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Long-acting injectable (LAI) antipsychotic medications can help improve treatment adherence in patients with schizophrenia and bipolar disorder. Despite this, they are underutilized. In 2003, intramuscular risperidone became the first available LAI atypical antipsychotic medication, and since then, a number of competing long-acting risperidone formulations have been brought to market, with additional options under active development. These include intramuscular, subcutaneous, long-acting oral, and implantable formulations. This review summarizes currently available and emerging long-acting risperidone formulations, including efficacy and safety data, and practical considerations aimed to help prescribers distinguish one formulation from another. There is an expanding number of currently available LAI antipsychotic medications giving patients and providers an opportunity to personalize and individualize care. Rates of adherence to treatment in patients with schizophrenia and bipolar disorder are low, and individualizing care can help improve this. The risperidone LAI treatment landscape includes five options approved by the U.S. Food and Drug Administration, with others under clinical development. These options differ in regard to mode of administration, approved indications, available dose strengths, injection intervals, needle size, injection volume, storage, and other variables. Prescribers should be familiar with these differing options to help patients find the best fit for their individual needs. [ABSTRACT FROM AUTHOR]

Dopamine β-hydroxylase (DBH) is a copper-containing enzyme that has an important role in maintaining the cellular homeostasis between the two neurotransmitters, dopamine (DA) and nor-adrenaline (NA). DBH functional polymorphisms are associated with multiple neuro-psychiatric conditions and are found to alter the DBH protein levels in serum affecting DBH enzymatic activity. The current study was conducted to determine the genetic and serum levels association of DBH rs1611115 functional polymorphism with major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SHZ) in the Pakistani population. In total n = 1097 subjects including MDD (n = 427), BD (n = 204), SHZ (n = 134) and healthy controls (n = 332), were screened for the functional polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression analysis was applied and the results were adjusted for age and sex. The DBH levels in serum were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied. The minor allele (-1021 C > T) was found to be significantly associated with a higher risk of developing BD and SHZ in both univariable and multivariable analyses. The overall total serum concentration of DBH was comparatively raised in MDD, however, in cross-comparison DBH serum levels were found markedly higher in CC homozygotes compared to TT homozygotes within the BD group. The present study suggested a significant association of DBH rs1611115 with BD and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BD for the first time in the Pakistani population. [ABSTRACT FROM AUTHOR]

Long-acting injectable antipsychotics (LAIs) are an effective, but potentially underutilized treatment option in schizophrenia and other severe mental illnesses. Prescribing information typically focuses on how to initiate treatment from the corresponding oral formulations. However, in clinical practice other scenarios, such as switching from other oral antipsychotics or other LAIs, occur frequently, requiring guidance. Pharmacodynamic properties of antipsychotics and their relation to rebound symptoms. Pharmacokinetic properties of LAIs and their implications for switching approaches. Specific approaches to switching to LAIs. The LAI landscape has evolved significantly in the last decade with more formulations available, longer dosing intervals, and extended indications. However, currently available LAIs have various shortcomings, e.g. short dosing intervals, need for oral supplementation, loading regimens, deep intramuscular injection and/or restricted indications. Recent improvements include a one-day initiation option for aripiprazole lauroxil, aripiprazole monohydrate once-monthly, risperidone in situ microparticles and subcutaneous risperidone. Future LAI developments should focus on longer dosing intervals, subcutaneous administration, expansion of LAIs beyond currently available antipsychotic agents and indications beyond schizophrenia and bipolar disorder. In the future, LAIs might become a first-line treatment after initial oral stabilization for chronic mental disorders with need for maintenance treatment and presence of significant non-adherence. [ABSTRACT FROM AUTHOR]

Schizophrenia usually begins with prodromal symptoms in adolescence. In 39% of patients, onset of psychotic symptoms occurs prior to age 19. Advances in the treatment of psychosis with medications over the last decade are reviewed in this paper. Understanding how to prescribe antipsychotics early in schizophrenia requires an understanding of the pathophysiology of the disease. The current structure of the dopamine hypothesis is reviewed. Risperidone, paliperidone, olanzapine, quetiapine, and aripiprazole have become established treatments prior to 2012. Since 2012, lurasidone (2017) and brexpiprazole (2022) have also been approved. Lurasidone was approved based on placebo-controlled studies, but brexpiprazole has been approved on the bases of open safety trials. In comparative trials, aripiprazole was better tolerated and less likely to cause hyperprolactinemia and metabolic abnormalities. Antipsychotics can induce adaptive changes in the brain that predispose patients to future problems such as tardive dyskinesia and supersensitivity psychosis. When pathophysiology of schizophrenia, and a clear understanding of the pharmacology of existing antipsychotics are included in the evidence-based analysis, use of partial agonists, which are less likely to induce adaptive changes in the brain and less likely to induce metabolic and prolactin side effects, become the preferred agents. [ABSTRACT FROM AUTHOR]

Risperidone has been significant correlated with a direct effect of interleukin-6 (IL-6) levels in patients with schizophrenia. This fact allows the opportunity to link the probable immunomodulatory effect of antipsychotic medication. Specially, a proper functioning of IL-6 pathway plays a potential role in the treatment or development of schizophrenia. Our primary aim was to perform a systematic review and meta-analysis to determine the effect of risperidone on IL-6 levels in individuals with schizophrenia. Studies were identified through a systematic search using PubMed, Scopus, and Web of Science databases. The articles found were subjected to the inclusion and exclusion criteria; then, the mean and standardised differences were extracted to calculate the standardised mean differences using the CMA software. IL-6 levels in individuals with schizophrenia were compared before and after receiving risperidone as treatment. Increased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone (point estimate 0.249, lower limit 0.042, upper limit 0.455, p-value 0.018). In the Asian population sub-analysis, no statistically significant differences were observed (point estimate 0.103, lower limit −0.187, upper limit 0.215, p value 0.890). When we compared individuals with schizophrenia to the control groups, a significant increase of IL-6 levels was observed in the group with schizophrenia (point estimate 0.248, lower limit 0.024, upper limit 0.472, p-value 0.30). Risperidone appears to play an important role in IL-6 levels in schizophrenia. Potential implications of increased IL-6 levels in people with schizophrenia should be considered in future studies. Increased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone. Risperidone appears to play an important role in IL-6 levels in schizophrenia. This study could serve for future research focussed on IL-6. [ABSTRACT FROM AUTHOR]

