Clinical Application of Aripiprazole Monohydrate Long-Acting Injectables for the Treatment of Bipolar Type I Disorder: A Consensus Panel Report.

BackgroundPatients 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.ObjectivesThe 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.MethodsThis 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.ResultsThe 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 (mean 45.1, 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).ConclusionThese findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-024-01391-x.

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.

Disease relapse, all-cause mortality, and adverse events associated with long-acting injectable antipsychotics versus oral antipsychotics in older people with schizophrenia in Hong Kong: a population-based within-subject analysis.

How Would You Like to Take Your Medicine 2 Times a Year? Paliperidone Palmitate Every 6 Months for the Maintenance Treatment of Schizophrenia

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.

Recommandations Formalisées d’Experts de l’AFPBN : prescription des neuroleptiques et antipsychotiques d’action prolongée

PMH1 Examining ALL-Cause Admission Counts after Initial Antipsychotics Administration during Hospitalization for Schizophrenia, Schizoaffective Disorder, or Bipolar Disorder

Prescription patterns in patients with schizophrenia who discontinued long-acting injectable antipsychotics: A chart-review.

Background and importanceTreatment with long acting injectable (LAI) antipsychotics has been shown to improve treatment adherence compared with oral antipsychotics, but it is still controversial if adherence is modified with...

Background: Bipolar disorder often begins in adolescence or early adulthood, characterized by recurrent manic episodes that can lead to neurodegenerative brain changes and functional decline. While several oral second-generation antipsychotics are Food and Drug Administration (FDA)-approved for mania, adherence to maintenance treatment is frequently poor due to factors such as anosognosia, cognitive dysfunction, impulsivity, side effects aversion, and substance use. Long-acting injectable (LAI) antipsychotics, approved for adults with bipolar mania or schizoaffective disorder (bipolar type), offer a potential solution for adolescents with similar conditions. This study reports on the efficacy of LAI antipsychotics in managing bipolar mania in adolescents, tracking outcomes over up to a year with baseline and follow-up Young Mania Rating Scale (YMRS) assessments. Methods: The study included 116 adolescents with a mean age of 16.17 years (66% male, 48% white, 23% black). Of these, 73% were diagnosed with bipolar mania and 22% with schizoaffective disorder, bipolar type. The mean illness duration was 1.9 years, with a baseline YMRS score of 33.8 and a body mass index (BMI) of 23.4 kg/m². LAI antipsychotics administered included aripiprazole, paliperidone, and risperidone, given at intervals of 1, 2, or 3 months. Results: YMRS scores showed substantial improvement, declining to 21.7 at 1 month, 12.3 at 2 months, 4.9 at 6 months, and 3.0 at 1 year. Common side effects were increased appetite and weight gain (mean BMI rose to 26.3 kg/m²). There were no dropouts, although 12% of participants switched formulations due to side effects. Notably, 86.2% of adolescents improved sufficiently to return to school or work. While 28.4% experienced depressive episodes, there were no suicide attempts or deaths during the 4- to 14-month follow-up. Discussion: This study demonstrates that LAI antipsychotics can effectively stabilize adolescents with bipolar mania or schizoaffective disorder, bipolar type, showing a marked decline in YMRS scores and high rates of remission and functional recovery. Despite the lack of FDA approval for LAI antipsychotics in those younger than 18, our results from off-label use suggest significant efficacy and tolerability. Further FDA clinical trials are needed to explore LAI antipsychotic formulations in adolescents to address the needs of this high-risk, nonadherent population.

Long-acting injectable (LAI) antipsychotics were developed as a way to decrease pill burden and simplify medication regimens by allowing less frequent administration to assist with medication adherence. The purpose of this study was to determine whether LAI antipsychotics prevent or delay hospital readmission in patients with a known history of medication non-adherence. The study is a retrospective evaluation of 240 men and women 18-65 years of age diagnosed with bipolar disorder, schizophrenia, or schizoaffective disorder discharged from an inpatient state hospital over a 2 year period of time on a LAI antipsychotic (fluphenazine LAI, haloperidol LAI, risperidone LAI or paliperidone LAI) or oral antipsychotic. Patients on LAIs were matched to patients on an equivalent oral dose, psychiatric diagnosis, number of prior hospital admissions, and length of stay. Those who received a LAI (N = 120) had a significantly longer survival time (mean 278.0 days) without readmission compared to those who did not (N = 120; mean 243.6 days). There was no statistically significant difference in the frequency of one-year readmission between those who did receive a LAI (43.1%) and those who did not (56.9%). Those who received a LAI with administration frequency of a month or longer had a significantly longer survival time without readmission (mean 307.9 days) when compared to those with a shorter administration frequency (mean 245.0 days). This study revealed the use of LAI antipsychotics in those with a history of medication non-adherence, particularly those with longer administration frequency, have potentially promising outcomes.

