Oral Second-generation Antipsychotics Research Articles

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.

On- and off-label utilisation of antipsychotics in Australia (2000-2021): Retrospective analysis of two medication datasets.

To determine antipsychotic utilisation patterns in Australian adults from 2005 to 2021, with a focus on on-label and off-label prescriptions. We examined antipsychotic dispensing trends in adults from 2005 to 2021 using a 10% sample of the Pharmaceutical Benefits Scheme (PBS) dataset, which contains patient-level information on medicines dispensed throughout Australia. The lack of diagnostic information in PBS was substituted by analysing BEACH (Bettering the Evaluation And Care of Health) dataset, a cross-sectional national survey from 2000 to 2016, consisting of data from general practitioner-patient encounters. There were 5.6 million dispensings for 164,993 patients in PBS throughout this period; 69% patients had >1 dispensing, with a median of 6 per patient. Calculating the estimated period of exposure gave a total of 693,562 treatment episodes, with a median duration of 80 days. There were steady increases in both the incidence and prevalence of antipsychotic dispensings, mainly due to oral second-generation antipsychotics. The most commonly prescribed antipsychotics were quetiapine, olanzapine and risperidone, with a significant portion of patients receiving low-dose quetiapine without dose titration. Analysis of diagnostic indications from BEACH indicated that 27% of antipsychotic prescriptions were off-label for indications such as depression, dementia, anxiety and insomnia, at much lower prescribed daily dosages. The increasing prescribing and off-label use highlights concerns about chronic adverse effects caused by antipsychotics. The combined analysis of medication dispensings and the diagnostic indications for which they are prescribed is a novel approach and throws a spotlight on the need for additional monitoring of antipsychotics.

Frequency of sexual dysfunction in outpatients with severe mental illness in Greece.

Patients with psychosis can develop sexual dysfunction, which may be related to the disease itself, psychosocial factors, somatic comorbidities, and the use of psychotropic medication. We aimed to investigate the type and frequency of sexual dysfunction in patients diagnosed with schizophrenia or bipolar disorder in order to assess the side effects of antipsychotics in sexual function. This is a multicenter, cross-sectional study, involving patients diagnosed with schizophrenia (79.3%) or bipolar disorder (20.7%) treated in the Department of Psychiatry and Community Mental Health Centers from November 2018 to December 2019. Patients were enrolled in the study after signed informed consent. Demographic and clinical data were collected from patients through a semi-structured interview. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) was administered to assess sexual function. A total of 87 outpatients on antipsychotics were recruited in the study. The mean age was 43.6 years, while the mean duration of the disease was 16.9 years. Overall, only 9.1% of patients spontaneously reported sexual dysfunction. Patients treated with oral first-generation antipsychotics had more difficulties in achieving orgasm and decreased erection capacity. In contrast, patients treated with oral second-generation antipsychotics had decreased ejaculation capacity. Patients on antipsychotic combination therapy were associated with higher rates of sexual anhedonia. These results suggest that sexual dysfunction is a side effect of antipsychotic treatment, which was spontaneously rarely reported by patients. It seems essential to obtain a psychosexual clinical history before initiating antipsychotic treatment to evaluate following changes and adopt an individualized strategy to manage sexual dysfunction induced by antipsychotics.

Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.

Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1. Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations. SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.

Effectiveness of SGA-LAIs on Clinical, Cognitive, and Social Domains in Schizophrenia: Results from a Prospective Naturalistic Study

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

The relevance of long-acting injectables in the treatment of schizophrenia

Oral second-generation antipsychotics were introduced in the 1990s and long-acting injectables (LAIs; also known as depot) became available a decade later. LAIs used to be prescribed mainly to patients who did not adhere to treatment, and from personal clinical experience, patients still report today that they perceived it as a penalty to receive LAIs. After scarce prescribing until around 2010, the rate of LAIs being prescribed increased over the past decade, not only for schizophrenia but also off-label for bipolar disorder.