Background: The Smoke-free Policy represents a challenge in mental health services. Aim: To compare the stages of a smoke-free policy in a psychiatric hospital, according to the prevalence of smokers, hospital admission acceptance by hospitalized people, psychiatric complications, and the prescription of psychotropic drugs. Methods: Cross-sectional study was conducted with a comparison before and after implementing the Smoke-free Policy in a psychiatric hospital. Secondary data were obtained in 2020 from the medical records of 573 discharged people from psychiatric hospitalizations between September 2017 and August 2018. Fisher's exact test and the Kruskal-Wallis test were applied. Results: In the transition stage, there were more hospitalizations by court order, discharge motivated by the patient's disruptiveness behavior, administration of psychotropic drugs before the schedule time, physical aggression, physical/chemical restraints, length of stay, and dosage of psychotropic drugs. After the ban, there was a reduction in discharges motivated by the patient's disruptiveness behavior and an increase in discharge due to improvement in psychiatric symptoms, less occurrence of anticipation or modification in the use of psychotropic drugs, and fewer attempts to escape, aggressiveness, and physical restraint. Conclusion: The implementation of the Smoke-free Policy has a positive impact on psychiatric hospitalizations, with an increase in discharge due to improvement in psychiatric symptoms and a reduction in discharges due to other reasons. However, the transition stage requires greater attention from the nursing team, as the moment of adaptation to new rules and routines is followed by a momentary worsened behavior of those hospitalized. [ABSTRACT FROM AUTHOR]

Objectives: Schizophrenia is a devastating mental disease. Various microRNAs were proven to be associated with schizophrenia. Altered microRNA-144-3p (miR-144-3p) levels were found in various neurological and psychotic disorders. Beta2-subunit of Na(+)/K(+)-ATPase (ATP1B2) regulates neuronal migration and cell growth during brain development through the PI3K/Akt/mTOR pathway. The present study explored the associations of miR-144-3p and ATP1B2 with schizophrenia and their mutual interaction. Methods: A schizophrenic animal model employing repeated MK-801 administration was established and 293 T cells over-expressing miR-144-3p were constructed by lentivirus. The in vitro and in vivo levels of miR-144-3p, ATP1B2, and the PI3K/Akt/mTOR pathway were examined by qRT-PCR and Western Blots. The interaction between miR-144-3p and ATP1B2 was predicted and assessed by using bioinformatic methods and a luciferase reporter gene assay, respectively. Results: MiR-144-3p expression was elevated in the schizophrenic rat hippocampus. ATP1B2 was down-regulated in schizophrenic patients by analysing GEO datasets. Additionally, miR-144-3p can directly bind with ATP1B2. Furthermore, the ATP1B2 expression and PI3K/Akt/mTOR phosphorylation levels were down-regulated in the 293 T cells over-expressing miR-144-3p and schizophrenic rat hippocampus, which could be reversed by risperidone. Conclusions: This study revealed that up-regulated miR-144-3p might be associated with schizophrenia through down-regulating ATP1B2, implicating new targets of schizophrenia treatment. [ABSTRACT FROM AUTHOR]

Objective: Bupropion is one of the few medications with an FDA indication for smoking cessation. This is of particular significance due to the high co-morbidity of tobacco use disorder in patients with schizophrenia spectrum and other psychotic disorders. We sought to determine whether historical suggestions of bupropion's pro-dopaminergic activity lead prescribers to withhold bupropion in populations receiving antipsychotic medications. Methods: The prevalence in clinical practice of the combination of bupropion and 10 antipsychotic formulations was determined by a computer review of the Genoa Healthcare database for all prescribers at 10 participating community mental health centers. Actual prevalence was compared with expected prevalence using the test of proportions. A Bonferroni correction for multiple comparisons was included. Results: Clozapine, p = 0.0004, and the microsphere formulation of risperidone, p = 0.0045, were prescribed with bupropion significantly less often that chance. None of the other eight antipsychotic formulations were prescribed significantly differently than chance. Conclusions: The co-prescription of bupropion and antipsychotic medication may be affected by historical misconceptions regarding bupropion's purportedly pro-dopamine properties. Viable options for the treatment of tobacco use disorder should not be discounted prematurely in patients with schizophrenia spectrum and other psychotic disorders. We suggest further study on the safety and efficacy of the combination of bupropion and antipsychotic medication is needed. [ABSTRACT FROM AUTHOR]

Delusional infestation (DI) is a rare delusional disorder in which individuals have a false belief that they are infested with bugs, parasites, or insects, despite the lack of medical evidence that such an infestation exists. Data on the effectiveness of antipsychotics for DI are limited. We conducted a systematic review using EMBASE, MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials from inception of the databases up until July 20, 2018. Studies examining typical or atypical antipsychotics for primary DI were included. A total of 51 relevant articles were identified, primarily case reports/series. Overall response was favorable for both typical and atypical antipsychotics, but there was no strong evidence to suggest that any one antipsychotic agent was preferable to other agents. Pimozide (1–16 mg/day) and risperidone (0.5–8 mg/day) were the most commonly studied typical and atypical antipsychotics, respectively. Inconsistent reporting of treatment outcomes and variability in study designs limited the overall evaluation of the data. There remains a lack of sound data supporting the effectiveness of antipsychotic treatment for primary DI. Further research is required to establish more definitive conclusions about the relative clinical utility of antipsychotic agents for DI. [ABSTRACT FROM AUTHOR]

We report a case of late-onset schizophrenia that required differentiation from a dementing disorder. The patient was an 83-year-old woman who had experienced auditory hallucinations since she was 67 years old. The patient had slightly elevated total tau and slightly decreased amyloid β1-42, cerebrospinal fluid biomarkers. This case was identified as late-onset schizophrenia. However, the results of cerebrospinal fluid biomarkers indicated that neurofibrillary tangles and neuronal death, which are characteristic of Alzheimer 's disease, may also have been present. Late-onset schizophrenia should be treated based on an appropriate differential diagnosis, including neuropathological consideration of dementing disorders. [ABSTRACT FROM AUTHOR]

Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration. All patients (n = 226, mean age 34, females 33%) diagnosed with schizophrenia spectrum disorders (SSD; F20–F29) or other psychosis (F30-F32; F10-F19), were treated with olanzapine, quetiapine, risperidone or ziprasidone, and were assessed at baseline, 4-weeks, 14-weeks, and 27-weeks. The UKU-Side Effects Self-Rating Scale version was used to evaluate the side effect profiles, and the information on substance use was based on the Clinician Drug Use Scale. At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia. Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use. [ABSTRACT FROM AUTHOR]

Anticholinergic burden refers to the cumulative effect of medications which contain anticholinergic properties. We assessed how anticholinergic burden and different types of anticholinergic medications influence mortality rates among people with dementia in Northern Ireland. Our secondary aim was to determine what demographic characteristics predict the anticholinergic burden of people with dementia. Data were extracted from the Enhanced Prescribing database for 25,418 people who were prescribed at least one dementia management medication between 2010 and 2016. Information was also extracted on the number of times each available anticholinergic drug was prescribed between 2010 and 2016, allowing the calculation of an overall anticholinergic burden. Cox proportional hazard models were used to determine how anticholinergic burden influenced mortality whilst multilevel model regression determined what demographic characteristics influence overall anticholinergic burden. Of the 25,418 people with dementia, only 15% (n = 3880) had no anticholinergic burden. Diazepam (42%) and risperidone (18%) were the two most commonly prescribed drugs. Unadjusted Cox proportional hazard models indicated that higher anticholinergic burden was associated with significantly higher mortality rates in comparison to people with dementia who had no anticholinergic burden (HR = 1.59: 95% CI = 1.07-2.36). In particular, urological (HR = 1.20: 95% CI = 1.05-1.38) and respiratory (HR = 1.17: 95% CI = 1.08-1.27) drugs significantly increased mortality rates. People with dementia living in areas with low levels of deprivation had significantly lower anticholinergic burden (HR=-.39: 95% CI=-.47:-30). Reducing anticholinergic burden is essential for people with dementia. Further research should address the unfavourable prognosis of people living with dementia in highly deprived areas. [ABSTRACT FROM AUTHOR]