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.

Aripiprazole is a second-generation partial dopamine D₂ receptor agonist antipsychotic approved for the treatment of schizophrenia and maintenance treatment of bipolar I disorder. As the only partial dopamine D₂ receptor agonist available in both oral and long-acting injectable (LAI) formulations, it provides flexibility for tailoring treatment across different phases of the illness. Two LAI formulations of aripiprazole monohydrate are available: aripiprazole once-monthly 400 mg and aripiprazole 2-month ready-to-use 960 mg, offering options to accommodate patient needs and preferences and support adherence. The aripiprazole monohydrate LAIs are well-supported options for early intervention and maintenance treatment, with evidence demonstrating clinical effectiveness in reducing relapse and hospitalizations while supporting enhanced adherence. LAI antipsychotics, including aripiprazole monohydrate, offer practical benefits for patients with schizophrenia, particularly those at risk for nonadherence or recurrent episodes. However, these formulations are often underutilized due to lingering stigma and misperceptions, leading many clinicians to defer use of these agents until later in the treatment course. To support earlier and more informed use of aripiprazole monohydrate LAIs, a panel of psychiatric experts convened to review the latest evidence and share clinical strategies for integrating this agent into a comprehensive treatment plan. This Academic Highlights section presents the main points of their consensus recommendations, offering practical guidance for prescribers seeking to optimize outcomes in patients with schizophrenia.

This study examined the prevalence of Long Acting Injectable (LAI) antipsychotics prescription and explored the nature and scope of such prescriptions in the context of polypharmacy in three major psychiatric treatment facilities in Saskatchewan, Canada. A cross-sectional study approach was used to collect data on LAI antipsychotics prescription details and de-identified demographics on all patients on admission on a specified date at the three study sites. Despite the availability of second generation LAI antipsychotics, first generation LAI antipsychotics accounted for 83.3% of the prescriptions (N = 96). Risperdal Consta was the only second generation LAI antipsychotic medication prescribed out of the six LAI antipsychotics in use. The most commonly prescribed LAI antipsychotic was zuclopenthixol decanoate (44.1%, N = 53). Most of the LAI antipsychotics were prescribed within the recommended dosages. Biweekly administration was the most common interval for the prescription of LAI antipsychotics (75%, N = 90). Polypharmacy was present amongst all patients including those on LAI antipsychotics. Co-prescription of antiparkinsonian medication was associated with the prescription of LAI antipsychotics. Patients with the diagnosis of Schizophrenia had more prescriptions for Zuclopenthixol decanoate (44.4%) and Risperidone Consta (24.4%) than those with the diagnoses of bipolar disorder (23.3% and 14.7%, respectively). A longitudinal approach to examining the LAI antipsychotic prescription practice would help to determine if concomitant prescription of LAI antipsychotics is associated with decrease in oral antipsychotic load.

Long-acting injectable (LAI) antipsychotics improve patient outcomes and are recommended by treatment guidelines for patients with limited medication adherence in schizophrenia spectrum, bipolar, and other psychotic disorders. Reports of LAI antipsychotic use in these disorders and if use aligns with treatment guidelines are lacking. This study aimed to report patient characteristics associated with LAI antipsychotic use in these disorders. Retrospective observational study of patients ≥18-years-old with bipolar or psychotic disorders at a large, integrated, community-based health system. Patient demographic and clinical characteristics served as exposures for the main outcome of adjusted odds ratio (aOR) for LAI versus oral antipsychotic medication use from January 1, 2017 to December 31, 2023. There were N = 2685 LAI and N = 31 531 oral antipsychotic users. Being non-white (aOR = 1.3-2.0; P < .0001), non-female (aOR = 1.5; P < .0001), from a high deprivation neighborhood (NDI, aOR = 1.3; P < .0007), having a higher body mass index (BMI, aOR = 1.3-1.7; P < .0009), having a schizophrenia/schizoaffective (aOR = 5.8-6.8; P < .0001), psychotic (aOR = 1.6, P < .0001), or substance use disorder (aOR = 1.4; P < .0001), and outpatient psychiatry (aOR = 2.3-7.5; P < .0001) or inpatient hospitalization (aOR = 2.4; P < .0001) utilization in the prior year with higher odds and age ≥40 (aOR = 0.4-0.7; P < .0001) or bipolar disorder (aOR = 0.9; P < .05) were associated with lower odds of LAI use. Non-white, non-female, age 18-39, and high NDI patients had higher LAI use regardless of treatment adherence markers. Smoking and cardiometabolic markers were also associated with LAI use. Demographic and clinical factors are associated with increased LAI use irrespective of treatment adherence. Research on utilization variation informing equitable formulation use aligned with treatment guideline recommendations is warranted.