Oral Antipsychotics Research Articles

Early use of long-acting injectable antipsychotics in bipolar disorder type I: An expert consensus.

Long-acting injectable antipsychotics (LAIs) are not routinely offered to patients living with bipolar disorder type I (BP-I), despite widespread evidence that supports their benefits over oral antipsychotics, particularly in early disease. A round-table meeting of psychiatrists convened to discuss barriers and opportunities and provide consensus recommendations around the early use of LAIs for BP-I. LAIs are rarely prescribed to treat BP-I unless a patient has severe symptoms, sub-optimal adherence to oral antipsychotics, or has experienced multiple relapses. Beyond country-specific accessibility issues (e.g., healthcare infrastructure and availability/approval status), primary barriers to the effective use of LAIs were identified as attitudinal and knowledge/experience-based. Direct discussions between healthcare providers and patients about treatment preferences may not occur due to a preconceived notion that patients prefer oral antipsychotics. Moreover, as LAIs have historically been limited to the treatment of schizophrenia and the most severe cases of BP-I, healthcare providers might be unaware of the benefits LAIs provide in the overall management of BP-I. Improved treatment adherence associated with LAIs compared to oral antipsychotics may support improved outcomes for patients (e.g., reduced relapse and hospitalization). Involvement of all stakeholders (healthcare providers, patients, and their supporters) participating in the patient journey is critical in early and shared decision-making processes. Clinical and database studies could potentially bridge knowledge gaps to facilitate acceptance of LAIs. This review discusses the benefits of LAIs in the management of BP-I and identifies barriers to use, while providing expert consensus recommendations for potential solutions to support informed treatment decision-making.

Depot Versus Oral Antipsychotics in Patients with Schizophrenia: Which is Better on Side Effects, Functional Improvement, and Life Satisfaction

Depot Versus Oral Antipsychotics in Patients with Schizophrenia: Which is Better on Side Effects, Functional Improvement, and Life Satisfaction

An economic model to understand the cost-effectiveness of olanzapine orally dispersible tablets (ODT) and olanzapine film coated tablets as a group compared with other oral atypical antipsychotics for treating schizophrenia in Morocco

BackgroundAntipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco.MethodsThe study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty.ResultsAccording to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings.ConclusionsThe model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations.

Preferences for attributes of oral antipsychotic treatments: results from a discrete-choice experiment in respondents with schizophrenia or bipolar I disorder

BackgroundAntipsychotic medications are effective treatments for schizophrenia (SZ) and bipolar I disorder (BD-I), but when presented with different treatment options, there are tradeoffs that individuals make between clinical improvement and adverse effects. As new options become available, understanding the attributes of antipsychotic medications that are valued and the tradeoffs that individuals consider when choosing among them is important.MethodsA discrete-choice experiment (DCE) was administered online to elicit preferences across 5 attributes of oral antipsychotics: treatment efficacy (i.e., improvement in symptom severity), weight gain over 6 months, sexual dysfunction, sedation, and akathisia. Eligible respondents were aged 18–64 years with a self-reported clinician diagnosis of SZ or BD-I.ResultsIn total, 144 respondents with SZ and 152 with BD-I completed the DCE. Of those with SZ, 50% identified themselves as female and 69.4% as White, with a mean (SD) age of 41.0 (10.1) years. Of those with BD-I, most identified themselves as female (69.7%) and as White (77.6%), with a mean (SD) age of 40.0 (10.7) years. In both cohorts, respondents preferred oral antipsychotics with better efficacy, less weight gain, no sexual dysfunction or akathisia, and lower risk of sedation. Treatment efficacy was the most important attribute, with a conditional relative importance (CRI) of 31.4% for respondents with SZ and 31.0% for those with BD-I. Weight gain (CRI = 21.3% and 23.1%, respectively) and sexual dysfunction (CRI = 23.4% and 19.2%, respectively) were adverse effects in this study that respondents most wanted to avoid. Respondents with SZ were willing to accept 9.8 lb of weight gain or > 25% risk of sedation for symptom improvement; those with BD-I were willing to accept 8.5 lb of weight gain or a > 25% risk of sedation.ConclusionsIn this DCE, treatment efficacy was the most important attribute of oral antipsychotic medications among respondents with SZ and BD-I. Weight gain and sexual dysfunction were the adverse effects respondents most wanted to avoid; however, both cohorts were willing to accept some weight gain or sedation to obtain better efficacy. These results highlight features that patients value in antipsychotic medications and how they balance benefits and risks when choosing among treatments.