Reasons for Antipsychotic Treatment Switch

Objective: Switching of antipsychotic medications, which are used for many psychiatric conditions, is common. However, reasons and clinical documentation of such switches have scarcely been studied.Methods: A systematic, retrospective review of prescription records and prescriber notes was conducted to characterize reasons for and types of antipsychotic switches at one hospital during inpatient or outpatient care, starting August 1, 2017, until 270 antipsychotic switches with type and reasons were collected, as required by power analysis.Results: After removing 7 cases in which quetiapine was switched to a non-antipsychotic agent, 263 antipsychotic switches involving 195 unique subjects (median age = 31 [interquartile range, 24-47] years; schizophrenia = 36.9%, bipolar disorder = 27.7%, schizoaffective disorder = 18.5%) were analyzed. Frequent reasons for antipsychotic switch were intolerability (45.7%) and inefficacy/clinical worsening (17.6%). Reasons did not differ by race (P = .2644), age (P = .0621), or insurance type (P = .2970), but differed heterogeneously regarding different reasons by sex (P = .004). The most common reported switches were from second-generation oral antipsychotics (SGA-OAPs) to other SGA-OAPs (N = 155, 58.9%), mostly due to tolerability or inefficacy; second-generation long-acting injectable antipsychotics (SGA-LAIs) to SGA-OAPs (11%), mostly due to intolerability, patient preference, or insurance coverage problems; and SGA-OAPs to SGA-LAIs (10.7%) due to nonadherence. Reasons for antipsychotic switch were properly documented in 208 (79.1%) of the prescriber notes.Conclusions: In this retrospective chart review, switching varied by sex regarding reasons and occurred almost in half of the cases due to intolerability. Different reasons predominated in switches from SGA-OAP to SGA-OAP, SGA-LAI to SGA-OAP, and SGA-OAP to SGA-LAI. One in 5 switches were not properly documented, requiring attention.

Praktyka preskrypcyjna w zakresie leków przeciwpsychotycznych w schizofrenii w latach 2013–2018 na podstawie danych Narodowego Funduszu Zdrowia

The aim of the study was to analyse the prescribing pattern of antipsychotic drugs in patients with schizophrenia during the years 2013-2018. Schizophrenia is analysed as one of the diseases with the highest rate of Disability-Adjusted Life Years - DALY. In this study, the unitary data of the National Health Fund (NFZ) reported in the years 2013-2018 were used. Adult patients were identified by their Personal Identification Number (PESEL), and the antipsychotics were identified by the European Article Number (EAN). The study included 209,334 adults who were diagnosed with F20 to F20.9 (according to ICD-10) and were prescribed at least one antipsychotic within a year. The active substances of prescribed antipsychotic medication have been divided into typical (first generation), atypical (second generation) and long-acting injectable antipsychotics (both first and second generation). The statistical analysis contains descriptive statistics for selected sections. A linear regression, one-way analysis of variance and t-test were used in the study. All statistical analyses were performed using R, version 3.6.1 and Microsoft Excel. In the years 2013-2018, the number of patients in the public sector diagnosed with schizophrenia increased by 4%. The largest increase was recorded among persons diagnosed with other schizophrenia (F20.8). In the analysed years, the number of patients who were prescribed second-generation oral antipsychotics increased significantly as well as the number of patients who were prescribed long-acting antipsychotics, especially the secondgeneration agents (risperidone LAI, olanzapine LAI). The most prescribed first-generation antipsychotics included: perazine, levomepromazine and haloperidol with a downward trend for each; and the most common second-generation drugs included: olanzapine, aripiprazole and quetiapine. A noteworthy finding was an extremely high increase in the frequency of prescribing haloperidol in the form of depot. Extending the study to include information on applied prescriptive practice in the private sector would provide a fuller picture of the studied phenomenon.

Second-Generation Antipsychotics' Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders.

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics’ (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms.

Systematic Review of Real-World Treatment Patterns of Oral Antipsychotics and Associated Economic Burden in Patients with Schizophrenia in the United States.

BackgroundSchizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25–1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed.ObjectiveWe conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA.Data SourcesWe searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars.Study EligibilityObservational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included.ResultsEighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine.LimitationsThis systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system.ConclusionsIn the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02232-z.

