Background: Long-acting injectable antipsychotics (LAIs) may potentially benefit patients requiring psychiatric hospitalization during the early stages of schizophrenia. However, few studies have compared the long-term effectiveness between patients who switched to LAIs and those who remained on oral antipsychotics (OAPs).
Methods: Using the Taiwan National Health Insurance Research Database, we constructed a population-based cohort with 19,813 new OAP users with ICD-9-CM–defined schizophrenia who were hospitalized from 2002 to 2005. Within this cohort, 678 patients who switched to LAIs during their hospitalization were identified. The LAI group was matched to patients who remained on OAPs (n = 678). The LAI cohort was further subdivided for analysis into patients who switched to LAIs within 3 years of OAP initiation (“an early stage”) and those who switched after 3 years (“a late stage”). Conditional Cox regressions and conditional negative binomial regressions were used to estimate the risk of death and the number of hospital visits between the two groups.
Results: During the 13-year study period, 312 patients switched to LAIs within the first 3 years of OAP initiation. All- and natural-cause mortalities in these patients were significantly lower than in those who remained on OAPs. The hazard ratios (HRs) for all- and natural-cause mortalities were 0.49 (95% confidence interval [CI], 0.27–0.87) and 0.30 (95% CI, 0.15–0.60), respectively. No significant decrease associated with LAIs was observed in unnatural-cause mortality. Patients receiving LAIs had lower risks of rehospitalization (incidence rate ratio [IRR] = 0.56, 95% CI, 0.45–0.69), psychiatric hospitalization (IRR = 0.63, 95% CI, 0.50–0.81), and psychiatric emergency room visits (IRR = 0.58, 95% CI, 0.45–0.75) compared to patients who remained on OAPs. Use of LAIs in the late stage of treatment did not decrease the risk of relapse or mortality.
Conclusions: Switching to LAIs during the first 3 years of treatment improved antipsychotic adherence, decreased relapses, and reduced long-term mortality. Our results provide evidence to support the benefits of early LAI treatment in schizophrenia.
Continue Reading...
Members enjoy unlimited free PDF downloads as part of their subscription! Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.
Crump C, Winkleby MA, Sundquist K, et al. Comorbidities and mortality in persons with schizophrenia: a Swedish national cohort study. Am J Psychiatry. 2013;170(3):324–333. PubMedCrossRef
Tiihonen J, Wahlbeck K, Lönnqvist J, et al. Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ. 2006;333(7561):224. PubMedCrossRef
Tiihonen J, Mittendorfer-Rutz E, Majak M, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia. JAMA Psychiatry. 2017;74(7):686–693. PubMedCrossRef
Keating D, McWilliams S, Schneider I, et al. Pharmacological guidelines for schizophrenia: a systematic review and comparison of recommendations for the first episode. BMJ Open. 2017;7(1):e013881. PubMedCrossRef
Taipale H, Mittendorfer-Rutz E, Alexanderson K, et al. Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia. Schizophr Res. 2018;197:274–280. PubMedCrossRef
Parellada E, Bioque M. Barriers to the use of long-acting injectable antipsychotics in the management of schizophrenia. CNS Drugs. 2016;30(8):689–701. PubMedCrossRef
Sacchetti E, Grunze H, Leucht S, et al. Long-acting injection antipsychotic medications in the management of schizophrenia. Evidence-Based Psychiatr Care. 2015;1:27–36.