Healthcare utilization and economics evaluation of paliperidone palmitate once-monthly in schizophrenia: a one-year, real-world, and retrospective mirror image study in China.

Investigation and analysis of the changes in healthcare resources and burden of schizophrenia in the real world before and after switching from oral antipsychotics (OAPs) to paliperidone palmitate once-monthly (PP1M) could provide evidence to clinicians and patients for choosing treatment modality and data support for health policy optimization. The first dosage of PP1M was set as mirror point, and patients with mirror point between January 2020 and June 2022 were recruited in the study. The differences in treatment patterns, healthcare resource utilization, and costs within one year before and after the mirror point were compared. A total of 72 patients transitioning from OAPs to PP1M (mean age, 35.33 years; 43.06% female) were included in the study. Of the 72 patients, the application of PP1M resulted in a significant reduction in the hospitalization times, emergency room visits, and direct medical costs (P < 0.001), while the pharmacy cost and total cost increased by 222.57% (P < 0.001) and 16.35% (P < 0.001), respectively; PP1M accounted for 88.48% of the pharmacy cost. For patients with ≥1 hospitalization during the OAPs phase (n = 25), the number of hospitalizations, hospitalization days and hospitalization expenses decreased by more than 90% (P < 0.001). Total one-year expenses decreased by 37.67% (P < 0.001), and pharmacy expenses increased by 185.21% (P < 0.001). For patients with no hospitalizations during the OAPs phase (n = 47), emergency and outpatient visits decreased by 70% (P < 0.001) and 30.27% (P < 0.05), respectively, while the total cost increased by 117.56% (P < 0.001), and the pharmacy cost increased by 260.15% (P < 0.001) after initiation of PP1M treatment. After the transition to PP1M, the number of hospitalizations and outpatient and emergency department visits reduced, and healthcare resources were conserved. Switching to PP1M may be more economically beneficial for patients with prior hospitalizations while on OAP regimens. The high price of PP1M might be an obstacle to its widespread use.

Disability and Adverse Effects of Oral Versus Long-Acting Injectable Antipsychotics in Schizophrenia-Spectrum and Bipolar Disorder: A Comparison Based on Data-Driven Taxonomy.

Patients undergoing antipsychotic treatment for psychiatric disorders may experience challenges in functioning, either stemming from the severity of the illness or from the tolerability issues of prescribed medications. The aims of this cross-sectional study are to investigate the impact of adverse effects of antipsychotic drugs on patients' daily life functioning, comparing oral and long-acting injectable (LAI) antipsychotics, and further dividing antipsychotics by receptor-binding profiles based on recently defined data-driven taxonomy. This study involved patients with schizophrenia and bipolar spectrum disorders taking oral or LAI antipsychotics. Disability and functioning levels were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the adverse effects of medications were evaluated using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and its subscales. The total sample consisted of 126 participants with a diagnosis of schizophrenia-spectrum or bipolar disorder, and included 54 males and 72 females ranging from 18 to 78 years of age (mean45.1, standard deviation 14); 78 patients were taking oral antipsychotics and 48 were taking LAI antipsychotics, with subcategories of muscarinic (31), adrenergic/low dopamine (25), serotonergic/dopaminergic (23), dopaminergic (1), LAI muscarinic (15), LAI adrenergic (6), and LAI serotonergic/dopaminergic (25). The UKU total score for adverse effects showed significant correlations with WHODAS total score (ρ=0.475; p<0.001). Compared with oral antipsychotics, LAIs showed significantly lower scores in psychological (p=0.014), autonomic (p=0.008), other (p=0.004), and sexual adverse effects (p=0.008), as well as the UKU total score (p=0.002). The Kruskal-Wallis test showed a significant difference in adverse effects between LAI and oral muscarinic subgroups, with LAIs having lower scores compared with antipsychotics binding to muscarinic receptors (p=0.043). These findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies.