Considering the limitations of conventional risperidone (RSP) therapies, the present research characterizes the usefulness of multivesicular liposomes (MVLs) as an efficient controlled-release carrier for this widely used antipsychotic drug, to be employed for the treatment of schizophrenia. A 23 full factorial design based on three independent variables was implemented to plan the experiments: the molar ratios of lipid to the drug, triolein to phospholipid, and cholesterol to phospholipid. The impacts of these parameters on the risperidone encapsulation efficiency and its release pattern within the first 24 and 48 h were investigated as dependent variables. Then, the optimized liposomal system was further in-depth analyzed in terms of size, morphological and structural features, release profile over 15 days, biocompatibility, and stability. Optimized formulation parameters gave rise to MVLs possessing a spherical morphology with a median diameter of about 8 μm, a relatively narrow size distribution (span value of 1.49), and an encapsulation efficiency of 57.6%. These carriers not only exhibited a sustained-release behavior in vitro, lasting until the end of the 15 days but also underwent a negligible change in their size and RSP incorporation over two months at refrigerator condition. Furthermore, in vitro cytotoxicity and hemolysis assessments revealed that the optimized MVL formulation is biocompatible. This study revealed the potential of MVLs as a promising system for the delivery of RSP and could open a new vista for the successful management of schizophrenia. [ABSTRACT FROM AUTHOR]

Risperidone is a potent psychotropic agent has been approved for symptomatic treatment of irritability in children and adolescents with autism spectrum disorders. However, its bitter taste and dose adjustment of liquid dosage forms are a main hurdle for patient acceptance. Thus, this recent study investigate the formulation of taste masked risperidone orally disintegration minitablets (ODMT) as a way of enhancing patient acceptance. Taste masked risperidone hydrogenated castor oil or Cetyl alcohol based granules were prepared using a simple melt granulation technique in different drug to lipid ratios; drug release, bitterness score of the prepared granular formulations were evaluated. DSC was also performed to detect the possible drug lipid interaction. The selected lipid-based granules were further compressed into ODMT formulations. Bitterness score was assessed by gustatory sensation test and results were compared to marketed liquid formulations of risperidone. All the prepared ODMT formulations showed high content uniformity, with minimum dose fluctuation compared to marketed oral liquid preparations. In conclusion, risperidone lipid-based granules could be formulated in different ratios by simple techniques and commonly used excipients into taste masked risperidone ODMT with accurate and flexible doses suitable for pediatric use with high taste preference and acceptability. [ABSTRACT FROM AUTHOR]

Introduction: Antipsychotics are widely prescribed for patients with schizophrenia. The Brazilian public health system provides these patients free of charge to patients and it is pertinent to evaluate their benefits. Objective: To evaluate the effectiveness of olanzapine and risperidone in the treatment of patients with schizophrenia in the real-world and assessing risk factors for their discontinuation through a national non-concurrent cohort with 16 years of follow-up. Methods: Three SUS administrative databases were integrated by deterministic-probabilistic linkage. After patients were matched (1:1) for psychiatric hospitalization, year of receiving the antipsychotic, sex, and age, considering either olanzapine or risperidone at study entry. Kaplan-Meier was used to estimate the cumulative probabilities of discontinuation of treatment and associated factors were identified. Sensitivity analyses were performed. Results: 3416 pairs of patients were included. Olanzapine had a longer time until discontinuation of treatment (p = 0.021), and risperidone had a higher risk of discontinuation (p = 0.021). Among patients persistent for at least 24 months, there was no statistically significant difference. Conclusion: Olanzapine demonstrated superior real-world effectiveness over risperidone, in terms of survival and psychiatric hospitalization. This superiority was not sustained in all analyses. [ABSTRACT FROM AUTHOR]

Visual cortex functional deficits can be observed in schizophrenia patients and in individuals at high risk of schizophrenia. However, to date, few studies have investigated methods to improve these functional deficits. This study aimed to investigate the pathological change in the primary visual cortex of a prenatal MK-801-induced high-risk mouse model of schizophrenia (HRMMS) and to test the effect of paroxetine on visual cortex activity. Pregnant mice were given a systemic injection of MK-801, and male offspring that did not present schizophrenia-like behaviors in early adulthood were defined as HRMMS. Some of the HRMMS mice were treated with pharmacological agents beginning at 4 weeks of age. After 4 weeks of treatment with risperidone and/or paroxetine, two-photon calcium imaging was performed to analyze the primary visual cortex activity. The sucrose preference test and the prepulse inhibition (PPI) apparatus test were used to assess the cognitive and behavioral performance. HRMMS mice with or without risperidone treatment had impairments in the primary visual cortex as observed by reduced neuronal calcium activity. Risperidone plus paroxetine and paroxetine alone treatments increased the neuronal calcium activity in the primary visual cortex. Notably, the neuronal calcium activity was higher in mice treated with paroxetine alone. Treatment with paroxetine alone also improved the cognitive and behavioral performance better than treatment with risperidone plus paroxetine. Our pioneering animal model showed that treatment with paroxetine alone improves visual cortex impairments in HRMMS mice better than treatment with risperidone plus paroxetine, indicating that antipsychotics cannot normalize visual cortex impairments. [ABSTRACT FROM AUTHOR]