Clinical Effectiveness of Second-Generation Injectable Antipsychotics


 The evidence in this report is limited because statistical information was not adequately reported in included studies.
 When comparing second-generation paliperidone palmitate injections and first-generation haloperidol decanoate injections, there is little-to-no difference in treatment success or adverse events.
 When comparing second-generation risperidone injections and first-generation haloperidol decanoate and fluphenazine decanoate injections given together, there is little-to-no difference in whether patients discontinue treatment.
 Hospitalization appears higher for patients who receive haloperidol decanoate injections compared to those who receive second-generation risperidone or aripiprazole injections, but there is little-to-no difference when comparing injections of risperidone to those of haloperidol decanoate and fluphenazine decanoate given together.
 There is little-to-no difference between patients who stop treatment when comparing risperidone injections to any oral second-generation antipsychotics, second-generation olanzapine injections compared to oral olanzapine, or aripiprazole injections compared to oral aripiprazole. There is little-to-no difference in adverse events between patients given aripiprazole injections compared to those given oral aripiprazole.
 Some studies showed a difference in relapse between second-generation injections compared to oral second-generation medication, while other studies showed little-to-no differences.
 Patients may experience fewer hospital days when given olanzapine injections compared to those receiving oral olanzapine.

Antipsychotic utilization trajectories three years after initiating or reinitiating treatment of schizophrenia: A state sequence analysis approach.

This study aims to describe the utilization patterns of antipsychotic (AP) medication in patients with schizophrenia (SCZ), three years after initiating or reinitiating a given AP. Based on medico-administrative information on patients living in Quebec (Canada), this retrospective cohort study included 6444 patients with a previous diagnosis of SCZ initiating or reinitiating AP medication between January 1, 2012, and December 31, 2014, with continuous coverage by public drug insurance. For each day of follow-up (1092days), patient was either exposed to one of the chosen categories of APs, or to none. This patient's sequence of AP exposure overtime has been referred to as the "antipsychotic utilization trajectory". These trajectories were analyzed using a State Sequence Analysis, an innovative approach which provides useful visual information on the continuation and discontinuation patterns of use over time. Clozapine and long-acting injectable second-generation APs had the best continuation and discontinuation patterns over 3years among all other groups, including less switching of APs, while oral first-generation APs had the poorest patterns. These findings were comparable among incident and non-incident cohorts. Oral second-generation antipsychotics, excluding clozapine, had a poorer continuation and discontinuation pattern than long-acting injectable antipsychotics. State Sequence Analysis provides a clear representation of treatment adherence in comparison with dichotomous indicators of adherence or discontinuation. Consequently, this innovative method has shed light on the impact of the AP chosen to initiate or reinitiate treatment in SCZ, which has been identified as a key factor for long-term treatment continuation and discontinuation.

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder

BackgroundMany second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk.MethodsPatients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013–February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions.ResultsMedian follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG.ConclusionsIn this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.

Persistence With and Adherence to Paliperidone Palmitate Once-Monthly Injection for Schizophrenia Treatment in China and Japan

Objective: To describe persistence with and adherence to paliperidone palmitate once-monthly injection (PP1M) compared to oral second-generation antipsychotics (SGAs) in patients with schizophrenia in real-world settings in China and Japan.Methods: Patients with a schizophrenia diagnosis (ICD-10: F20.x) who received oral or injectable antipsychotics from study start (China: January 1, 2012; Japan: January 1, 2014) until December 31, 2017, were enrolled in this retrospective cohort study. The first PP1M or oral SGA prescription date during the study period was defined as the index date. Eligible patients were followed up for up to 1 year after the index date. Persistence was measured from the index date until discontinuation or reaching 1 year. Adherence was assessed by calculating the proportion of days covered (PDC). Multivariable regression models were used to adjust for potential confounders.Results: The study cohorts comprised 44,266 patients from Japan and 7,564 and 5,189 patients, respectively, from 2 hospitals in China. The PP1M group showed consistently lower risk of discontinuation; adjusted hazard ratios and 95% CIs were 0.75 (0.72-0.90) (Japan), and 0.76 (0.68-0.84) and 0.65 (0.56-0.76) (China) compared to oral SGAs. The PP1M group also showed better adherence; adjusted odds ratios and 95% CIs were 1.61 (1.22-2.11) (Japan), and 1.92 (1.53-2.41) and 2.25 (1.58-3.23) (China).Conclusions: Persistence and adherence were significantly higher in PP1M users than in oral SGAs users across 3 databases comprising patients in 2 countries in Asia.

