95% CI 1.15-2.17). Over the 6-month period after discontinuation of LAIs, a new antipsychotic drug was dispensed in 58% of patients, the most frequent pattern being dispensing of the same LAI as that prescribed before discontinuation. CONCLUSIONS: Although less frequent than with OAPs, the rate of ambulatory treatment discontinuation was high with LAIs. Prescription of LAIs should be associated with intervention strategies aimed at promoting medication adherence.

Follow-up study of patients treated with olanzapine pamoate in France in real-life treatment situation.

OBJECTIVE: To characterize patients treated with olanzapine pamoate in French centers and investigate the conditions of use of olanzapine pamoate in real-life treatment situation. METHODS: Data came from French sites participating in an international post-authorization safety study. In this observational study, patients diagnosed with schizophrenia were receiving commercially available olanzapine pamoate, in accordance with their physician's usual standard of care. Data were collected during routine visits within the standard course of patient care. RESULTS: One hundred and thirty eight patients (male, 73.9%; mean age, 39.4 years; mean duration of disease, 12.7years) received olanzapine pamoate and were included in the study by 32 investigative psychiatrists distributed across 20 different sites (psychiatric hospitals). During the period of analysis, a total of 2975 injections of olanzapine pamoate was administered to the patients. The mean duration of olanzapine pamoate exposure was 475 days (1.3years). During follow-up, 13.8% of all patients had at least one psychiatric hospitalization, 15.9% had at least one same-day psychiatric hospitalization (information documented for 116patients), and 44.2% received at least one concomitant drug. Three cases of post-injection delirium/sedation syndrome were reported during the analysis period. Treatment emergent adverse events (incidence, 20.3%) were in line with the known profile of olanzapine. CONCLUSION: Patients were administered olanzapine pamoate and monitored in compliance with label recommendations. The safety profile assessment of olanzapine pamoate in actual conditions was consistent with that described in clinical studies.

Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial.

BACKGROUND: Recently, long-acting injection (LAI) of second-generation antipsychotics has become a valuable strategy for the treatment of schizophrenia. However, few studies have compared the effects of different LAI antipsychotics on cognitive functions so far. The present study aimed to compare the influence of risperidone LAIs (RLAI) and paliperidone palmitate LAIs (PP) on cognitive function in outpatients with schizophrenia. METHODS: In this 6-month, open-label, randomized, and controlled study, 30 patients with schizophrenia who were treated with RLAIs were randomly allocated to the RLAI-continued group or the PP group. At baseline and 6 months, the patients were evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) that was the primary outcome of the study. The Subjective Well-being under Neuroleptic drug treatment-Short form (SWNS), the Positive and Negative Syndrome Scale (PANSS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores were secondary outcome variables and they were tested at the same time points. RESULTS: The two groups did not differ in terms of PANSS, DIEPSS, or SWNS total score changes. However, the BACS score for the attention and processing speed item showed higher improvement in the PP group than the RLAI group (p = 0.039). CONCLUSIONS: The results of this preliminary study suggest that PPs may improve attention and processing speed more than RLAIs. Anyway, a replication in a larger and double-blind study is needed. TRIAL REGISTRATION: UMIN000014470 . Registered 10 July 2014.

Control of parasitic infection with ivermectin long-acting injection (IVOMEC® GOLD) and production benefit in first-season grazing cattle facing a high-level larval challenge in Germany.

Gastrointestinal and pulmonary nematode infections are affecting the health and productivity of grazing cattle worldwide. To evaluate the effects of a single treatment with ivermectin long-acting injection (IVM LAI; IVOMEC® GOLD, Merial; 3.15 % ivermectin w/v) in first-grazing season cattle, two studies were conducted under continued stocking conditions for 84 or 100 days in Bavaria, Germany. Each study involved 68 naturally infected, approximately 4- to 6-month-old Brown Swiss bull calves. Animals were blocked based on pretreatment body weights. Within each block of four animals, animals were randomly assigned to treatments: one to saline (control) and three to IVM LAI. Treatments were injected at 1 mL/50 kg body weight subcutaneously in front of the shoulder. Animals in both studies were managed as one herd each grazing together. Cattle were weighed and fecal samples were collected pretreatment and at intervals thereafter for determination of weight gain and treatment efficacy, respectively. Fecal examination including composite fecal culture indicated the presence of nematodes of the genera Cooperia (dominating), Haemonchus, Nematodirus, Ostertagia, Strongyloides, Trichostrongylus, Trichuris, and Dictyocaulus, and Moniezia cestodes in the cattle. Following treatment, IVM LAI-treated cattle did not shed any Dictyocaulus larvae for 84 days while controls continued to pass larvae. Compared to the controls, IVM LAI-treated cattle had significantly (p < 0.01) lower strongylid egg counts at each occasion. Percentage reductions were ≥94 % up to 70 days after treatment and were ≥83.9 and 58.9 % at 84 and 100 days. Over the 84- or 100-day study periods, IVM LAI-treated cattle gained significantly more weight than the controls: 22.7 and 12.4 kg, respectively. The two studies demonstrated a high efficacy of IVM LAI against gastrointestinal and pulmonary nematode infections under field conditions in Germany which was associated with significant benefit as to weight gain.