Schizophrenia and bipolar disorder are severe chronic neuropsychiatric diseases, affecting hundreds of millions of people worldwide. Asenapine maleate (ASM) has been demonstrated as a safe and effective therapeutic agent under twice-daily administration. However, lower compliance is observed when patients are treated with ASM, which significantly limits its application in schizophrenia and bipolar disorder. Moreover, the low bioavailability of ASM caused by first-pass metabolism and poor aqueous solubility also impairs the treatment effect. A formulation of ASM with the property of long-term sustained release and improved bioavailability can be a solution to overcome these weaknesses. In this article, we prepared ASM-loaded poly(lactic-co-glycolic acid) (ASM-PLGA) microspheres through different techniques, including emulsification-solvent evaporation (ESE), Shirasu porous glass membrane emulsification (SPG-ME), and microfluidic method. In vitro and in vivo assessments demonstrated that uniform-sized microspheres generated by the microfluidic process sustainably released ASM throughout 40-days, showing low burst release and significantly improved bioavailability. The results suggest that ASM-PLGA microspheres prepared by the microfluidic method provide an efficient strategy to enhance the drug exposure of ASM as the treatment of chronic neuropsychiatric diseases. It is also evident that this microfluidic strategy has the potential to construct with other drugs, establishing long-acting formulations. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to explore the anti-inflammatory potential of risperidone in acetic acid-induced rat colitis through inhibition of TLR4/NF-kB pathway. Acute colitis induction was done by intra-rectal administration of 2 mL of 4% diluted acetic acid solution. Two h after colitis induction, dexamethasone (2 mg/kg) as standard drugorrisperidone (2, 4 and 6 mg/kg) were administered orally to wistar rats for five consecutive days. 24 h after the last treatment, animals were sacrificed by cervical dislocation. Macroscopic and microscopic damage evaluation was done. Biochemical and ELISA methods were used to assess myeloid peroxidase (MPO) enzyme activity and tumor necrosis factor-α (TNF-α) level respectively. Moreover, immunohistochemistry (IHC) was performed to detect the expression of TLR4 and pNF-kBproteins. Dexamethasone (2 mg/kg) or risperidone (2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic (p <.001) and microscopic lesions. Additionally, risperidone (2, 4 and 6 mg/kg) inhibited the activity of MPO and TNF-α (p <.01, p <.001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone (2, 4 and 6 mg/kg) significantly reduced acetic acid-induced expression of TLR4and pNF-kB proteins (p <.05, p <.01, p <.001). The anti-inflammatory effect of risperidone on acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway. [ABSTRACT FROM AUTHOR]

The majority of patients with delusional infestation (DI) seek help from dermatologists as they consider their condition to be of cutaneous origin and deny referral to psychiatrists, with the prevalence of the condition arising. The objectives of our study were: (i) to assess whether there is a fixed delusional ideation in patients with DI, (ii) to assess the efficacy of managing such patients with combined dermatological and psychiatric treatment and (iii) to test any correlation between BABS scores and other variables. All consecutive newly diagnosed patients with DI, from January 2014 to January 2015, seen in our specialist psychodermatology clinic were enrolled in our prospective observational study. Brown Assessment of Beliefs Scale (BABS) was used to assess the intensity of delusion. Correlation between BABS and other variables was also assessed. Forty-three patients were enrolled. There was a range of BABS scores pre- and post-treatment, indicative of the presence of a range of delusional ideation. A significant reduction in the BABS scores was noted post-treatment from 16.10 ± 5.53 to 11.66 ± 8.26 (p <.002). This is the first study to objectively demonstrate that delusional belief in patients with DI is not a binary phenomenon and to demonstrate an efficacious response to a combined multidisciplinary psychodermatological approach. [ABSTRACT FROM AUTHOR]

This study reports a novel heart-cutting two-dimensional high performance liquid chromatography (2D-LC) method with ultraviolet detection for the determination of risperidone and 9-hydroxyrisperidone in human serum. In this 2D system, a strong cation-exchange column was applied for the first dimensional (1D) separation to isolate the targets from the complex serum matrices, and a middle column was used to transfer the targets from the first dimension to the second dimension (2D) through a six-port valve. A reverse-phase C18 column was selected in the second dimension for further separation. An assistant pump was optimized to prevent the peak dispersion and the loss of resolution. This method has the advantages of high sensitivity by large injection volume, simple one-step sample preparation and short analysis time. A linear range between 5 and 146 ng/mL for risperidone and 7 and 200 ng/mL for 9-hydroxyrisperidone was achieved. All of the results showed that the coupling of ion-exchange with reversed-phase liquid chromatography had powerful separation capabilities for risperidone and 9-hydroxyrisperidone in human serum. The method exhibited good repeatability and recoveries and may be used as a reliable approach for therapeutic drug monitoring in clinical analysis. [ABSTRACT FROM AUTHOR]

Objective: To address gaps in the literature on healthcare resource utilization (HRU) and costs among patients with schizophrenia and prior hospitalization who transition from oral risperidone or paliperidone (oral ris/pali) to once-monthly paliperidone palmitate (PP1M) in a real-world setting by comparing treatment patterns, HRU, and costs 12-months pre- and post-transition to PP1M among Veterans Health Administration (VHA) patients affected by schizophrenia who have had ≥1 hospitalization. Methods: VHA patients with schizophrenia (aged ≥18 years) who initiated oral ris/pali, had ≥1 all-cause inpatient stay, and transitioned to PP1M from January 2015–March 2017 were included from the VHA database. The first transition date to PP1M was identified as the index date. Patients were required to have continuous health plan eligibility for 12 months pre- and post-PP1M. Outcomes were compared using the Wilcoxon signed-rank and McNemar's test, as appropriate. Results: The study included 319 patients (mean [SD] age = 51.6 [4.2] years) during 12 months of baseline and follow-up. During pre-PP1M transition, 7.2% of the patients were adherent (proportion of days covered [PDC] ≥ 80%) to oral ris/pali. Post-PP1M transition, 27.6% of the patients were adherent to PP1M. Comparison of HRU outcomes from the pre- to post-PP1M transition revealed significantly lower all-cause inpatient stays (3.5 vs 1.4, p <.0001) and shorter inpatient length of stay (43.4 vs 18.3 days, p <.0001). Similar trends were seen for mental health and schizophrenia-related HRU. Cost outcome comparison indicated significantly lower all-cause inpatient costs ($64,702 vs $24,147, p <.0001), total medical costs ($87,917 vs $56,947, p <.0001), and total costs ($91,181 vs $69,106, p <.0001). A similar trend was observed for mental health and schizophrenia-related costs. Conclusions: Transitioning from oral ris/pali to PP1M may significantly improve HRU and provide potential cost savings in VHA patients with schizophrenia and ≥1 prior hospitalization. [ABSTRACT FROM AUTHOR]

Postictal psychosis (PIP) in patients with epilepsy is often mistaken for other primary psychiatric disorders. Depending on its severity, PIP often prompts empiric treatment with atypical antipsychotics, which are balanced against the risk of lowered seizure thresholds. Here we present a case of olanzapine-resistant PIP, where risperidone was used as a safe and effective abortive treatment. [ABSTRACT FROM AUTHOR]

Objectives: Hyperprolactinemia (HPRL), defined as plasma prolactin (PRL) >25 ng/ml, is a frequent adverse effect of the treatment with some antipsychotics. The objectives of this study were to determine the prevalence of HPRL among schizophrenic patients treated with long-acting injectable (LAI) antipsychotic drugs at our hospital, and to estimate gender effects in PRL levels in these patients. Methods: This cross-sectional, retrospective, study analyzed 165 psychotic patients treatment with LAI antipsychotics in monotherapy from February to May of 2017 at the Psychiatry Specialized Care Units of the Elche General Hospital (Spain). Results: The prevalence of antipsychotic-derived HPRL in our hospital was 52.41%. Patients treated with LAI formulations of paliperidone and risperidone presented the highest levels of HPRL. A linear regression model showed that female patients presented 24.95 ng/ml (CI95 = 16.85, 33.05) higher levels of PRL than male patients (p <.0001). For women, age >45 years was associated to reduced levels of PRL with respect to younger patients (mean= −18.86 ng/ml, CI95 = −35.59, −2.13, p <.05). Conclusions: Our study confirmed the effects of LAI paliperidone and risperidone on PRL levels. Sex and age were significantly associated with PRL levels in patients treated with LAI antipsychotics, with younger women presenting higher rates of HPRL than men. HPRL is a common adverse effect of the treatment with antipsychotics, detectable in over half of the patients treated in our hospital. Our study showed that treatment with LAI formulations of paliperidone and risperidone resulted in the highest levels of HPRL. Sex and age were significantly associated with PRL levels in patients treated with LAI antipsychotic drugs, with younger women presenting higher rates of HPRL than men. [ABSTRACT FROM AUTHOR]

