Treatment Persistence Between Long-Acting Injectable Versus Orally Administered Aripiprazole Among Patients with Schizophrenia in a Real-World Clinical Setting in Japan

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Abstract

Introduction

Persistence with antipsychotic treatment is critical in managing patients with schizophrenia. To evaluate whether aripiprazole long-acting injection (aripiprazole once-monthly, AOM) can contribute to longer treatment persistence compared with daily orally administered aripiprazole (OA) in real-world clinical settings in Japan, treatment persistence in patients with schizophrenia was compared between patients treated with AOM and those with OA, using a claims database compiled by JMDC Inc., Tokyo, Japan.

Methods

Data of patients with schizophrenia who newly initiated AOM or OA treatment between May 2015 and November 2017 were analyzed. The Cox proportional hazard model was used to estimate the hazard ratio (HR) for treatment discontinuation of AOM vs. OA treatment, adjusted for age, sex, chlorpromazine-equivalent dose of antipsychotics, and the number of psychiatric hospitalizations.

Results

The analysis included 198 patients in the AOM group and 1240 patients in the OA group (mean age 38.4 ± 11.9 years and 39.3 ± 12.4 years, respectively). The AOM group was significantly less likely to discontinue treatment than the OA group (adjusted HR 0.54, 95% confidence interval [CI] 0.43–0.68). When using the tolerable patients extracted from the OA group (i.e., patients with at least two OA prescriptions; n = 983) vs. the whole AOM group, AOM users were again significantly less likely to discontinue treatment (adjusted HR 0.67, 95% CI 0.53–0.86).

Conclusion

AOM was associated with longer treatment persistence than OA in the antipsychotic treatment of patients with schizophrenia in real-world clinical settings in Japan, suggesting that the use of AOM may contribute to longer antipsychotic treatment.

Electronic supplementary material

The online version of this article (10.1007/s12325-020-01396-w) contains supplementary material, which is available to authorized users.

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Most cited references 27

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A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia.

Jari Tiihonen, Jari Haukka, Mark Z. Taylor … (2011)

Data on the effectiveness of antipsychotics in the early phase of schizophrenia are limited. The authors examined the risk of rehospitalization and drug discontinuation in a nationwide cohort of 2,588 consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finland. The authors linked national databases of hospitalization, mortality, and antipsychotic prescriptions and computed hazard ratios, adjusting for the effects of sociodemographic and clinical variables, the temporal sequence of the antipsychotics used, and the choice of the initial antipsychotic for each patient. Of 2,588 patients, 1,507 (58.2%) collected a prescription for an antipsychotic during the first 30 days after hospital discharge, and 1,182 (45.7%, 95% confidence interval [CI]=43.7-47.6) continued their initial treatment for 30 days or longer. In a pairwise comparison between depot injections and their equivalent oral formulations, the risk of rehospitalization for patients receiving depot medications was about one-third of that for patients receiving oral medications (adjusted hazard ratio=0.36, 95% CI=0.17-0.75). Compared with oral risperidone, clozapine (adjusted hazard ratio=0.48, 95% CI=0.31-0.76) and olanzapine (adjusted hazard ratio=0.54, 95% CI=0.40-0.73) were each associated with a significantly lower rehospitalization risk. Use of any antipsychotic compared with no antipsychotic was associated with lower mortality (adjusted hazard ratio=0.45, 95% CI=0.31-0.67). In Finland, only a minority of patients adhere to their initial antipsychotic during the first 60 days after discharge from their first hospitalization for schizophrenia. Use of depot antipsychotics was associated with a significantly lower risk of rehospitalization than use of oral formulations of the same compounds. Among oral antipsychotics, clozapine and olanzapine were associated with more favorable outcomes. Use of any antipsychotic was associated with lower mortality.

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The Use of Long-Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence.

Christoph U. Correll, Leslie Citrome, Peter M Haddad … (2016)

