Long-acting Injectable Formulations Research Articles

Differences of use between paliperidone palmitate 3 month and paliperidone palmitate 1 month in real practice, with psychotic patients

IntroductionPaliperidone palmitate 1-month (PP1M) is a Long-acting injectable antipsychotic formulation, approved for the treatment of schizophrenia and schizoaffective disorder. Recently, paliperidone palmitate 3-months (PP3M) formulation was introduced, which maintains stability while offering a longer dosing interval for the maintenance treatment in patients previously treated with PP1M. Despite of this, many patients are treated with PP1M without transition to PP3M.ObjectivesTo identify variables explaining maintenance of PP1M treatment instead of going to PP3M. We hypothesize that more severe patients are delayed in transition to PP3M because of expectation to complete stabilization.MethodsA descriptive analysis of 123 patients, diagnosed with psychotic disorders, on treatment with paliperidone palmitate 1 month or 3 months, was performed. Age, sex, type of paliperidone treatment, hospitalizations after the initiaton of treatment, years since diagnosis, polytherapy and toxic habits were some of the variables measured and compared between both groups (PP1M and PP3M).ResultsMost of patients (63,41%) were on PP3M. Both groups shared characteristics like male sex predominance, schizophrenia as the most common diagnosis, having a recent onset diagnosis, same frequency of polypharmacy and same pattern of drug consumption. There was a slight difference between both groups regarding severity. PP1M and PP3M showed respectively 33% and 16,7% of admissions after initiation.ConclusionsNo clear pattern determines less transition to PP3M from PP1M. No statistical difference was found except form the difference found in admission after change of treatment (to PP1M or PP3M), which could reflect influence of severity in treatment. Future research is needed in order to better elucidate this association.DisclosureNo significant relationships.

Paliperidone palmitate-induced enuresis: a case report

IntroductionSchizophrenia is a severe mental illness that requires long-term treatment with antipsychotics and the intramuscular (IM) long-acting injectable (LAI) formulations may enhance treatment adherence. Some antipsychotics have been associated with enuresis, including atypical antipsychotics such as risperidone(6.2%), quetiapine(6.7%), olanzapine (9.6% ) and clozapine (20.7%) [1]. Although oral paliperidone has been related to urinary incontinence, there is only 1 report of urinary incontinence linked to monthly paliperidone palmitate [2]. [1] Harrison-Woolrych, M., Skegg, K., Ashton, J., Herbison, P., Skegg, D.C., 2011. Nocturnal enuresis in patients taking clozapine, risperidone, olanzapine and quetiapine: comparative cohort study. British Journal of Psychiatry 199, 140–144. doi:10.1192/bjp.bp.110.087478 [2] Karslıoǧlu, E.H., Özalp, E., Çayköylü, A., 2016. Paliperidone Palmitate-induced Urinary Incontinence: A Case Report. Clinical Psychopharmacology and Neuroscience 14, 96–100. doi:10.9758/cpn.2016.14.1.96ObjectivesTo establish an association between paliperidone palmitate and enuresis.MethodsCase report and a narrative review of the literature.ResultsThe patient was a 25-year-old healthy man when he was diagnosed with schizophrenia. Doctors prescribed paliperidone palmitate (LAI) 200mg monthly and he started to complain of enuresis. He was clearly suffering with this unpleasant and embarrassing adverse effect so the LAI was reduced to 150mg. Enuresis remained, so it was prescribed oxybutynin 20 mg/day and the patient improved.ConclusionsWe reported a case in which enuresis is likely to be associated with high-dose paliperidone LAI (with no clinical evidence of an organic cause). To treat it, the most effective strategy was oxybutynin 20 mg/day. This case is also important to show the impact of this symptom, which is not actively investigated.DisclosureNo significant relationships.