Objective: High lipophilicity and extensive hepatic metabolism limits the oral application of risperidone in the treatment of CNS disorders. In order address this limitation, risperidone (RS) loaded chitosan nanoparticles (CS-NPs) were processed for intranasal administration in the management of schizophrenia. Methods: RS loaded CS-NPs were prepared by ionic gelation of chitosan with tripolyphosphate and stabilized by tween 80/ poloxamer 188. The CS-NPs were characterized by FTIR, DSC, particle size, zeta potential and surface morphology. Entrapment efficiency, mucoadhesive strength, in vitro drug release, and release kinetics of CS-NPs were evaluated. Pharmacokinetics and pharmacodynamics of RS loaded CS-NPs were studied using Wistar rats. Stereotypy behavior and swimming normalization tests were conducted in amphetamine induced psychosis in animals. Results: Risperidone nanoparticles (RP12) were produced with an average size of 86 nm, polydispersity index of 0.287, zeta potential of +36.6 mV, mucoadhesion of 68.9% and entrapment efficiency of 77.96%. CS-NPs released the RS in controlled manner with Fickian diffusion mode. Maximum concentration of RS in plasma was 1240 ng/ml at 4 h for RP12, and 403.8 ng/ml at 2 h for RS sample. RS loaded CS-NPs significantly reduced the stereotypy score in experimental animals that indicated the efficiency of CS-NPs in delivery of RS at brain tissues and moreover amphetamine effect was reversed. Thus, RS loaded CS-NPs proved as potential delivery systems against induced psychotic disorders. Conclusion: Risperidone loaded chitosan nanoparticles were effective against schizophrenia via intranasal route. [ABSTRACT FROM AUTHOR]

Objectives: To describe clinical consequences of risperidone medication errors in children of less than 13 years and to estimate a clinically relevant toxic dose. Methods: All cases of risperidone medication errors managed by French Poison Centres from 2001 to 2012 were analyzed. Inclusion criteria were a delay of at least 2 hours between ingestion and request to the FPC in asymptomatic children, an ingested dose above two-fold the maximal daily dose for children above 5 years or any symptomatic patient at the time of first contact. Results: One hundred and sixty cases met our criteria. Median age was 8 years (range 0.9–12) and 28.1% were aged 5 years or less. Causes of the error were an incorrect dose in treated children (84.2%) or a dose given to a wrong child (15.8%). The median ingested dose was 0.1 mg/kg or 3.3-fold the maximum recommended dose. Overall, 59 children had no symptoms, 95 experienced minor symptoms and six moderate symptoms. Somnolence/sedation was the most common (73.3%). Of the 17 children who developed extrapyramidal disorders, all had minor or moderate symptoms and only five required a symptomatic treatment. Conclusions: Risperidone medication errors in children cause minimal effects. Somnolence and mild to moderate extrapyramidal reactions were the main features of toxicity, and significant cardiac or other neurological features were not observed. No case with severe toxicity was noted. At home surveillance can be proposed for children exposed to a dose ≤0.15 mg/kg. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the influences of drying methods on the risperidone (RIS) release profiles of RIS-loaded PLGA microspheres. These microspheres were fabricated with an O/W emulsion solvent evaporation method. The wet microspheres were dried with freeze drying and vacuum drying methods. The microspheres were mono-dispersed spheres with an average diameter of 100 μm. Studies found that drying methods had great influence on the porosity, morphology, and release profiles of RIS-loaded PLGA microspheres. Specifically, the freeze-dried microspheres had higher porosity (78.46 ± 1.64%) than those vacuum-dried ones (52.45 ± 2.68%), and they showed higher RIS release rates (p < 0.05). In the accelerated release tests (45 °C), these microspheres dried under the pressures of 700 mmHg and 200 mmHg gave faster release rates than those ones dried under the pressure of 450 mmHg. Importantly, the accelerated release test (45 °C) had a high correlation with the real-time test (37 °C) (R2 > 0.99). These studies exhibited a significance in the precise preparation of RIS-loaded PLGA microspheres. [ABSTRACT FROM AUTHOR]

Mephentermine is an α-adrenergic agonist, indicated for treatment of hypotensive states. It is not a common drug used for recreational purposes; rather for its performance enhancing properties. However, there are few case reports which highlight its dependence potential or its effect on induction of psychotic symptoms. In this case series, we intend to present cases of two individuals who used mephentermine as performance enhancer. Both showed significant improvement in short span of time on remaining abstinent from it. This highlights the common context of usage of mephentermine as performance enhancer leading to dependence and its effect on induction of psychosis in individuals with low genetic vulnerability. [ABSTRACT FROM AUTHOR]

Objective: In the present work nanocrystal-based formulation of risperidone (RIS) was proposed to overcome solubility issue of RIS, while lyophilization technique was used effectively, for conversion of RIS nanosuspension to solid state. Significance: RIS nanosuspension was developed and stabilized with a combination of polycaprolactone and Pluronic® F-68 as stabilizers. With focus on critical parameters like nature of cryoprotectants and effect of eutectic temperature on properties of nanosuspension, the suitability of lyophilization technique in improving the physical stability of prepared nanosuspension was also evaluated. Additionally, the developed nanocrystals were also assessed for their solid states properties. Methods: Various process parameters affecting average particle size and polydispersity index (PDI), viz. drug to surfactant ratio, solvent to anti-solvent ratio, stirring speed, type of stabilizer were optimized. Assessment of lyophilization as a suitable solidification technique (for conversion to powder form) was done with selective cryoprotectants (trehalose dihydrate and sorbitol). Results: The formulation was found to be stable at 4 °C for 3 months with size, PDI and zeta potential of 214 ± 3.4 nm, 0.120, and -10.2 ± 0.90 mV, respectively. Release profile of developed nanosuspension showed cumulative % release of ∼90% in initial 10 h whereas the value for the unprocessed drug was ∼11% in same time frame. Conclusions: These findings suggest that developed formulation was able to enhance water solubility of the drug effectively and can be potentially used in the management of psychotic disorders. [ABSTRACT FROM AUTHOR]