Antipsychotic utilisation and persistence in Australia: A nationwide 5-year study.

To evaluate the utilisation and persistence of antipsychotics for the treatment of schizophrenia in Australia. A retrospective study using the Australian Pharmaceutical Benefits Scheme database of a representative 10% sample. All adults with schizophrenia who were dispensed three or more supplies of oral (including clozapine) or long-acting injectable antipsychotics between 1 June 2015 and 31 May 2020 were included. Persistence time in treatment was evaluated using survival analysis and Cox hazard ratios. In all, 26,847 adults with schizophrenia were studied. Oral second-generation antipsychotics were more frequently dispensed than the other antipsychotic groups studied. Median treatment persistence times were 18.3 months for second-generation antipsychotic long-acting injectables, 10.7 months for oral second-generation antipsychotics and were significantly lower for both formulations of first-generation antipsychotics at 5.2 months (long-acting injectables) and 3.7 months (oral). The median persistence time for clozapine was significantly longer than all other antipsychotics groups. Oral second-generation antipsychotics and second-generation antipsychotic long-acting injectables accounted for over 75% and 13% of all antipsychotics in Australia, respectively. Concerns over medication adherence and subsequent relapse have not translated into increased long-acting injectable usage despite their significantly longer persistence. Clozapine, the single most 'persistent' antipsychotic, was only used in 9% of people, although up to a third of all cases are likely to be treatment-resistant. Our data suggest clinicians should give consideration to the earlier use of second-generation antipsychotic long-acting injectables and clozapine, to ameliorate prognosis in schizophrenia.

Self- and caregiver-perceived disability, subjective well-being, quality of life and psychopathology improvement in long-acting antipsychotic treatments: a 2-year follow-up study

Objective Switching to long-acting injectable (LAI) antipsychotic maintenance treatment (AMT) represents a valuable strategy for schizophrenia. In a recovery-oriented approach, patient-reported outcomes (PROs) such as perceived disability, subjective well-being, and quality of life cannot be neglected. Methods Forty clinically stable outpatients with schizophrenia treated with oral second-generation antipsychotics were enrolled at the time of switching to the equivalent dose of LAI. 35 subjects completed this 2-year longitudinal, prospective, open-label, observational study. Patients were assessed at baseline, after 1 year, and after 2 years of LAI-AMT, using psychometric scales (Positive And Negative Syndrome Scale, PANSS; Young Mania Rating Scale, YMRS; Montgomery-Åsberg Depression Rating Scale, MADRS), PROs (Subjective Well-Being under Neuroleptics short form, SWN-K; Short Form-36 health survey, SF-36; 12-item World Health Organisation Disability Assessment Schedule, WHODAS 2.0), and caregiver-reported outcomes (12-item WHODAS 2.0). Results No psychotic relapses were observed. Psychopathology measures (PANSS total and subscales – excluding negative symptoms), mood symptoms (YMRS, MADRS), perceived disability (patient- and caregiver-administered WHODAS 2.0), subjective well-being (SWN-K), and quality of life (SF-36) showed a concomitant amelioration after 1 year, without further significant variations. Discussion Switching to LAI-AMT may decrease perceived impairment, and increase subjective well-being and quality of life in clinically stable outpatients with schizophrenia. Highlights LAI treatment may improve outcomes by reducing psychopathology levels and relapses. In a recovery-oriented approach, patient-reported outcomes cannot be neglected. LAI antipsychotics may optimise the subjective experience of treatment. Switching to LAI therapy may result in a reduction in perceived disability. There is a significant correlation between proxy- and patient-reported disability.