Efficacy and tolerability Aripiprazole once-monthly long-acting injectable in schizophrenia. Two-injection start regimen

IntroductionAripiprazole once-monthly is a long-acting intramuscular injectable formulation of aripiprazole. The starting dose can be administered by following one of two regimens: • One injection start: On the day of initiation, administer one injection of 400 mg Aripiprazole once monthly and continue treatment with 10 mg to 20 mg oral aripiprazole per day for 14 consecutive days • Two injection start (New regimen): On the day of initiation, administer two separate injections of 400 mg Aripiprazole once monthly at separate injection sites, along with one 20 mg dose of oral aripiprazole.ObjectivesTo assess the effectiveness and tolerability of Aripiprazole long-acting injectable (ALAI) in patients with schizophrenia. The starting dose was administered following the two injection start regimenMethodsSample:10 patients with schizophrenia (DSM 5 criteria) who started treatment with ALAI. The starting dose was administered following the two injection start regimen. On a tri-monthly basis, the following evaluations were performed during a follow-up period of 6 months: The Clinical Global Impression-Schizophrenia scale (CGI-SCH), treatment adherence, the number of hospitalizations and Side effects reportedResultsMean variations from baseline scores at 6 months was (-1.1 ±0.89) on the GCI-SCH. The percentage of patients who remained free of admissions at the end of the 6 months was 90%. The rate of adherence to treatment after 6 months was 80%. The most frequent side effect was transient mild insomnia (20%) .ConclusionsAripiprazole long-acting injectable (The starting dose was administered following the two injection start regimen) is effective, safe and well tolerated in clinical practice conditionsDisclosureNo significant relationships.

Neuroleptic Malignant Syndrome: A case report and a literature review

IntroductionNeuroleptic malignant syndrome (NMS) may be a life-threatening neurologic crisis primarily emerging as an idiosyncratic reaction to antipsychotic agent use, and characterized by a particular clinical syndrome of mental status alter, rigidity, fever and dysautonomia. Mortality results straightforwardly from the dysautonomic manifestations of the disease and from systemic complications.ObjectivesTo describe an unusual clinical case in order to determine the management regarding medication and electroconvulsive therapy (ECT), and provide an overview of NMS for the general practitioner with the most up-to-date information on etiology, workup, and management.MethodsWe report a case involving a 55-year-old man with paranoid schizophrenia disorder who presented with hyperthermia, hemodynamic instability, miosis, muscular rigidity, urinary incontinence, catatonic signs and mutism after combining several antipsychotics at the same time: long-acting injectable form of paliperidone, aripiprazol and haloperidol.ResultsGuidelines for specific medical treatments in NMS are based upon case reports and clinical experience. Generally used agents are dantrolene, bromocriptine, and amantadine. A conceivable approach is to start with benzodiazepines along with dantrolene in moderate or severe cases, followed by the addition of bromocriptine or amantadine. ECT is generally reserved for patients not responding to other treatments.ConclusionsNMS is an uncommon adverse drug reaction, with a multifactor pathophysiology and manifestation. Early diagnosis and interruption of antipsychotic therapy is the first-line treatment, followed by supportive care and pharmacotherapy. ECT is an effective treatment when supportive treatment together with pharmacotherapy fails. It could be considered first line in severe life-threatening situations. It is advisable to consider maintenance ECT due to the high risk of relapse.DisclosureNo significant relationships.

Evaluation of a long-acting injectable formulation of omeprazole in healthy dogs.

BackgroundTo evaluate the efficacy of a single intramuscular adminsitration of long‐acting omeprazole (LA‐OMEP) in increasing gastric pH in dogs.HypothesisWe hypothesized that LA‐OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration.AnimalsNine healthy research dogs.MethodsProspective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA‐OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined.ResultsThe mean onset of action for the LA‐OMEP was 98.11 min (SD 46.39). The mean number of days the dogs' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3‐7) and 5.25 days for MPT pH ≥4 (range, 3‐7). Long‐acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs.Conclusions and Clinical ImportanceThe LA‐OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed.

Combination therapy of modified electroconvulsive therapy and long-acting injectable aripiprazole for dopamine supersensitivity psychosis: a case report

ABSTRACT In the treatment of schizophrenia, long-term pharmacotherapy with D2-receptor antagonists can induce dopamine supersensitivity psychosis (DSP). We report a male patient with schizophrenia with suspected DSP due to excessive polypharmacy. He was hospitalized for several years. Most psychotropic drugs were reduced and subsequently stopped without the exacerbation of symptoms by administering modified electroconvulsive therapy (mECT). Aripiprazole was then selected as the main drug for treatment, which was subsequently changed to the long-acting injection formulation. He was eventually discharged and returned home. Combination therapy with mECT and aripiprazole, especially the long-acting injectable formulation, may help improve and prevent DSP.

Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review.

Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients. MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. 33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations. While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.

Modelling Shows the Negative Impact of Age Dependent Pharmacokinetics on the Efficacy of Oxytetracycline in Young Steers.

The effect of age dependent pharmacokinetics (PK) on the clinical efficacy of oxytetracycline (OTC) against Bovine Respiratory Disease (BRD) in beef cattle was studied, using a Physiologically Based Pharmacokinetic (PBPK) model. The model includes a bodyweight dependent renal clearance. To mimic/reproduce the long terminal half-live a bone forming tissue compartment was considered. Data for the development, calibration and validation of the model were obtained from public literature. To integrate the PK with the pharmacodynamics (PD) of OTC, Monte Carlo simulations were performed using this PBPK model to predict time-concentration curves for two commonly used dosing regimens of short-acting and long-acting injectable OTC formulations in virtual populations of 5,000 steer calves of 100 kg and 400 kg. These curves were then used to calculate the value of the PKPD index for OTC, which is the ratio of the area under the concentration-time curve for 24 h (AUC24h) over the minimum inhibitory concentration (MIC) of the target pathogen (AUC24h/MIC). The MIC values were for Mannheimia haemolytica, the dose-limiting pathogen for BRD. This integration of PBPK and PD for OTC used for the treatment of BRD in calves indicated that the Probability of Target Attainment (PTA) was sufficient for efficacy in calves of 400 kg, but insufficient for calves of 100 kg, when using a long acting dosing regimen of 20 mg/kg BW, twice, with a 48-h interval. The use of a dosing regimen of 10 mg/kg BW/day for 4 days predicted sufficient PTAs in both age groups.

Synthesis and structural characterization of two novel olanzapine cocrystals with decreased or enhanced dissolution rate

Olanzapine (OLZ) is a second-generation atypical anti-schizophrenia drug, and it had been developed into various formulations, including immediate release and long-acting formulations. Specific solubility properties of OLZ are very important to design formulations for specific administration. In present work, two novel cocrystals of OLZ were synthesized and characterized (OLZ-KAE·0.75EA·0.25H2O, OLZ-ORC, KAE = kaempferol, ORC = orcinol). Single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), synchronous thermal analysis and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) were used to characterize the structure of the cocrystals. Hirshfeld surface analysis was used to understand intermolecular interactions in cocrystals. In OLZ-KAE·0.75EA·0.25H2O cocrystal, the ethyl acetate (EA) and H2O exist as channel crystalline solvate, and they can easily escape from the lattice channel. Powder dissolution study showed that OLZ-ORC improved the dissolution rate of OLZ in PH 6.8 phosphate buffer. However, OLZ-KAE·0.75EA·0.25H2O and its desolvation product decreased the dissolution rate of OLZ, and the release rate kept sustained and stable, which was very suitable for sustained release and long-acting muscle injection formulations.

Real-world effectiveness of aripiprazole once-monthly REACT study: Pooled analysis of two noninterventional studies.

Noninterventional naturalistic studies are an important complement to randomized controlled trials. Aripiprazole once-monthly (AOM) is an atypical antipsychotic in a long-acting injectable formulation. A pooled analysis of two noninterventional studies was undertaken to validate previous results on AOM effectiveness and safety in a larger population and improve statistical power for preplanned subgroup analyses. We analyzed data from 409 patients with schizophrenia who were treated with AOM and were enrolled in noninterventional studies in Germany (via noninterventional studies registry 15,960 N) and Canada (NCT02131415). Data collected at baseline, 3 and 6 months were analyzed. Among the endpoints were psychopathology (brief psychiatric rating scale [BPRS]) and disease severity (clinical global impression [CGI]). Mean patient age was 38.9 (SD 14.8) years, and 59.9% were male. BPRS decreased from 48.1 (SD 15.6) at baseline to 36.5 (SD 13.7) at month 6 (p < 0.001). CGI decreased from 4.47 (SD 0.90) at baseline to 3.64 (SD 1.16) at month 6 (p < 0.001). A total of 54.4% were responders (at least 20% reduction) on the BPRS, and 56.5% had a CGI-S-score that was at least 1 level better than baseline. A total of 43.4% were considered responders on both the BPRS and CGI scales. A total of 45.2% were considered in remission. Adverse events were rare and corresponded to the previously known safety profile of AOM. Treatment with AOM for patients with schizophrenia appeared effective and safe under real-life conditions.