Introduction: This article includes a combined analysis of therapeutic drug monitoring (TDM) studies and a review of the marketer’s data on pharmacological mechanisms. Areas covered: An article search led to the inclusion of 21 paliperidone studies in the systematic review plus 2 case reports. Paliperidone clearance was calculated from: 1) steady-state studies using concentration/dose (C/D) ratios, and 2) single-dose studies describing 24-h area under the curve calculations. The marketed extended-release formulation has 28% bioavailability. Calculated mean C/D ratios (ng/ml/mg/d) were: 1) 4.09 in 6 studies of 221 non-Korean and non-geriatric adult patients, 2) 2.59 in 2 studies of 100 Korean adult patients, and 3) 6.89 in 1 study with 15 elderly Japanese patients. The limited drug-drug interaction studies indicated that carbamazepine is a clinically relevant inducer requiring three times the dosage, and that valproate, probably an inhibitor, requires half the dosage. Renal impairment markedly decreased paliperidone elimination, and other antipsychotics should be considered. Expert Commentary: We recommend more use of: 1) paliperidone TDM in clinical practice, 2) TDM when moving from oral to long-acting paliperidone, 3) better designs for paliperidone TDM studies, 4) laboratory studies on paliperidone pharmacokinetic mechanisms, and 5) TDM studies comparing paliperidone and risperidone dosing. [ABSTRACT FROM AUTHOR]

Angioedema has recently been reported as a side effect associated with the antipsychotic risperidone. We report a case of dystonia with concurrent angioedema due to risperidone. A 40-year-old male with a history of schizophrenia was started on 3 mg of risperidone BID and developed perioral and periorbital edema along with increased muscle rigidity and hand tremor within 24 h of initial administration. His symptoms abated after cessation of risperidone and intravenous administration of corticosteroids and antihistamine. This case study adds to the current literature, which has already established angioedema as a dose-dependent side effect of risperidone. Moreover, this case study aims to increase awareness about the potential for the simultaneous occurrence of angioedema and extrapyramidal symptoms, and promotes vigilance among prescribers so that the life-threatening consequences of such effects can be avoided. [ABSTRACT FROM AUTHOR]

The principal objective of the present study is to achieve a depot formulation of Risperidone by gelation of silk fibroin (SF). For this purpose, hydrochloric acid (HCl)/acetone-based and methanol-based hydrogels were prepared with different drug/polymer ratios (1:3, 1:6, and 1:15). For all the drug-loaded methanol-based hydrogels, gel transition of SF solutions occurred immediately and the gelation time was 1 min, while the gelation time of HCL/acetone-based hydrogels was around 360 min. According to the results obtined from Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectra, solvent systems and Risperidone could induce β-sheet structure, but HCL/acetone system had the lowest effect on induction of β-sheets. The crystallinity was increased by increasing the amount of Risperidone, and drug to polymer ratio of 1:3 possessed the highest crystallinity. Thermogravimetric analysis (TGA) indicated that increasing the amount of drug in formulation increased the stability of hydrogels, and methanol-based hydrogel with a ratio of 1:3 had the most stable structure. The release rate of Risperidone from methanol-based hydrogel at ratio of 1:3 was lower than that for HCl/acetone-based one, and it decreased by increasing the amount of Risperidone. The release of Risperidone from methanol hydrogel at ratios 1:3 and 1:6 continued up to 25 d which is acceptable for depot form of Risperidone and shows that the extended release of Risperidone was achieved successfully. In conclusion, SF hydrogel with the ability to respond to the environmental stimuli is an excellent candidate for injectable implants for extended release of Risperidone. [ABSTRACT FROM PUBLISHER]

Antipsychotics have been the mainstay of the treatment of schizophrenia, and their potential role in neuroprotection could be related to brain-derived neurotrophic factor (BDNF). So far different effects on both serum and plasma levels of BDNF were reported related to the various antipsychotic treatments. Aim of this study was to investigate the influence of olanzapine or risperidone on both plasma and serum levels of BDNF in patients with acute schizophrenia. For 50 participants with acute episode of schizophrenia both plasma and serum BDNF, along with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale, were assessed pretreatment and post treatment -- after 6 weeks of either risperidone or olanzapine. Results show that a weak correlation between pre-treatment plasma and serum levels of BNDF was found no longer significant after 6 weeks of treatment. Antipsychotics, olanzapine and risperidone showed no significant effect on post treatment plasma and serum levels of BDNF. Pretreatment plasma level of BDNF and PANSS positive subscale were positively correlated. Post treatment serum level of BDNF and Clinical Global Impression were negatively correlated. In conclusion, plasma and serum BDNF levels could be different markers to some extent with regard to clinical symptoms, response to therapy and outcome. The interrelation between serum and plasma BDNF should be established in further studies. [ABSTRACT FROM AUTHOR]

The aim of the present study is to prepare risperidone-loaded poly lactic-co-glycolic acid (PLGA) microspheres within microfluidic system and to achieve a formulation with uniform size and monotonic and reproducible release profile. In comparison to batch method, T-junction and serpentine chips were utilized and optimizing study was carried out at different processing parameters (e.g. PLGA and surfactant concentration and flow rates ratio of outer to inner phase). The computational fluid dynamic (CFD) modeling was performed, and loading and release study were carried out. CFD simulation indicates that increasing the flow rate of aqueous phase cause to decrease the droplet size, while the change in size of microspheres did not follow a specific pattern in the experimental results. The most uniform microspheres and narrowest standard deviation (66.79 μm ± 3.32) were achieved using T-junction chip, 1% polyvinylalcohol, 1% PLGA and flow rates ratio of 20. The microfluidic-assisted microspheres were more uniform with narrower size distribution. The release of risperidone from microspheres produced by the microfluidic method was more reproducible and closer to zero-order kinetic model. The release profile of formulation with 2:1 drug-to-polymer ratio was the most favorable release, in which 41.85% release could be achieved during 24 days. [ABSTRACT FROM PUBLISHER]

Introduction: This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was 0.48 (approximately twice that of oral risperidone TDM) in a combined analysis from 329 patients in 6 risperidone LAI studies without major confounders. The total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4 to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary: Clinicians using TDM for risperidone LAI microsphere formulation need to: 1) consider steady state to be reached ⩾ 6 weeks after the first injection, 2) pay attention to a) comedications with inducers/inhibitors, b) severe inflammations/infections and c) hepatic/renal impairment and 3) use Castberg's recommendation to calculate risperidone dosing. [ABSTRACT FROM AUTHOR]

Risperidone is an atypical antipsychotic that is active at multiple dopamine and serotonin receptor subtypes. Based on its high affinity for serotonin receptors, we predicted that it might reset circadian rhythms in a nocturnal rodent. We report temporally differentiated and differential effects of various doses of risperidone on the voluntary locomotor activity rhythm in the Indian field mice,Mus booduga. Risperidone (0.5 mg/kg) elicited phase delays at phases between CT (circadian time) 12 to CT18 and CT0 to CT3, and phase advances at CT6, CT9 and CT21. However, mice injected at CT6 showed maximum advances (1.299 ± 0.286 h), whereas at CT15 showed maximum delays (−1.514 ± 0.312 h). Increasing the dose beyond 0.5 mg/kg at maximally responsive CTs (CT6 and CT15) resulted in progressively smaller but significant shifts. Thus, 0.5 mg/kg is the optimal dose in this species. The fact that risperidone resets the circadian rhythm in a mammal can be extended to clinical studies and used for optimal adjustment of the circadian rhythm in mental disorders. Conversely, risperidone administration for various treatments must be carefully timed to prevent unwanted phase shifts in patients. [ABSTRACT FROM PUBLISHER]

