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BMC Psychiatry

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Open Access 01-12-2018 | Research article

Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study

Authors: Daniel Schöttle, Wolfgang Janetzky, Daniel Luedecke, Elmar Beck, Christoph U. Correll, Klaus Wiedemann

Published in: BMC Psychiatry | Issue 1/2018

Abstract

Background

In this study, the treatment of schizophrenia patients with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic setting.

Methods

This multicenter, prospective, non-interventional study included 242 patients (age = 43.1 ± 15.1 years, 55.0% male) who were monitored during 6 months of AOM treatment. Endpoints included measurements of psychopathology (Brief Psychiatric Rating Scale, BPRS) and severity of illness scales (Clinical Global Impressions-Severity, CGI-S, and -Improvement, CGI-I). Furthermore, treatment-related adverse events (TRAEs) were recorded.

Results

At baseline, the mean BPRS total score was 54.1 ± 15.6, the mean CGI-S was 4.8 ± 0.8 and the most frequent illness category was ‘markedly ill’ (41.7%). Patients had been pretreated with oral aripiprazole for a mean duration of 9.7 months (SD: 22.3) and 87.9% were deemed by their clinician as “clinically stable” and for a mean of 5.9 months. The difference in global BPRS after 6 months was − 13.8 (SD: 16.0; 95% CI: [− 15.9; − 11.7]; p < 0.001). The proportion of patients with high CGI-S scores decreased and the proportion of patients with low scores increased significantly (p < 0.001, respectively). BPRS scores improved numerically especially well in younger patients ≤35 years, CGI-S scores decreased significantly more in this population. TRAEs were rare, with low incidences of extrapyramidal symptoms (2.9%) or weight increase (0.4%).

Conclusions

Treatment with AOM showed satisfying effectiveness in outpatients with further improvement of psychopathology after oral aripiprazole treatment for a considerable duration and even after having achieved clinically judged “stability”. Our findings indicate a robust therapeutic effect of AOM and substantiate previous results from randomized controlled trials under real-world routine conditions.

Mitsonis C, Voussoura E, Dimopoulos N, Psarra V, Kararizou E, Latzouraki E, et al. Factors associated with caregiver psychological distress in chronic schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 2012;47:331–7. https://doi.org/10.1007/s00127-010-0325-9.CrossRefPubMed

Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067. https://doi.org/10.1038/nrdp.2015.67.CrossRefPubMed

Lindenmayer J-P, Liu-Seifert H, Kulkarni PM, Kinon BJ, Stauffer V, Edwards SE, et al. Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response. J Clin Psychiatry. 2009;70:990–6. https://doi.org/10.4088/JCP.08m04221.CrossRefPubMed

Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013;12:216–26. https://doi.org/10.1002/wps.20060.CrossRefPubMedPubMedCentral

Szkultecka-Dębek M, Miernik K, Stelmachowski J, Jakovljević M, Jukić V, Aadamsoo K, et al. Schizophrenia causes significant burden to patients’ and caregivers’ lives. Psychiatr Danub. 2016;28:104–10.PubMed

Suzuki T, Uchida H, Takeuchi H, Tsuboi T, Hirano J, Mimura M. A review on schizophrenia and relapse--a quest for user-friendly psychopharmacotherapy. Hum Psychopharmacol. 2014;29:414–26. https://doi.org/10.1002/hup.2421.CrossRefPubMed

Perkins DO. Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry. 2002;63:1121–8.CrossRef

Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63:892–909.CrossRef

Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2014;16:505–24.PubMedPubMedCentral

10.

Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv. 2004;55:886–91. https://doi.org/10.1176/appi.ps.55.8.886.CrossRefPubMed

11.

De Hert M, Sermon J, Geerts P, Vansteelandt K, Peuskens J, Detraux J. The use of continuous treatment versus placebo or intermittent treatment strategies in stabilized patients with schizophrenia: a systematic review and meta-analysis of randomized controlled trials with first- and second-generation antipsychotics. CNS Drugs. 2015;29:637–58. https://doi.org/10.1007/s40263-015-0269-4.CrossRefPubMed

12.

Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013;74:957–65. https://doi.org/10.4088/JCP.13r08440.CrossRefPubMed

13.

Correll CU, Citrome L, Haddad PM, Lauriello J, Olfson M, Calloway SM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1–24. https://doi.org/10.4088/JCP.15032su1.CrossRefPubMed

14.

Kishimoto T, Hagi K, Nitta M, Leucht S, Olfson M, Kane JM, 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. 2017;44:603–19. https://doi.org/10.1093/schbul/sbx090.CrossRef

15.

Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002;302:381–9. https://doi.org/10.1124/jpet.102.033175.CrossRefPubMed

16.

Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu L-X, Sibley DR, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003;28:1400–11. https://doi.org/10.1038/sj.npp.1300203.CrossRefPubMed

17.

de Boer MK, Castelein S, Wiersma D, Schoevers RA, Knegtering H. The facts about sexual (Dys)function in schizophrenia: an overview of clinically relevant findings. Schizophr Bull. 2015;41:674–86. https://doi.org/10.1093/schbul/sbv001.CrossRefPubMedPubMedCentral

18.

Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA. The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol. 2002;441:137–40.CrossRef

19.

Stark AD, Jordan S, Allers KA, Bertekap RL, Chen R, Mistry Kannan T, et al. Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT 2A receptors: functional receptor-binding and in vivo electrophysiological studies. Psychopharmacology. 2007;190:373–82. https://doi.org/10.1007/s00213-006-0621-y.CrossRefPubMed

20.

Kane JM, Sanchez R, Perry PP, Jin N, Johnson BR, Forbes RA, et al. Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012;73:617–24. https://doi.org/10.4088/JCP.11m07530.CrossRefPubMed

21.

Fleischhacker WW, Sanchez R, Perry PP, Jin N, Peters-Strickland T, Johnson BR, et al. Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study. Br J Psychiatry. 2014;205:135–44. https://doi.org/10.1192/bjp.bp.113.134213.CrossRefPubMed

22.

Potkin SG, Preda A. Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia. Expert Opin Pharmacother. 2016;17:395–407. https://doi.org/10.1517/14656566.2015.1114100.CrossRefPubMed

23.

Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep. 1962;10:799–812.CrossRef

24.

Guy W. ECDEU assessment manual for psychopharmacology - revised (DHEW Publ no ADM 76–338). Rockville: U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976.

25.

Naber D, Hansen K, Forray C, Baker RA, Sapin C, Beillat M, et al. Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia. Schizophr Res. 2015;168:498–504. https://doi.org/10.1016/j.schres.2015.07.007.CrossRefPubMed

26.

McKeage K. Aripiprazole: a review of its use in the treatment of manic episodes in adolescents with bipolar I disorder. CNS Drugs. 2014;28:171–83. https://doi.org/10.1007/s40263-013-0134-2.CrossRefPubMed

27.

Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, et al. The safety and tolerability of aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a double-blind, placebo-controlled, randomized withdrawal study. J Affect Disord. 2018;241:425–32. https://doi.org/10.1016/j.jad.2018.06.043.CrossRefPubMed

28.

Yan T, Greene M, Chang E, Hartry A, Touya M, Broder MS. Medication adherence and discontinuation of aripiprazole once-monthly 400 mg (AOM 400) versus Oral antipsychotics in patients with schizophrenia or bipolar I disorder: a real-world study using US claims data. Adv Ther. 2018. https://doi.org/10.1007/s12325-018-0785-y.

29.

Emsley R, Chiliza B, Asmal L. The evidence for illness progression after relapse in schizophrenia. Schizophr Res. 2013;148:117–21. https://doi.org/10.1016/j.schres.2013.05.016.CrossRefPubMed

30.

Stahl SM. Long-acting injectable antipsychotics: shall the last be first? CNS Spectr. 2014;19:3–5. https://doi.org/10.1017/S1092852913001016.CrossRefPubMed

31.

Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168:603–9. https://doi.org/10.1176/appi.ajp.2011.10081224.CrossRefPubMed

32.

Ishigooka J, Nakamura J, Fujii Y, Iwata N, Kishimoto T, Iyo M, et al. Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole. Schizophr Res. 2015;161:421–8. https://doi.org/10.1016/j.schres.2014.12.013.CrossRefPubMed

33.

Correll CU, Kern Sliwa J, Najarian DM, Saklad SR. Practical considerations for managing breakthrough psychosis and symptomatic worsening in patients with schizophrenia on long-acting injectable antipsychotics. CNS Spectr. 2018. In press.

34.

Velligan DI, Sajatovic M, Hatch A, Kramata P, Docherty JP. Why do psychiatric patients stop antipsychotic medication? A systematic review of reasons for nonadherence to medication in patients with serious mental illness. Patient Prefer Adherence. 2017;11:449–68. https://doi.org/10.2147/PPA.S124658.CrossRefPubMedPubMedCentral

35.

Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry. 2009;70(Suppl 4):1–46 quiz 47.PubMed

36.

Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40:192–213. https://doi.org/10.1093/schbul/sbs150.CrossRefPubMed

37.

Kirson NY, Weiden PJ, Yermakov S, Huang W, Samuelson T, Offord SJ, et al. Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry. 2013;74:568–75. https://doi.org/10.4088/JCP.12r08167.CrossRefPubMed

38.

Kane JM, Kishimoto T, Correll CU. Assessing the comparative effectiveness of long-acting injectable vs. oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry. J Clin Epidemiol. 2013;66(8 Suppl):S37–41. https://doi.org/10.1016/j.jclinepi.2013.01.012.CrossRefPubMedPubMedCentral

39.