All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis.

Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66-0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66-0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63-0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59-1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66-0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

Efficacy and acceptability of long-acting antipsychotics in acutely ill individuals with schizophrenia-spectrum disorders: A systematic review and network meta-analysis

To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint.Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation.SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.

Real-World Adherence and Discontinuation of Oral Antipsychotics and Associated Factors in a National Sample of US Medicare Beneficiaries with Schizophrenia.

Little is known about adherence to and discontinuation of newly initiated oral antipsychotics (OAPs) as well as associated factors among Medicare beneficiaries with schizophrenia. This study aimed to examine rates of OAP adherence and discontinuation and associated factors in a national sample of fee-for-service Medicare beneficiaries with schizophrenia. This retrospective study used 100% fee-for-service Medicare claims data to identify adult beneficiaries with schizophrenia, initiating a new OAP between 01/01/2017 and 12/31/2019 (index date = date of new OAP prescription). Outcomes included adherence and discontinuation. Factors associated with adherence were assessed using logistic and linear regressions; Cox regressions were used to assess factors associated with discontinuation. In our final sample of 46,452 Medicare beneficiaries with schizophrenia, 35.4% were adherent to their newly initiated OAP (mean [SD] PDC: 0.52 [0.37]) over 12 months after initiation. Most patients (79.4%) discontinued their new OAP (median [IQR] time to discontinuation: 3.6 (1.0, 9.9) months). Factors associated with lower odds of adherence included younger age (OR: 0.43; 95% CI: 0.40-0.47, p <0.001 for patients aged 18-35 relative to patients aged ≥65 years); non-White race (OR: 0.72; 95% CI: 0.69-0.75, p <0.001 relative to White patients); and evidence of prior schizophrenia-related hospitalization (OR: 0.80; 95% CI: 0.77-0.83, p <0.001 relative to patients without evidence of prior schizophrenia-related hospitalization). Similar associations were observed for discontinuation outcomes. Twice-daily dosing frequency was also associated with lower odds of adherence (odds ratio [OR]: 0.93; 95% CI: 0.89-0.97, p = 0.0014) and higher hazard of discontinuation (hazard ratio [HR]: 1.03; 95% CI: 1.00-1.05, p = 0.0244) relative to once-daily dosing frequency. We found high rates of non-adherence and discontinuation among Medicare beneficiaries initiated on currently available OAPs. We also identified risk factors that contribute to increased odds of medication non-adherence. By identifying at-risk patient populations, targeted interventions can be initiated to facilitate treatment continuity.

Costs and affordability of psychotropic medicines for patients with schizophrenia in Nigeria

Background: Schizophrenia is a complex illness, in other words, requires certain costs to tackle the challenge. However, the use of psychotropic medicines is paramount for the disease management and the costs of these medications should be considered in the management especially in low- and – middle income countries. There is over-reliance on out-of-pocket payments among the individuals in these countries whereby a large number of the patients purchase the medicines out of pocket, and majority unable to afford the medicines for their illness. Aim: The aim of this study was to assess the costs and affordability of psychotropic medicines for management of Schizophrenia. It specifically evaluated the financial burden of out-of-pocket payment to purchase medicines for patients with Schizophrenia in Nigeria. Method: The study was conducted in a Neuropsychiatric Hospital in Southeastern part of Nigeria using a retrospective, cross-sectional study of the costs of psychotropic medicines for adult patients with Schizophrenia that visited the hospital. Results: All the prescribed oral typical antipsychotics (except chlorpromazine 200mg/day and 300mg/day) gave the patients less than one day wage to pay for medicines, whereas, all the oral atypical antipsychotics gave the patients more than one day wage to pay for the psychotropic medicines. Conclusion: The atypical antipsychotics were unaffordable to the patients. We considered various factors as limitation and recommend interventions for reimbursements or make the psychotropic medicines free for the patients.