Can the use of long-acting injectable antipsychotic preparations be increased in routine clinical practice and the benefits realised?

Background:The use of continuing antipsychotic medication is an established evidence-based strategy for preventing relapse in people with schizophrenia, but medication adherence is known to be suboptimal. Covert non-adherence can be eliminated by the use of long-acting injectable (LAI) formulations. We sought to (1) raise awareness among clinicians of the potential benefits of LAI antipsychotic formulations, (2) increase use of these formulations for the treatment of schizophrenia in routine clinical practice and thereby (3) reduce the number of relapses requiring hospitalisation in patients with schizophrenia under our care.Method:Educational initiatives, promotion of reflective practice and patient-specific reminders were used to prompt increased use of LAI antipsychotic medication for patients with schizophrenia. Data relating to the use of these medications and the number of acute admissions for schizophrenia spectrum disorders (F20-29, ICD-10) over time were extracted from existing clinical information systems.Results:Over the 3-year time frame of our local initiative, the use of LAI antipsychotic preparations increased by 11%, the number of acute admissions for schizophrenia/schizoaffective disorder (F20 and F25) decreased by 26% and the number of acute bed days occupied by patients with these diagnoses decreased by 8%. The number of admissions for other psychosis diagnoses (F21-24 and F28-29) did not show the same pattern of improvement.Conclusion:In our health care organisation, raising clinicians’ awareness of the evidence base relating to the potentially favourable benefit–risk balance for LAI antipsychotic medication compared with oral formulations resulted in more use of the former. There were accompanying reductions in acute admissions and occupied bed days for patients with schizophrenia.

Real-life effectiveness of transitioning from paliperidone palmitate 1-monthly to paliperidone palmitate 3-monthly long-acting injectable formulation.

Non-adherence to antipsychotics in schizophrenia is associated with an increased risk of psychotic relapse and hospitalization, a risk that is reduced with the use of long-acting injectable (LAI) antipsychotics. Randomized clinical trials (RCTs) have demonstrated the efficacy of paliperidone palmitate 3-monthly (PP3M) for psychotic relapse prevention in schizophrenia, but it remains poorly documented among individuals treated in real-life settings who can benefit the most out of LAIs. The objective of this study was to evaluate the effectiveness of PP3M in relapse prevention among patients with schizophrenia. This is a multicentre retrospective study conducted in four outpatients' clinics across Canada. All consecutive patients with a main diagnosis of schizophrenia who initiated PP3M between June 2016 and March 2020 were included. The primary outcome was psychotic relapse, defined using broad and clinically relevant criteria. Among 178 consecutive patients who were switched to PP3M, the 12-month relapse rate was 18.5% and the relapse-free survival probability was 0.788 (95% confidence interval [CI] = 0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CI = 1.8-7.3, p < 0.001) and 3.1 (95% CI = 1.6-6.2), respectively. Increased psychopathology severity was associated with an increased likelihood of relapse, while having a job or being in school was protective. These findings reinforce the necessity of conducting research in patients with comorbid psychiatric disorders who are typically underrepresented in RCTs, yet overrepresented in real-life settings, in order to better inform and guide clinical practice.

Use of long-acting injectable antiretroviral agents for human immunodeficiency Virus: A review.

The development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the effectiveness of these medications depends upon consistent daily oral intake. Non-adherence can lead to the emergence of resistance, treatment failure and disease progression. This has necessitated the development of long-acting antiretroviral formulations administrable via an infrequent dosing regimen. Long-acting injectable forms of cabotegravir and rilpivirine have reached various stages in clinical trials both for the treatment and prevention of HIV. Other long-acting agents are at various stages of development. This review evaluates the current research on the development of long-acting injectable antiretroviral agents for the treatment and prevention of HIV.