Schöttle D, Schimmelmann BG, Ruppelt F, Bussopulos A, Frieling M, Nika E, et al. Effectiveness of integrated care including therapeutic assertive community treatment in severe schizophrenia-spectrum and bipolar I disorders: four-year follow-up of the ACCESS II study. PLoS One. 2018;13:e0192929. https://doi.org/10.1371/journal.pone.0192929.CrossRefPubMedPubMedCentral

40.

Schöttle D, Schimmelmann BG, Karow A, Ruppelt F, Sauerbier A-L, Bussopulos A, et al. Effectiveness of integrated care including therapeutic assertive community treatment in severe schizophrenia spectrum and bipolar I disorders: the 24-month follow-up ACCESS II study. J Clin Psychiatry. 2014;75:1371–9. https://doi.org/10.4088/JCP.13m08817.CrossRefPubMed

41.

Fleischhacker WW, Baker RA, Eramo A, Sanchez R, Tsai L-F, Peters-Strickland T, et al. Effects of aripiprazole once-monthly on domains of personal and social performance: results from 2 multicenter, randomized, double-blind studies. Schizophr Res. 2014;159:415–20. https://doi.org/10.1016/j.schres.2014.09.019.CrossRefPubMed

42.

Schreiner A, Svensson A, Wapenaar R, Cherubin P, Princet P, Serazetdinova L, et al. Long-acting injectable risperidone and oral antipsychotics in patients with schizophrenia: results from a prospective, 1-year, non-interventional study (InORS). World J Biol Psychiatry. 2014;15:534–45. https://doi.org/10.3109/15622975.2014.902990.CrossRefPubMed

43.

Peters-Strickland T, Zhao C, Perry PP, Eramo A, Salzman PM, McQuade RD, et al. Effects of aripiprazole once-monthly on symptoms of schizophrenia in patients switched from oral antipsychotics. CNS Spectr. 2016;21:1–6. https://doi.org/10.1017/S1092852916000365.CrossRef

44.

Meduri M, Gregoraci G, Baglivo V, Balestrieri M, Isola M, Brambilla P. A meta-analysis of efficacy and safety of aripiprazole in adult and pediatric bipolar disorder in randomized controlled trials and observational studies. J Affect Disord. 2016;191:187–208. https://doi.org/10.1016/j.jad.2015.11.033.CrossRefPubMed

45.

Atar D, Ong S, Lansberg PJ. Expanding the evidence base: comparing randomized controlled trials and observational studies of statins. Am J Ther. 2015;22:e141–50. https://doi.org/10.1097/MJT.0b013e318245ce94.CrossRefPubMed

46.

Rouch L, Cestac P, Hanon O, Cool C, Helmer C, Bouhanick B, et al. Antihypertensive drugs, prevention of cognitive decline and dementia: a systematic review of observational studies, randomized controlled trials and meta-analyses, with discussion of potential mechanisms. CNS Drugs. 2015;29:113–30. https://doi.org/10.1007/s40263-015-0230-6.CrossRefPubMed

47.

Golder S, Loke YK, Bland M. Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: methodological overview. PLoS Med. 2011;8:e1001026. https://doi.org/10.1371/journal.pmed.1001026.CrossRefPubMedPubMedCentral

48.

Ahrén B, Mathieu C, Bader G, Schweizer A, Foley JE. Efficacy of vildagliptin versus sulfonylureas as add-on therapy to metformin: comparison of results from randomised controlled and observational studies. Diabetologia. 2014;57:1304–7. https://doi.org/10.1007/s00125-014-3222-z.CrossRefPubMed

49.

Naudet F, Maria AS, Falissard B. Antidepressant response in major depressive disorder: a meta-regression comparison of randomized controlled trials and observational studies. PLoS One. 2011;6:e20811. https://doi.org/10.1371/journal.pone.0020811.CrossRefPubMedPubMedCentral

50.

Conaty S, Watson L, Dinnes J, Waugh N. The effectiveness of pneumococcal polysaccharide vaccines in adults: a systematic review of observational studies and comparison with results from randomised controlled trials. Vaccine. 2004;22:3214–24. https://doi.org/10.1016/j.vaccine.2003.08.050.CrossRefPubMed

51.

Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med. 2000;342:1887–92. https://doi.org/10.1056/NEJM200006223422507.CrossRefPubMedPubMedCentral

52.

Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N Engl J Med. 2000;342:1878–86. https://doi.org/10.1056/NEJM200006223422506.CrossRefPubMed

53.

Yang W, Zilov A, Soewondo P, Bech OM, Sekkal F, Home PD. Observational studies: going beyond the boundaries of randomized controlled trials. Diabetes Res Clin Pract. 2010;88(Suppl 1):S3–9. https://doi.org/10.1016/S0168-8227(10)70002-4.CrossRefPubMed

Title: Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study
Authors: Daniel Schöttle
Wolfgang Janetzky
Daniel Luedecke
Elmar Beck
Christoph U. Correll
Klaus Wiedemann
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Psychiatry / Issue 1/2018
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/s12888-018-1946-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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