Weight Gain and Treatment Interruptions with Second-Generation Oral Antipsychotics: Analysis of Patients with Schizophrenia or Bipolar I Disorder

Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.Funding. Alkermes, Inc.

Neuroleptic malignant syndrome associated with long-acting injectable versus oral second-generation antipsychotics: Analyses based on a spontaneous reporting system database in Japan

Long-acting injectable antipsychotics (LAI-APs) remain underutilized. One reason is the concern that LAI-APs might cause serious adverse events such as neuroleptic malignant syndrome (NMS) and lead to prolonged symptoms compared with oral treatment. Because the risk of NMS associated with LAI second-generation antipsychotics (LAI-SGAs) remains unclear, we compared reporting frequency, time to onset, and mortality of NMS between LAI- and oral SGAs using data from a Japanese spontaneous adverse event reporting database between April 2004 and September 2019. Of 5791 patients reporting adverse events due to LAI-SGAs or the equivalent oral SGAs, 768 (13%) developed NMS. LAI aripiprazole and LAI paliperidone were associated with a significantly lower reporting frequency of NMS than the equivalent oral SGAs (adjusted reporting odds ratio [95% confidence interval]: 0.35 [0.19–0.63] and 0.40 [0.27–0.59], respectively). Between 42% and 62% of the NMS associated with LAI- and oral SGAs other than LAI risperidone occurred within 30 days after initiation. The proportion of mortality due to NMS associated with oral aripiprazole was 13.1% and no deaths occurred in patients with NMS associated with LAI aripiprazole. The proportions of mortality due to NMS associated with oral risperidone/paliperidone, LAI risperidone, and LAI paliperidone were 8.8%, 4.2%, and 3.4%, respectively. Our findings showed that LAI-SGAs were not associated with a higher reporting frequency and mortality of NMS compared with oral SGAs, although clinicians need to closely monitor the occurrence of NMS not only during oral SGA treatment, but also, and in particular, in the early stage of LAI-SGA treatment.

Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review.

ObjectiveTreatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns.MethodsStructured, systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database identified primary research studies (published 2008–2018) describing real-world SGA use in adults with bipolar disorder/BD-I.ResultsAmong 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs.LimitationsDifferent definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived.ConclusionDespite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.

Combination of Clozapine With Long-Acting Injectable Antipsychotics in Treatment-Resistant Schizophrenia: Preliminary Evidence From Health Care Utilization Indices.

Clozapine is indicated for treatment-resistant schizophrenia (TRS), but only 30%-60% of patients will respond. There have been studies of clozapine augmentation with oral second-generation antipsychotics with mixed results, but no studies considering the combination with long-acting injectable antipsychotics (LAIAs). This study is the first to attempt to establish the benefits of the combination of clozapine and LAIAs in TRS using a variety of outcome measures of symptomatology and quality of life. A mirror-image study design was employed to review outcome measures 2 years pre and post combination of clozapine with a LAIA in a small sample of patients with chronic schizophrenia or schizoaffective disorders followed by the assertive community treatment service in the community. Outcome measures include demographic data, Brief Psychiatric Rating Scale, Clinical Global Impressions Scale-Improvement and Severity, 24-item Behavior and Symptom Identification Scale, World Health Organization Quality of Life Scale, Health of the Nation Outcome Scales, Threshold Assessment Grid, number of admissions, emergency department (ED) visits, and hospital bed days. Paired sample t tests showed a statistically significant reduction in average ED visits and hospital admissions in the 2 years post combination, with an average 1.8 fewer ED visits (95% CI, 0.58-3.02, P = .024) and a mean reduction of 0.85 hospital admissions (95% CI , 0.363-1.337, P = .008). The reduction in hospital bed days post combination was not statistically significant. Chart reviews found insufficient data for analysis of the remaining outcome measures. The combination of clozapine and a long-acting injectable antipsychotic appears to reduce health care utilization in terms of ED visits and number of hospital admissions. Larger prospective studies will be required to confirm the results.