Paliperidone palmitate depot microspheres based on biocompatible poly(alkylene succinate) polyesters as long-acting injectable formulations

The aim of this study was to design and evaluate biodegradable microspheres for the sustained delivery of Paliperidone Palmitate (PDP) towards the treatment of schizophrenia. The PDP-loaded microspheres were based on a series of five biocompatible poly(alkylene succinate)s, namely poly(ethylene succinate) (PESu), poly(butylene succinate) (PBSu), poly(hexylene succinate) (PHSu), poly(octylene succinate) (POSu), and poly(decylene succinate) (PDeSu), which were previously synthesized via a two-stage melt polycondensation method. Results showed that the molecular weight was higher (∼30-33k g/mol) for the polyesters synthesized using diols of lower molecular weight (PESu and PBSu), and significantly decreased (∼20k g/mol) for the three polyesters prepared with diols of higher molecular weight (PHSu, POSu and PDeSu). All polymers were of semi-crystalline nature and the melting temperatures were varying from 64.2 °C to 117.8 °C. The size of the PDP-loaded microspheres ranged from 20 to 50 μm, while XRD analysis revealed an encapsulated amorphous API. In vitro release studies revealed that PDP release is controlled by melting temperature of the polyesters. A detailed modeling analysis of the release curves was made to reveal the release mechanism. Overall results prove the suitability of the prepared polyesters to develop long-acting formulations that could enhance pharmacological effectiveness of the drug.

Efficacy of Long-Acting Bedaquiline Regimens in a Mouse Model of Tuberculosis Preventive Therapy.

Rationale: Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy. Objectives: The objectives of this study were to 1) determine the total duration of activity after an injection of long-acting bedaquiline and 2) evaluate the activity of regimens comprised of long-acting bedaquiline plus short (2-4 wk) oral companion courses of bedaquiline, with or without rifapentine, using the validated mouse model of tuberculosis preventive therapy. Methods: After the establishment of a stable Mycobacterium tuberculosis lung infection in bacillus Calmette-Guérin (BCG)-immunized BALB/c mice, treatment was initiated with 1 of 12 randomly assigned regimens. In addition to positive and negative controls, six regimens included one or two injections of long-acting bedaquiline (alone or with oral bedaquiline with or without rifapentine), and four comparator regimens consisted of oral agents only. Lung bacterial burden was measured monthly for up to 28 weeks. Measurements and Main Results: One injection of long-acting bedaquiline at 160 mg/kg exerted antituberculosis activity for 12 weeks. Compared with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bactericidal activity (including two all-oral comparator regimens), and two regimens had superior sterilizing activity: one injection with 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bedaquiline. Conclusions: Long-acting injectable bedaquiline has significant potential for shortening tuberculosis preventive therapy.

Development of Long-Acting Injectable Ketamine Loaded PLGA Microparticles as a Non-opioid Analgesic

Background/Objective: Ketamine, a psychedelic, is a noncompetitive N-methyl-D-aspartate receptor antagonist that may also bind to mu opioid receptors. Historically, it has been used as an anesthetic (KetalarÒ), although now has found uses as a novel, quick acting, antidepressant for treatment-resistant depression (SpravatorÒ) and could be used as an adjuvant to opioid analgesia providing opioid-sparing effects. One major advantage over opioids is Ketamine does not suffer from respiratory depression and maintains patent airways during anesthesia. Ketamine is only available as a short-acting injectable solution or a nasal spray. Our goal is to develop a long-acting injectable form in a biodegradable matrix poly(lactic-co-glycolic) acid (PLGA) that does not have a burst release and provides 5-7 days of steady-state plasma levels. &#x0D; Methods: A mechanistic approach towards development of a long-acting injectable began with a solubility screen of Ketamine. Based on these results, experiments began with an oil in water emulsification with two theoretical drug loadings (25% and 40%) and two processing conditions – (1) aqueous extraction and (2) aqueous extraction, intermediate drying, and a 25% Ethanol wash. The formulations were characterized for drug loading, drug release, and crystallinity and imaged using scanning electron microscopy (SEM). &#x0D; Results: Minimal differences were noted in the release profiles between formulations. Although, a significant difference was noted between the two processing conditions, where the extra intermediate drying step and 25% ethanol wash resulted in a significant slowing of the drug release rate. &#x0D; Conclusion and Implications: The difference in release kinetics is hypothesized to be due to densification of the PLGA matrix, based on the increase in surface roughness/wrinkling in the SEM images, crystallinity increase, and on their respective powder x-ray diffraction patterns. Our preliminary results demonstrate the feasibility of a longer acting Ketamine using PLGA. Further refinement of these formulations and rodent pharmacokinetic studies will be done in future.