Horvitz‐Lennon M, Predmore Z, Orr P, et al. Simulated long‐term outcomes of early use of long‐acting injectable antipsychotics in early schizophrenia. Early Interv Psychiatry. 2019;13(6):1357–1365. PubMed
Parellada E, Velligan DI, Emsley R, et al. Long-acting injectable antipsychotics in first-episode schizophrenia. Schizophr Res Treatment. 2012;2012:318535. PubMedCrossRef
Emsley R, Medori R, Koen L, et al. Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. J Clin Psychopharmacol. 2008;28(2):210–213. PubMedCrossRef
Kane JM, Schooler NR, Marcy P, et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(12):1217–1224. PubMedCrossRef
Huang C-Y, Fang S-C, Shao YJ. Comparison of long-acting injectable antipsychotics with oral antipsychotics and suicide and all-cause mortality in patients with newly diagnosed schizophrenia. JAMA Netw Open. 2021;4(5):e218810–e218810. PubMedCrossRef
Harvey PD, Loewenstein DA, Czaja SJ. Hospitalization and psychosis: influences on the course of cognition and everyday functioning in people with schizophrenia. Neurobiol Dis. 2013;53:18–25. PubMedCrossRef
Suissa S, Moodie EE, Dell’Aniello S. Prevalent new-user cohort designs for comparative drug effect studies by time-conditional propensity scores. Pharmacoepidemiol Drug Saf. 2017;26(4):459–468. PubMedCrossRef
Wen CP, Tsai SP, Chung WS. A 10-year experience with universal health insurance in Taiwan: measuring changes in health and health disparity. Ann Intern Med. 2008;148(4):258–267. PubMedCrossRef
Lu T-H, Lee M-C, Chou M-C. Accuracy of cause-of-death coding in Taiwan: types of miscoding and effects on mortality statistics. Int J Epidemiol. 2000;29(2):336–343. PubMedCrossRef
Ritchie CW, Harrigan S, Mastwyk M, et al. Predictors of adherence to atypical antipsychotics (risperidone or olanzapine) in older patients with schizophrenia: an open study of 3(1/2) years duration. Int J Geriatr Psychiatry. 2010;25(4):411–418. PubMedCrossRef
World Health Organization. ATC/DDD Index. 2014.
Karson C, Duffy RA, Eramo A, et al. Long-term outcomes of antipsychotic treatment in patients with first-episode schizophrenia: a systematic review. Neuropsychiatr Dis Treat. 2016;12:57–67. PubMedCrossRef
Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry. 2004;161(4):692–699. PubMedCrossRef
Jespersen CG, Nørgaard M, Bjerklund Johansen TE, et al. The influence of cardiovascular morbidity on the prognosis in prostate cancer: experience from a 12-year nationwide Danish population-based cohort study. BMC Cancer. 2011;11(1):519. PubMedCrossRef
Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168(6):603–609. PubMedCrossRef
Taipale H, Mehtälä J, Tanskanen A, et al. Comparative effectiveness of antipsychotic drugs for rehospitalization in schizophrenia-a nationwide study with 20-year follow-up. Schizophr Bull. 2018;44(6):1381–1387. PubMedCrossRef
Birchwood M, Todd P, Jackson C. Early intervention in psychosis: the critical period hypothesis. Br J Psychiatry suppl. 1998;172(S33):53–59. PubMedCrossRef
Munday J, Greene M, Chang E, et al. Early initiation of long-acting injectable antipsychotic treatment is associated with lower hospitalization rates and healthcare costs in patients with schizophrenia: real-world evidence from US claims data. Curr Med Res Opin. 2019;35(7):1231–1239. PubMedCrossRef
Torniainen M, Mittendorfer-Rutz E, Tanskanen A, et al. Antipsychotic treatment and mortality in schizophrenia. Schizophr Bull. 2015;41(3):656–663. PubMedCrossRef
Kishimoto T, Hagi K, Nitta M, et al. Effectiveness of long-acting injectable vs oral antipsychotics in patients with schizophrenia: a meta-analysis of prospective and retrospective cohort studies. Schizophr Bull. 2018;44(3):603–619. PubMed
Leucht C, Heres S, Kane JM, et al. Oral versus depot antipsychotic drugs for schizophrenia: a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res. 2011;127(1-3):83–92. PubMedCrossRef
Anderson KK, Voineskos A, Mulsant BH, et al. The role of untreated psychosis in neurodegeneration: a review of hypothesized mechanisms of neurotoxicity in first-episode psychosis. Can J Psychiatry. 2014;59(10):513–517. PubMedCrossRef
Ortiz BB, Eden FDM, de Souza ASR, et al. New evidence in support of staging approaches in schizophrenia: differences in clinical profiles between first episode, early stage, and late stage. Compr Psychiatry. 2017;73:93–96. PubMedCrossRef
Lieberman JA. Neurobiology and the natural history of schizophrenia. J Clin Psychiatry. 2006;67(10):e14. PubMedCrossRef