Efficacy and safety of brexpiprazole (OPC-34712) as maintenance treatment in adults with schizophrenia: A randomized, double-blind, placebo-controlled study

International Journal of Neuropsychopharmacology

Volumn 20, Issue 1, 2017, Pages 11-21

  Fleischhacker, W Wolfgang ^a   Hobart, Mary ^b   Ouyang, John ^b   Forbes, Andy ^b   Pfister, Stephanie ^b   McQuade, Robert D ^b   Carson, William H ^b   Sanchez, Raymond ^b   Nyilas, Margareta ^b   Weiller, Emmanuelle ^c  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b OTSUKA PHARMACEUTICAL DEVELOPMENT AND COMMERCIALIZATION INC   (United States)

^c H LUNDBECK A S   (Denmark)

Author keywords

Brexpiprazole; Maintenance; Relapse; Schizophrenia; Stabilization

Indexed keywords

BREXPIPRAZOLE; PLACEBO; TRIACYLGLYCEROL; NEUROLEPTIC AGENT; QUINOLONE DERIVATIVE; THIOPHENE DERIVATIVE;

ADULT; ADULT DISEASE; AGED; AGITATION; AKATHISIA; ARTICLE; CONTROLLED STUDY; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG STABILITY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEMALE; FOLLOW UP; HEADACHE; HUMAN; INCIDENCE; INSOMNIA; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SCHIZOPHRENIA; SIDE EFFECT; WEIGHT GAIN; BODY WEIGHT DISORDER; GLOBAL ASSESSMENT OF FUNCTIONING; GUNSHOT INJURY; PERSONAL AND SOCIAL PERFORMANCE SCORE; POSITIVE AND NEGATIVE SYNDROME SCALE; RELAPSE; SECONDARY ANALYSIS; SINGLE BLIND PROCEDURE; SUICIDE ATTEMPT; TRIACYLGLYCEROL LEVEL; ADOLESCENT; CLINICAL TRIAL; MIDDLE AGED; PROPORTIONAL HAZARDS MODEL; PSYCHOLOGICAL RATING SCALE; RECURRENT DISEASE; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTIPSYCHOTIC AGENTS; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; MIDDLE AGED; PROPORTIONAL HAZARDS MODELS; PSYCHIATRIC STATUS RATING SCALES; QUINOLONES; RECURRENCE; SCHIZOPHRENIA; THIOPHENES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 85012306014     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1093/ijnp/pyw076     Document Type: Article

References (44)

1. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th ed., text revision (DSMIV-TR). Arlington, VA: American Psychiatric Association.
2. Ascher-Svanum H, Zhu B, Faries DE, Salkever D, Slade EP, Peng X, Conley RR (2010) The cost of relapse and the predictors of relapse in the treatment of schizophrenia. BMC Psychiatry 10: 1-7.
3. Barnes TR (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154: 672-676.
4. Bowie CR, Harvey PD (2006) Cognitive deficits and functional outcome in schizophrenia. Neuropsychiatr Dis Treat 2: 531-536.
5. Burns T, Patrick D (2007) Social functioning as an outcome measure in schizophrenia studies. Acta Psychiatr Scand 116: 403-418.
6. Carpenter WT Jr, Appelbaum PS, Levine RJ (2003) The Declaration of Helsinki and clinical trials: a focus on placebo-controlled trials in schizophrenia. Am J Psychiatry 160: 356-362.
7. ClinicalTrials.gov (2014) PEARL Schizophrenia Maintenance. ClinicalTrials.gov Identifier: NCT01435928. Available at: https://clinicaltrials.gov/ct2/show/NCT01435928. Accessed 25 April 2016.
8. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers.
9. Correll CU, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H (2015) Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: a 6-week randomized, double-blind, placebocontrolled trial. Am J Psychiatry 172: 870-880.
10. Csernansky JG, Mahmoud R, Brenner R; Risperidone-USA-79 Study Group (2002) A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 346: 16-22.
11. Désaméricq G, Schurhoff F, Meary A, Szöke A, Macquin-Mavier I, Bachoud-Lévi AC, Maison P (2014) Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. Eur J Clin Pharmacol 70: 127-134.
12. Emsley R, Chiliza B, Asmal L, Harvey BH (2013) The nature of relapse in schizophrenia. BMC Psychiatry 13: 50.
13. Emsley R, Fleischhacker WW (2013) Is the ongoing use of placebo in relapse-prevention clinical trials in schizophrenia justified? Schizophr Res 150: 427-433.
14. European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) (2012) Guideline on clinical investigation of medicinal products, including depot preparations in the treatment of schizophrenia. EMA/CHMP/40072/2010 Rev. 1. Available at: http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2012/10/WC500133437.pdf. Accessed 25 April 2016.
15. Fatouros-Bergman H, Cervenka S, Flyckt L, Edman G, Farde L (2014) Meta-analysis of cognitive performance in drug-naïve patients with schizophrenia. Schizophr Res 158: 156-162.
16. 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 (2014) Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study. Br J Psychiatry 205: 135-144.
17. Guy W (1976) ECDEU assessment manual for psychopharmacology, revised. Rockville, MD: National Institute of Mental Health.
18. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ; WFSBP Task force on Treatment Guidelines for Schizophrenia (2013) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the longterm treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 14: 2-44.
19. Hough D, Gopal S, Vijapurkar U, Lim P, Morozova M, Eerdekens M (2010) Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res 116: 107-117.
20. Ishigooka J, Nakamura J, Fujii Y, Iwata N, Kishimoto T, Iyo M, Uchimura N, Nishimura R, Shimizu N; ALPHA Study Group (2015) 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 161: 421-428.
21. Kane JM (2007) Treatment strategies to prevent relapse and encourage remission. J Clin Psychiatry 68: 27-30.
22. Kane JM, Sanchez R, Perry PP, Jin N, Johnson BR, Forbes RA, McQuade RD, Carson WH, Fleischhacker WW (2012) Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 73: 617-624.
23. Kane JM, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H (2015) A multicenter, randomized, double-blind, controlled Phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res 164: 127-135.
24. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13: 261-276.
25. Kramer M, Simpson G, Maciulis V, Kushner S, Vijapurkar U, Lim P, Eerdekens M (2007) Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 27: 6-14.
26. Kumar R, Sachdev PS (2009) Akathisia and second-generation antipsychotic drugs. Curr Opin Psychiatry 22: 293-299.
27. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J; American Psychiatric Association; Steering Committee on Practice Guidelines (2004) Practice guideline for the treatment of patients with schizophrenia, 2nd ed. Am J Psychiatry 161: 1-56.
28. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 379: 2063-2071.
29. Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382: 951-962.
30. Maeda K, Sugino H, Akazawa H, Amada N, Shimada J, Futamura T, Yamashita H, Ito N, McQuade RD, Mørk A, Pehrson AL, Hentzer M, Nielsen V, Bundgaard C, Arnt J, Stensbøl TB, Kikuchi T (2014) Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther 350: 589-604.
31. Marder SR, Davis JM, Chouinard G (1997) The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry 58: 538-546.
32. Maruff P, Thomas E, Cysique L, Brew B, Collie A, Snyder P, Pietrzak RH (2009) Validity of the CogState brief battery: relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch Clin Neuropsychol 24: 165-178.
33. McGrath J, Saha S, Chant D, Welham J (2008) Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev 30: 67-76.
34. Montoya A, Valladares A, Lizán L, San L, Escobar R, Paz S (2011) Validation of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a naturalistic sample of 278 patients with acute psychosis and agitation in a psychiatric emergency room. Health Qual Life Outcomes 9: 18.
35. Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R (2000) Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand 101: 323-329.
36. Nasrallah H, Morosini P, Gagnon DD (2008) Reliability, validity and ability to detect change of the Personal and Social Performance scale in patients with stable schizophrenia. Psychiatry Res 161: 213-224.
37. Nielsen RE, Levander S, Kjaersdam Telléus G, Jensen SO, Østergaard Christensen T, Leucht S (2015) Second-generation antipsychotic effect on cognition in patients with schizophrenia - a meta-analysis of randomized clinical trials. Acta Psychiatr Scand 131: 185-196.
38. Pietrzak RH, Olver J, Norman T, Piskulic D, Maruff P, Snyder PJ (2009) A comparison of the CogState Schizophrenia Battery and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery in assessing cognitive impairment in chronic schizophrenia. J Clin Exp Neuropsychol 31: 848-859.
39. Pigott TA, Carson WH, Saha AR, Torbeyns AF, Stock EG, Ingenito GG; Aripiprazole Study Group (2003) Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study. J Clin Psychiatry 64: 1048-1056.
40. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ (2011) The Columbia - Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 168: 1266-1277.
41. Sampson S, Joshi K, Mansour M, Adams CE (2013) Intermittent drug techniques for schizophrenia. Schizophr Bull 39: 960-961.
42. Simpson GM, Angus JW (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 212: 11-19.
43. nd European Congress of Psychiatry. Eur Psychiatry 29(Suppl 1): 1-1407.
44. U.S. Department of Health and Human Services Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH) (2012) Draft guidance for industry. Enrichment strategies for clinical trials to support approval of human drugs and biological products. Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm332181.pdf. Accessed 25 April 2016.