P.0463 Phase 1 open-label study assessing the pharmacokinetics and safety of TV-46000, a novel long-acting subcutaneous injectable formulation of risperidone

P.0463 Phase 1 open-label study assessing the pharmacokinetics and safety of TV-46000, a novel long-acting subcutaneous injectable formulation of risperidone

Prospective analysis of serum prolactin levels, clinical symptomatology and sexual functions in patients with schizophrenia switched to paliperidone palmitate 3-monthly from paliperidone palmitate 1-monthly: Preliminary findings of the first 3 months.

Long-acting injectable (LAI) antipsychotics were developed to improve adherence to schizophrenia treatment. Paliperidone palmitate (PP) has two LAI forms: Monthly (PP1M) and three-monthly (PP3M). PP3M shows less difference in Peak-to-Trough drug concentration levels. This could be related to a lower incidence of hyperprolactinemia, which may negatively affect adherence. We aimed to compare prolactin levels and investigate relationships between prolactin levels, symptomatology and sexual function in patients with schizophrenia after switching from PP1M to PP3M. Twenty-five patients were enrolled. The sociodemographic data form, the Positive and Negative Syndromes Scale (PANSS) and the Arizona Sexual Experience Scale (ASEX) were used. Morning blood samples were drawn to determine prolactin levels. Prolactin level (p<0.001), the total score and arousal sub-score of ASEX (respectively; p=0.015, p=0.020) and the total score and positive scale of PANSS (respectively; p=0.017, p=0.021) were decreased on the 90th day (±15 days). After switching to PP3M, the decreases in prolactin levels and potentially related sexual side effects was statistically significant. There may be a difference between two formulations of the same drug in terms of side effects, and there is a need for prospective follow-up studies with larger samples.

Quality prescribing in early psychosis: key pharmacotherapy principles.

To present a practical, easy-to-implement clinical framework designed to support evidence-based quality prescribing for people with early psychosis. Identification and explanation of key principles relating to evidence-based pharmacotherapy for people with early psychosis. These were derived from the literature, practice guidelines and clinical experience. Key principles include (1) medication choice informed by adverse effects; (2) metabolic monitoring at baseline and at regular intervals; (3) comprehensive and regular medication risk-benefit assessment and psychoeducation; (4) early consideration of long-acting injectable formulations (preferably driven by informed patient choice); (5) identification and treatment of comorbid mood disorders and (6) early consideration of clozapine when treatment refractory criteria are met. Current prescribing practices do not align with the well-established evidence for quality pharmacotherapy in early psychosis. Adopting evidence-based prescribing practices for people with early psychosis will improve outcomes.

Initial Formation of the Skin Layer of PLGA Microparticles.

Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties have been adjusted to control the drug release kinetics and obtain desirable properties of PLGA-based drug delivery systems. The PLGA microparticle formation begins as soon as the drug/PLGA-dissolved in the organic solvent phase (oil phase) is exposed to the water phase. The initial skin (or shell) formation on the oil droplets occurs very quickly, sometimes in the matter of milliseconds, and studying the process has been difficult. The skin formation on the PLGA emulsion droplet surface that can affect the subsequent hardening steps is examined. PLGA droplets with different compositions are prepared. Using collimated light and a high-speed camera made it possible to detect the diffusion of acetonitrile from the oil phase into the water phase during the oil droplet formation. Although the skin formation is not visible on the surface of the oil phase droplet with the current setup, the droplet shapes, solid strand formation, and the difference in the spreading time suggest that the initial contact time between the oil and water phases in the range of a few seconds is critical to the properties of the skin.