Objective: To compare adherence with lurasidone to other oral atypical antipsychotics among Medicaid and commercially insured patients with schizophrenia.Research Design and Methods: Administrative claims of patients with schizophrenia treated with atypical antipsychotics (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) from October 2010 to September 2011 were identified from MarketScan Commercial and Medicaid Databases, and were classified by the first (index) antipsychotic. Patients were 18-64 years, had insurance coverage 12 months pre- and 6 months post-index, and no pre-index use of the index drug.Main Outcome Measures: Medication possession ratio (MPR), discontinuation rate, and mean time to discontinuation were assessed post-index. Pairwise comparisons (lurasidone versus each drug) were conducted using chi-square tests and Student's t-tests.Results: There were 146 Medicaid (mean age 43.5 years, 47.9% female) and 63 commercial (mean age 40.0 years, 42.9% female) patients treated with lurasidone. In the Medicaid population, the MPR for patients treated with lurasidone was 0.60, versus 0.41-0.48 for patients treated with other antipsychotics (all p < .05). Patients treated with lurasidone exhibited a lower discontinuation rate compared to patients treated with all other antipsychotics (49.3% versus 62.3%-68.3%, all p < .05). The mean time to discontinuation with lurasidone was significantly longer than with ziprasidone (p < .05). In the commercial population, the MPR for patients treated with lurasidone (0.61) was higher compared to patients treated with quetiapine (0.44) and ziprasidone (0.43) (both p < .05). The discontinuation rate (44.4%) was lower for patients treated with lurasidone compared to patients treated with all other antipsychotics except risperidone (p < .05). The mean time to discontinuation was longer for lurasidone than with other antipsychotics.Conclusions: In Medicaid and commercial populations, patients treated with lurasidone demonstrated greater adherence compared to patients treated with other atypical antipsychotics. Limitations of using administrative claims data include potential errors or inconsistencies in coding, and lack of complete clinical information. [ABSTRACT FROM AUTHOR]

Background and aims: Dual diagnosis commonly occurs among patients with an opioid use disorder. Treatment is ideally performed in an integrated fashion. We present a case that illustrates the complex and challenging psychiatric and medical therapy of such patients in the light of the literature.Case description: We report on a 56-year-old patient with schizophrenia and opioid dependence who experienced both risperidone-induced Pisa syndrome and, 3 years later, acute psychosis after switching the opioid substitution medication from methadone to slow-release oral morphine due to QT prolongation.Conclusions: With the current availability of a diversity of substitution opioids in Switzerland (methadone, buprenorphine, diacetylmorphine, sustained-release oral morphine), studies on differential effectiveness of these agents in opioid-dependent subpopulations with selective comorbidity profiles are desirable. The same is true for further investigation of the involvement of the opioid receptor system in schizophrenia. In clinical practice, any alteration of opioid medication in patients with dual diagnosis and a history of schizophrenia should be accompanied by close observation for psychotic symptoms. [ABSTRACT FROM PUBLISHER]

The aim of this study was optimization of risperidone (model drug) biodegradable nanoparticles utilizing emulsion–solvent evaporation technique. Box–Behnken design was adopted to optimize the preparation process. Optimized nanoparticles were characterized for surface morphology using scanning electron microscope. Pharmacokinetic parameters were compared with the marketed tablets. Results revealed that the optimized formula showed 297.37 nm, 85.12%, and 59.79% for Y1, Y2, and Y3, respectively. Optimized formula showed significant improved bioavailability compared with marketed tablets. Successful achievement of prolonged risperidone release with improved bioavailability is expected to maximize patients’ adherence to their antipsychotic drug therapy and to minimize risk of relapse during maintenance therapy. [ABSTRACT FROM AUTHOR]

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10–30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE25, MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cpmax, respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability. [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]

Context: The oral delivery of risperidone encounters a number of problems, such as pH dependent solubility and low bioavailability, due to its lipophilicity and aqueous insolubility. Objective: To improve the solubility, dissolution and intestinal permeation thereby bioavailability of risperidone through a novel self-nanoemulsifying powder (SNEP) formulations. Materials and methods: Oleic acid, Tween® 20, PEG 600 and Aerosil® 200 were chosen as oil, surfactant, co-surfactant and carrier, respectively from solubility and emulsification studies. Ternary phase diagram was constructed to determine emulsifying region. Results and discussion: The Z-average and polydispersity Index of developed formulation was 83.1 nm and 0.306, respectively. Ex vivo permeation studies on isolated rat intestine indicated that the amount of risperidone permeated from SNEP formulation was increased around 4- and 1.8-fold than that of pure drug and marketed formulation, respectively. Conclusion: This developed SNEP formulations can be regarded as novel and commercially feasible alternative to the current risperidone formulations. [ABSTRACT FROM AUTHOR]

The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicityin vivoand inin vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation. All of these effects were significantly (p < 0.05) inhibited by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Similar outcomes were obtained from thein vivoexperiments. Liver function enzyme test and histopathological evaluation confirmed RIS-(6 mg/kg) induced damage. Based on these results, it is suggested that RIS-induced liver toxicity is associated with mitochondrial/lysosomal cross-talk following the initiation of oxidative stress. Thus, the use of CoQ10 and/or NAC seems to be a safe therapeutic option in this context. [ABSTRACT FROM AUTHOR]

The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release bothin vitroandin vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95 ± 18.88 µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (Cmax = 110.1 ±54.2 ng/ml) and subsequent slow drug release (Cs(4–54d)= 2.7 ± 0.8 ng/ml)in vivo. Small microspheres (5.91 ± 2.24 µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (Cmax = 40.9 ± 13.7 ng/ml), whereas the drug release rate from 4 to 54 d was increased (Cs(4–54d)=4.1 ± 1.0 ng/ml). By further decreasing the size of microspheres to 3.38 ± 0.70 µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce thein vivoburst release of SAIB system alone. [ABSTRACT FROM PUBLISHER]

Introduction:Long-acting injectable antipsychotics (LAIAs) were introduced to improve treatment adherence and tolerability of oral formulations. After risperidone was introduced as the first long-acting injectable second-generation antipsychotic, during the last five years olanzapine pamoate, once-monthly paliperidone palmitate and once-monthly aripiprazole has also been marketed. Areas covered:A three-month injection of paliperidone palmitate (3MPP) was introduced in the North-American market in 2015. It will be gradually available in the rest of the world in the coming years. The principal aim of this review is to evaluate its efficacy and tolerability and to discuss the possible role it may play. Expert commentary:In the coming years an increase in the prescription rates of LAIAs is expected. 3MPP offers a substantially longer dosing interval than other options, which may be a potential advancement to reduce nonadherence. Future research and experiences will identify which subpopulation may obtain greater benefit from this new tool. [ABSTRACT FROM PUBLISHER]

