Long-Acting Injectable (LAI) Aripiprazole Formulations in the Treatment of Schizophrenia and Bipolar Disorder: a Systematic Review
- 139 Downloads
Several second-generation antipsychotics (SGAs) are available in long-acting injectable (LAI) formulations.
To systematically review the effects of the two formulations, Monohydrate and Lauroxil, of Aripiprazole LAI in patients with schizophrenia and bipolar disorder during an acute episode or during maintenance treatment.
On September 18, 2018, we adopted the following search strategy: (aripiprazole OR OPC-14597 OR Abilify) AND (long-acting OR depot OR LAI OR once monthly OR prolonged release OR monohydrate OR lauroxil) on PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials. Furthermore, we searched the ClinicalTrials.gov site for possible additional studies.
We included 28 papers dealing with randomised assignment of aripiprazole LAI formulations in schizophrenia and bipolar disorder in survival studies after stabilisation, in acute studies, and in head-to-head comparisons. Both monohydrate and lauroxil formulations reduced relapses/recurrences with respect to comparators (placebo or 50 mg once-monthly monohydrate) and improved symptomatology in acute schizophrenia.
Only a small number of studies were included in our review, with widely overlapping samples. While a high proportion of studies were wholly or partly industry-sponsored, their outcomes do not appear to have been affected.
Aripiprazole LAI may to be efficacious in reducing relapse of schizophrenia and bipolar disorder in the long term in stabilised patients and in improving symptoms of schizophrenia during its acute phase, with both monohydrate and lauroxil formulations showing efficacy.
We gratefully acknowledge the contribution of the Librarians of the School of Medicine and Psychology of Sapienza University, Ms. Mimma Ariano, Ms. Felicia Proietti, Ms. Ales Casciaro, Ms. Teresa Prioreschi, and Ms. Susanna Rospo for rendering precious bibliographical material accessible, as well as our Secretary Lucilla Martinelli for her assistance during the writing of this manuscript.
Compliance with Ethical Standards
This work has not been supported by any funding.
Conflict of interest
Drs. Girardi and Brugnoli received research grants from Otsuka during 2016–2017; Dr. Girardi received educational and research funds from Janssen, Lilly, Angelini, and Springer. All other authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in, or financial conflict with the subject matter or materials discussed in the manuscript.
- 2.Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry. 2006;67(Suppl 5):3–8.Google Scholar
- 4.Amano T, Matsubayashi H, Momiyama T, Ishihara K, Todo N, Sasa M. Antagonizing effects of a novel antipsychotic quinolinone derivative (OPC-14597) on dopaminergic inhibition of neuronal activities in the nucleus accumbens. Prog Neuropsychopharmacol Biol Psychiatry. 1995;19(1):105–16.CrossRefGoogle Scholar
- 6.Cañive JM, Lewine JD, Edgar JC, Davis JT, Miller GA, Torres F, Tuason VB. Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole. Psychopharmacol Bull. 1998;34(1):101–5.Google Scholar
- 7.United States Food and Drug Administration. Approval package for 21-436/S-005 & S-008 & 21-713/S-003. Rockville (Maryland): U.S. Food and Drug Administration; 2005.Google Scholar
- 8.European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP): Assessment report EMA/557557/2014. Procedure No. EMEA/H/C/000471/II/0101. London: EMA, 24 July 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000471/WC500174667.pdf. Accessed 11 Sept 2018.
- 11.Nahata T, Saini TR. Formulation optimization of long-acting depot injection of aripiprazole by using D-optimal mixture design. PDA J Pharm Sci Technol. 2009;63(2):113–22.Google Scholar
- 12.Kane JM, Sanchez R, Perry PP, Jin N, Johnson BR, Forbes RA, McQuade RD, Carson WH, Fleischhacker WW. 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(5):617–24.CrossRefGoogle Scholar
- 13.United States Food and Drug Administration (US FDA). Abilify Maintena™ (aripiprazole) for extended release injectable suspension, for intramuscular use: prescribing information. Revised on February 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202971s000lbl.pdf. Accessed 11 Sept 2018.
- 17.United States Food and Drug Administration (US FDA). Abilify Lauroxil (aripiprazole) for extended release injectable suspension, for intramuscular use: prescribing information. 10-02-2015. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=207533. Accessed 11 Sept 2018.
- 19.Turncliff R, Hard M, Du Y, Risinger R, Ehrich EW. Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia. Schizophr Res. 2014;159(2–3):404–10.CrossRefGoogle Scholar
- 22.Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.Google Scholar
- 23.Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, Moher D, Tugwell P, Welch V, Kristjansson E, Henry DA. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008.CrossRefGoogle Scholar
- 24.Miller SA. PICO Worksheet and Search Strategy. Los Angeles (CA): National Center for Dental Hygiene Research, University of Southern California; 2001.Google Scholar
- 25.Cohen J. Statistical power analysis for the behavioral sciences. New York: Routledge; 1988.Google Scholar
- 28.Higgins, J.P.T., Green, S. (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. London, UK: The Cochrane Collaboration, 2011. http://www.handbook.cochrane.org. Accessed 11 Sept 2018.