Long-acting injectable antipsychotics (LAIs) are among the most effective treatments in psychiatry, yet they remain underutilized in clinical practice. Although LAIs are typically used to maintain treatment adherence in patients with chronic schizophrenia, recent research has suggested that they may also provide an effective treatment strategy for patients with early-phase or first-episode disease. In October 2015, a group of 8 experts on the management of schizophrenia and LAIs met to evaluate the evidence surrounding the efficacy, safety, and cost-effectiveness of LAIs and to develop practical recommendations regarding the clinical use, education, and unmet needs related to LAIs. Participants were also asked to rate the importance of several patient characteristics when choosing an LAI versus an oral antipsychotic, from the perspectives of 4 different stakeholder groups: patients, health care professionals, families, and payers. The evidence review demonstrated that LAIs are superior to placebo for acute and maintenance treatment of schizophrenia and, in general, appear to be similar to one another in terms of schizophrenia relapse prevention. Study design impacts the demonstrated efficacy of LAIs versus oral antipsychotics, but recent database and randomized controlled studies favor the use of LAIs in early-phase schizophrenia patients. LAIs vary considerably in their propensity to cause certain adverse effects, including weight gain, metabolic effects, extrapyramidal symptoms, and prolactin elevation, and these differences can be used to help guide LAI selection. Some studies, but not all, have demonstrated significant reductions in health care utilization or overall costs with LAIs. The expert panel identified several barriers to LAI use in current practice, including clinician lack of knowledge, negative attitudes about LAIs, and resource and cost issues. The participants also identified a number of additional factors that should be considered when weighing the use of LAI therapy, including medication adherence, relapse risk and severity, cognitive impairment, ease of use, substance misuse, access and cost, stigma, social support, patient autonomy, control over medication dosing, fear of needles, and the potential for patient harm due to relapses and associated loss of functioning. This evidence review, discussion, and summary recommendations may help clinicians, patients, families, payers, and other stakeholders to better characterize the role of LAIs in the treatment of schizophrenia.

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Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.

Terence E. Ryan, Frank Yocca, Tetsuro Kikuchi … (2002)

Aripiprazole is the first next-generation atypical antipsychotic with a mechanism of action that differs from currently marketed typical and atypical antipsychotics. Aripiprazole displays properties of an agonist and antagonist in animal models of dopaminergic hypoactivity and hyperactivity, respectively. This study examined the interactions of aripiprazole with a single population of human D2 receptors to clarify further its pharmacologic properties. In membranes prepared from Chinese hamster ovary cells that express recombinant D2L receptors, aripiprazole bound with high affinity to both the G protein-coupled and uncoupled states of receptors. Aripiprazole potently activated D2 receptor-mediated inhibition of cAMP accumulation. Partial receptor inactivation using the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) significantly reduced the maximum effect of aripiprazole on inhibition of cAMP accumulation. This effect was seen with concentrations of EEDQ that did not alter the maximal inhibitory effect of dopamine. Consistent with the expected effects of a partial agonist, increasing concentrations of aripiprazole blocked the action of dopamine with maximal blockade equal to the agonist effect of aripiprazole alone. The efficacy of aripiprazole relative to that of dopamine varied from 25% in cells that lacked spare receptors for dopamine to 90% in cells with receptor reserve. These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer. The receptor activity profile may underlie the unique activity of aripiprazole in animals and its antipsychotic activity in humans.

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Author and article information

Contributors

Hiromi Sano: sanoh@otsuka.jp

Journal

Journal ID (nlm-ta): Adv Ther

Journal ID (iso-abbrev): Adv Ther

Title: Advances in Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 0741-238X

ISSN (Electronic): 1865-8652

Publication date (Electronic): 4 June 2020

Publication date PMC-release: 4 June 2020

Publication date (Print): 2020

Volume: 37

Issue: 7

Pages: 3324-3336

Affiliations

[1 ]GRID grid.256115.4, ISNI 0000 0004 1761 798X, Department of Psychiatry, , Fujita Health University, ; Aichi, Japan

[2 ]GRID grid.252311.6, ISNI 0000 0000 8895 8686, Department of Education, College of Education, Psychology and Human Studies, , Aoyama Gakuin University, ; Tokyo, Japan

[3 ]GRID grid.419953.3, Medical Affairs, , Otsuka Pharmaceutical Co., Ltd., ; Osaka, Japan

[4 ]GRID grid.419953.3, Medical Affairs, , Otsuka Pharmaceutical Co., Ltd., ; Tokyo, Japan

Article

Publisher ID: 1396

DOI: 10.1007/s12325-020-01396-w

PMC ID: 7314731

PubMed ID: 32500455

SO-VID: 31d012a9-f8d7-43b4-bd88-2b3c86f03e92

License:

Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 27 February 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100007132, Otsuka Pharmaceutical;

Custom metadata

Keywords: antipsychotic,aripiprazole once-monthly,continuation rate,japan,long-acting injectable,schizophrenia

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Keywords: antipsychotic, aripiprazole once-monthly, continuation rate, japan, long-acting injectable, schizophrenia

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Treatment Persistence Between Long-Acting Injectable Versus Orally Administered Aripiprazole Among Patients with Schizophrenia in a Real-World Clinical Setting in Japan

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Abstract

Introduction

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Results

Conclusion

Electronic supplementary material

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Most cited references 27

A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia.

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence.

Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.

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