Up-front matching: an ongoing recruitment method for prospective observational studies that mimics randomization for selected baseline covariates

ABSTRACT In a prospective observational study (POS) designed to assess the average causal effect of a treatment (e.g. Drug A) compared to a comparator (e.g. Drug B) in the treatment population, enrolling all patients who are assigned to the treatments of interest for follow-up has a potentially large negative impact on the statistical efficiency and bias of the analysis of the outcomes and on the cost of the study. “Up-front matching” is an innovative enrollment method for selecting patients for long-term follow-up among those who have already been assigned to treatment or comparator which uses frequency matching and hence avoids the restrictions of individual matching that other methods have used. To achieve potential statistical and logistical efficiencies in the POS, in up-front matching, a target population is defined based on a retrospective database which then enables selecting populations of patients for follow-up that have desirable statistical properties. In particular, the resulting populations of patients who are enrolled look like the population of treatment patients were randomized to treatment or comparator for the baseline covariates that are used to select patients for follow-up. The method is illustrated in detail for a study designed to assess the effect of injectable antipsychotics versus oral antipsychotics.

Long-Acting Injectable Antipsychotics in the Geriatric Population: A longitudinal Study

ObjectiveThis study compares demographic, clinical characteristics, and outcomes in older adults on long-acting injectable antipsychotics (LAI-AP) vs. oral antipsychotics (PO-AP). DesignThis observational study with a retrospective cohort utilized the electronic medical record's search engine to review charts of geriatric patients on LAI-AP for a two-year period. A convenience sample on PO-AP formed the comparison group. LAI-AP patients were subcategorized into discontinuation and continuation groups. SettingConducted at an urban, psychiatric outpatient clinic, using charts from October 2020 to 2022. ParticipantsPatients at least 60 years-old with psychotic or mood disorders on antipsychotics for at least 3-months during the study period. MeasurementsDemographic and clinical variables, including diagnosis, medication type, side effects, medical comorbidities, neurocognitive status, and secondary medications, were collected for both PO-AP and LAI-AP groups. Outcome variables included missed appointments, psychiatric and medical hospitalizations, and emergency room visits. Correlates of discontinuation of LAI-AP were also assessed. ResultsLAI-AP had a higher proportion than PO-AP of primary psychotic disorders (87.8% vs. 64.3%). During the study, PO-AP had higher rates of missed appointments (median 18% vs. 13% for LAI-AP) and psychiatric admissions (mean 0.019/month vs. 0.006/month for LAI-AP;); Female sex was a risk factor for discontinuation of LAI-AP (86.7% of discontinuation group vs. 55.2% of continuation group). ConclusionsThe LAI-AP group showed reduced hospitalizations, better treatment engagement, and comparable tolerability to PO-AP. Preliminary data suggests gender may influence LAI-AP discontinuation rates. This study adds to the sparse literature investigating the efficacy and tolerability of LAI-AP in geriatric patients.

Predictors of Readmission in Young Adults with First-Episode Psychosis: A Multicentric Retrospective Study with a 12-Month Follow-Up.

A significant number of young individuals are readmitted one or more times shortly after their first episode of psychosis. Readmission may represent a marker of psychopathological vulnerability. Our primary aim was to evaluate the impact of clinical and socio-demographic variables on readmission at 12-month follow-up. Secondly, our goal was to determine whether the use of Long-Acting Injection (LAI) antipsychotics provides notable benefits compared to oral medications in preventing subsequent readmissions. 80 patients hospitalised for the first time with a diagnosis of psychotic disorder (ICD-10 criteria) were retrospectively assessed through clinical records. The mean age was 21.7 years. Patients were predominantly male (n = 62, 77.5%), and 55 subjects had at least 8 years of education. 50% of the sample was "NEET" (not in education, employment, or training). 35 patients (43.8%) were discharged with a LAI antipsychotic, while 45 (56.2%) recieved oral antipsychotic therapy. Substance use (p = 0.04) and oral antipsychotics at discharge (p = 0.003) were significantly associated with readmission at 1 year. We did not find any significant predictors of being discharged with LAI therapy. Our findings underlined the importance of identifying patients at risk of readmission in order to prevent future rehospitalization and promote appropriate prevention strategies. LAIs should be considered as a first-choice treatment for patients hospitalised for FEP since they proved to be effective in preventing relapse.

In-Hospital Use of Long-Acting Injectable Antipsychotics and Readmission Risk in Patients With First-Admission Schizophrenia in Taiwan

Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge. To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs. This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022. In-hospital use of LAIs with or without early discontinuation. Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model. Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model. The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.