- 31.Kane JM, Sanchez R, Baker RA, Eramo A, Peters-Strickland T, Perry PP, Johnson BR, Tsai LF, Carson WH, McQuade RD, Fleischhacker WW. Patient-centered outcomes with aripiprazole once-monthly for maintenance treatment in patients with schizophrenia: results from two multicenter, randomized, double-blind studies. Clin Schizophr Relat Psychoses. 2015;9(2):79–87.CrossRefGoogle Scholar
- 34.Fleischhacker WW, Sanchez R, Perry PP, Jin N, Peters-Strickland T, Johnson BR, Baker RA, Eramo A, McQuade RD, Carson WH, Walling D, Kane JM. Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study. Br J Psychiatry. 2014;205(2):135–44.CrossRefGoogle Scholar
- 35.Ishigooka J, Nakamura J, Fujii Y, Iwata N, Kishimoto T, Iyo M, Uchimura N, Nishimura R, Shimizu N; ALPHA Study Group. 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(2–3):421–8.Google Scholar
- 36.Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, Perry P, Hertel P, Such P, Salzman PM, McQuade RD, Nyilas M, Carson WH. Efficacy and safety of aripiprazole once-monthly in the maintenance treatment of bipolar I disorder: a double-blind, placebo-controlled, 52-week randomized withdrawal study. J Clin Psychiatry. 2017;78(3):324–31.CrossRefGoogle Scholar
- 37.Fleischhacker WW, Sanchez R, Johnson B, Jin N, Forbes RA, McQuade R, Baker RA, Carson W, Kane JM. Long-term safety and tolerability of aripiprazole once-monthly in maintenance treatment of patients with schizophrenia. Int Clin Psychopharmacol. 2013;28(4):171–6.Google Scholar
- 38.Fleischhacker WW, Baker RA, Eramo A, Sanchez R, Tsai LF, Peters-Strickland T, Perry PP, McQuade RD, Johnson BR, Carson WH, Kane JM. Effects of aripiprazole once-monthly on domains of personal and social performance: results from 2 multicenter, randomized, double-blind studies. Schizophr Res. 2014;159(2–3):415–20.CrossRefGoogle Scholar
- 39.Kane JM, Peters-Strickland T, Baker RA, Hertel P, Eramo A, Jin N, Perry PP, Gara M, McQuade RD, Carson WH, Sanchez R. Aripiprazole once-monthly in the acute treatment of schizophrenia: findings from a 12-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75(11):1254–60.CrossRefGoogle Scholar
- 41.Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, Perry PP, Hertel P, Such P, McQuade RD, Nyilas M, Carson WH. 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.CrossRefGoogle Scholar
- 43.Ismail Z, Peters-Strickland T, Miguelez M, Baker RA, Hertel P, Eramo A, Jin N, Perry P, Sanchez R, McQuade RD, Kane JM. Aripiprazole once-monthly in the treatment of acute psychotic episodes in schizophrenia: post hoc analysis of positive and negative syndrome scale Marder factor scores. J Clin Psychopharmacol. 2017;37(3):347–50.CrossRefGoogle Scholar
- 44.Nasrallah HA, Newcomer JW, Risinger R, Du Y, Zummo J, Bose A, Stankovic S, Silverman BL, Ehrich EW. Effect of aripiprazole lauroxil on metabolic and endocrine profiles and related safety considerations among patients with acute schizophrenia. J Clin Psychiatry. 2016;77(11):1519–25.CrossRefGoogle Scholar
- 50.Naber D, Hansen K, Forray C, Baker RA, Sapin C, Beillat M, Peters-Strickland T, Nylander AG, Hertel P, Andersen HS, Eramo A, Loze JY, Potkin SG. Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia. Schizophr Res. 2015;168(1–2):498–504.CrossRefGoogle Scholar
- 51.Cuomo I, Kotzalidis GD, de Persis S, Piacentino D, Perrini F, Amici E, De Filippis S. Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI) versus paliperidone LAI in comorbid psychosis and substance use disorder: impact on clinical status, substance craving, and quality of life. Neuropsychiatr Dis Treat. 2018;14:1645–56.CrossRefGoogle Scholar
- 52.Girardi P, Del Casale A, Rapinesi C, Kotzalidis GD, Splendori F, Verzura C, Trovini G, Sorice S, Carrus D, Mancinelli I, Comparelli A, De Filippis S, Francomano A, Ballerini A, Marcellusi A, Mennini FS, Ducci G, Sani G, Pompili M, Brugnoli R. Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate. Hum Psychopharmacol. 2018;33(3):e2658.CrossRefGoogle Scholar
- 54.Potkin SG, Loze JY, Forray C, Baker RA, Sapin C, Peters-Strickland T, Beillat M, Nylander AG, Hertel P, Nitschky Schmidt S, Ettrup A, Eramo A, Hansen K, Naber D. Relationship between response to aripiprazole once-monthly and paliperidone palmitate on work readiness and functioning in schizophrenia: a post hoc analysis of the QUALIFY study. PLoS One. 2017;12(8):e0183475 (Correction: PLoS One. 2017;12(11):e0188416).Google Scholar
- 55.Potkin SG, Loze JY, Forray C, Baker RA, Sapin C, Peters-Strickland T, Beillat M, Nylander AG, Hertel P, Steen Andersen H, Eramo A, Hansen K, Naber D. Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY. Int Clin Psychopharmacol. 2017;32(3):147–54.CrossRefGoogle Scholar
- 56.Potkin SG, Loze JY, Forray C, Baker RA, Sapin C, Peters-Strickland T, Beillat M, Nylander AG, Hertel P, Nitschky Schmidt S, Eramo A, Hansen K, Naber D. Multidimensional assessment of functional outcomes in schizophrenia: results from QUALIFY, a head-to-head trial of aripiprazole once-monthly and paliperidone palmitate. Int J Neuropsychopharmacol. 2017;20(1):40–9.Google Scholar
- 61.Takekita Y, Koshikawa Y, Fabbri C, Sakai S, Sunada N, Onohara A, Nishida K, Yoshimura M, Kato M, Serretti A, Kinoshita T. Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial. BMC Psychiatry. 2016;16:172.Google Scholar