Objective: To investigate the correlation between insight and recovery in schizophrenic patients according to criteria for both symptomatic and functional remission.Methods: Seventy patients affected by paranoid schizophrenia were recruited and treated with olanzapine, risperidone, aripiprazole, haloperidol and ziprasidone; visits were scheduled at baseline, 12 and 36 months. We administered PANSS (Positive and Negative Syndrome Scale), GAF (Global Assessment of Functioning), SF-36 (Short Form 36 Health Survey), PGWBI (Psychological General Well-Being index) and SAI (Schedule for the Assessment of Insight).Results: After 1 year, 50% of the subjects obtained symptom remission and 25.5% had adequate social functioning for 2 years or more. Only 12% of subjects met full recovery criteria for 2 years or longer. The recovery group also showed an improvement in insight levels, especially patients treated with second-generation antipsychotics (SGA). Recovery was predicted by female sex, higher age, SGA treatment, pre-morbid social adaptation and low level of negative symptoms at baseline.Conclusions: Only a small proportion of schizophrenic patients achieved recovery, therefore greater patient’s insight could have prognostic validity in terms of treatment outcome. More sensitive instruments and a larger sample are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

The paper is devoted to the investigation of the effect of polyester hydrophobicity and ability for crystallisation on lipophilic drug loading and release from microparticles fabricated on the base of these polymers. Poly(l-lactic acid), poly(d, l-lactic acid) and poly (lactic acid-co-glycolic acid) were synthesised by ring-opening polymerisation using stannous octoate as catalyst, while poly(caprolactone) (PCL) and poly(ω-pentadecalactone) (PPDL) formation was catalysed by lipase. The particles were formedviasingle emulsion evaporation/diffusion method. The particles obtained were studied using SEM, XRD and DSC methods. The degradation of particles based on different polyesters, entrapment and release of a model hydrophobic drug (risperidone®) were thoroughly studied. The effect of particles hydrophobicity and crystallinity on these parameters was of most interest. The drug entrapment is greater for the hydrophobic polymers. Drug release was more rapid from crystalline particles (PLLA, PCL, PPDL), than from amorphous PDLLA and PLGA ones. [ABSTRACT FROM PUBLISHER]

Reported here is the case of a 41-year-old female who developed paranoia and delusions. Physical examination, laboratory studies, and neuroimaging were unremarkable. She was diagnosed with schizophrenia and treated with risperidone, ultimately at a dose of 3 mg daily, with improvement. Her EEG showed bursts of 30–40 Hz gamma activity in the frontal regions, a finding sometimes noted on the resting EEGs of patients with schizophrenia. This report discusses gamma activity as well as other EEG abnormalities that may occur on the resting EEG of patients with schizophrenia. Additionally discussed is recent research suggesting that 35–45 Hz gamma activity associated with active information processing and cognition may be decreased in patients with schizophrenia compared to normal individuals. The role of gamma activity, both in the resting state and during cognitive activity, could be an area of importance for future research in schizophrenia and possibly other disorders. [ABSTRACT FROM PUBLISHER]

An ABA-type triblock copolymer was synthesized through group-transfer polymerization by using poly[2-(diethylamino) ethyl methacrylate] (PDEA) as A block and poly[2-(dimethylamino) ethyl methacrylate] (PDMA) as B block. By utilizing the 1,3-propane sultone to obtain polyzwitterionic triblock copolymer under moderate conditions, PDMA block of the triblock copolymer has been selectively betainized. The selectively betainized block copolymer and its precursor were molecularly dissolved in acidic aqueous media without any use of cosolvent at room temperature. In both cases, an increase in solution pH caused near monodisperse cationic or neutral flower-like micellization with hydrophobic PDEA-core at basic aqueous solution. However, at higher polymer concentrations where precursor triblock copolymer does not exhibit any gelling behavior (10% and higher), polyzwitterionic copolymer derivative can be gelated as a result of inter-chain integration of polyzwitterionic groups. Furthermore, the load of risperidone (RISP) into gel matrix and release studies have been successively realized. The results indicated that the betainized novel gel is appropriate for using as a pH- and salt-controlled risperidone-releasing system. [ABSTRACT FROM AUTHOR]

In the current study, polylactide-co-glycolide (PLGA) nanoparticles entrapping both clozapine (CLZ) and risperidone (RIS) were formulated by spray-drying using Buchi Nano Spray Dryer B-90 (Flawil, Switzerland). Parameters such as inlet temperature, spray mesh diameter, sample flow rate, spray rate and applied pressure were optimized to produce nanoparticles having desired release profile using both low- and high-molecular weight PLGA polymer. Smallest size nanoparticle of size around 248 nm could be prepared using a 4.0 μm mesh diameter with low-molecular weight polymer. The load of CLZ and RIS was 126.3 and 58.2 μg/mg of polymer particles, respectively. Entrapment efficiency of drugs in PLGA nanoparticles was 94.74% for CLZ and 93.12% for RIS. Both the drugs released continuously from the nanoparticle formulations. PLGA nanoparticles formulated using low-molecular weight polymer released around 80% of the entrapped drug over 10 days of time. Nature of drug inside polymer particles was amorphous, and there was no chemical interaction of CLZ and RIS with polymer. Polymeric nanoparticles were found to be non-toxic in nature using PC12 cell line. This nanospray drying process proved to be suitable for developing polymeric nanoformulation delivering dual drugs for the treatment of Schizophrenia. [ABSTRACT FROM AUTHOR]

Risperidone is a poorly water soluble atypical antipsychotic drug. This work investigated the potential of developing risperidone effervescent tablets to facilitate drug administration and mask drug taste. The solid dispersion technique was selected to improve drug solubility due to its ease of scaling up, reproducibility and affordable cost. Thirty formulas were prepared adopting a 51.21.31full factorial design. Trehalose, Inulin, pregelatinized starch, carboxymethylcellulose sodium and Eudragit E100 were used as hydrophilic carriers at different ratios. Rotovap, lyophilization and the kneading-oven were applied as solvent evaporation techniques. Differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy showed that the drug was present as amorphous material entrapped within the carrier matrix. Eight tablet blends were prepared using different effervescent mixture ratios with or without binder and lubricant/glidant mixture. All of the blends had acceptable flowability, acceptable effervescence times and immediate drug release that could not be achieved by any of the control formulas. The formula of choice contained 40% effervescent mixture, 5% starch, 1% boric acid, 1% aspartame and sufficient lactose. The relative bioavailability (RB) of risperidone from this formula was 161.41% with a significantly higher extent of absorption compared to the market conventional tablets. This formula may be promising in improving patient compliance and drug efficiency. [ABSTRACT FROM AUTHOR]