Neutrophil-Lymphocyte Ratio Values in Schizophrenia: A Comparison between Oral and Long-Acting Antipsychotic Therapies.

Schizophrenia is a mental disorder affecting approximately 0.32% of the global population, according to the World Health Organization. Antipsychotic medications are used to treat this condition by inhibiting D2 dopamine and 5HT2 serotonin receptors. The selection of the appropriate mode of delivery for these drugs is based on factors such as patient adherence, clinical presentation, and patient preferences. However, additional drivers of treatment selection are required in clinical practice. Mounting evidence suggests that neuroinflammation plays a crucial role in the pathogenesis of schizophrenia. NLR, a cost-effective biomarker of inflammation, has increased in several psychiatric conditions and may represent a valid method for studying the inflammatory stage in schizophrenia, relapse, and the first episode of psychosis. The aim of this study is to evaluate whether there are any variations in NLR values between patients given oral antipsychotics and those given long-acting antipsychotics. The study included 50 individuals with schizophrenia, either acute or in the follow-up phase. NLR was obtained by calculating the ratio of absolute neutrophil count (cells/μL) and absolute lymphocyte count (cells/μL). Patients on long-acting antipsychotics exhibited significantly lower mean NLR scores (1.5 ± 0.7) compared to those on oral antipsychotics (2.2 ± 1.3) (p < 0.05). NLR appears promising as a neuroinflammatory biomarker. This study reveals significantly lower NLR values in patients on long-acting antipsychotics, which may signify reduced systemic inflammation and improved adherence.

Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.

Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.

Clinical considerations and pitfalls in the use of depot antipsychotics

Long-acting injectable antipsychotics (LAI) is a frequently used treatment modality which has advantages over oral antipsychotics regarding hospitalization or relapse prevention. However, the pharmacokinetic properties of LAI greatly differ from oral antipsychotics. This necessitates an increased knowledge about LAI among clinicians, especially when commencing treatment, changing doses and discontinuing treatment. In this review, we summarize an array of clinically important characteristics of LAI and give a conceptual framework for understanding the pharmacokinetics of LAI.

Comparative Effectiveness of Long-Acting Injectable Versus Oral Antipsychotics in Patients With Schizophrenia Using the Prevalent New User Design and Subgroup Analyses.

We compared the effectiveness of long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in treating schizophrenia, focusing on whether the benefits of LAIs over OAs are evident even in the prevalent new user design and on effect heterogeneity. We conducted a prevalent new user cohort study using 2 administrative claims databases in Japan. We included patients with schizophrenia initiated on LAIs and propensity score-matched patients on OA. We compared the risks of psychiatric hospitalization and treatment discontinuation based on hazard ratios (HRs) using the Cox proportional hazards model. Effect heterogeneity was evaluated using subgroup analyses. In total, 2520 patients using LAI and OA were identified as matched cohorts. Long-acting injectable antipsychotics were associated with a higher psychiatric hospitalization risk than OAs (HR, 1.41; 95% confidence interval [CI], 1.06-1.88) in the entire population; however, LAIs were associated with lower risk in the group with a low proportion of days covered and psychiatric hospitalization history (HR, 0.51; 95% CI, 0.30-0.89). Long-acting injectable antipsychotics were associated with a lower risk of treatment discontinuation than OAs (HR, 0.76; 95% CI, 0.66-0.87) in the entire population; in the subgroup analyses, a consistent trend was observed in all strata (LAIs had a lower risk). Using a prevalent new user design, this study confirmed that LAIs have an advantage regarding treatment continuity. Long-acting injectable antipsychotics had higher psychiatric hospitalization risk than OAs in the entire population; however, this study suggested the presence of effect heterogeneity due to psychiatric hospitalization history.

Risk of Cardiovascular Events in Schizophrenic Patients Treated with Paliperidone Palmitate Once-Monthly Injection (PP1M): A Population-Based Retrospective Cohort Study in Taiwan.

Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia. This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs). Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression. Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N=10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively. This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs.

Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study

Objective Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. Methods The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. Results Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. Conclusions In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.