A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia

Schizophrenia Research

Volumn 164, Issue 1-3, 2015, Pages 127-135

  Kane, John M ^a   Skuban, Aleksandar ^b   Ouyang, John ^b   Hobart, Mary ^b   Pfister, Stephanie ^b   McQuade, Robert D ^b   Nyilas, Margaretta ^b   Carson, William H ^b   Sanchez, Raymond ^b   Eriksson, Hans ^c  

^a ZUCKER HILLSIDE HOSPITAL   (United States)

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

^c H LUNDBECK A S   (Denmark)

Author keywords

Acute; Brexpiprazole; Efficacy; Phase 3 trial; Safety; Schizophrenia

Indexed keywords

BREXPIPRAZOLE; PLACEBO; QUINOLONE DERIVATIVE; SEROTONIN RECEPTOR AFFECTING AGENT; THIOPHENE DERIVATIVE;

ACUTE PSYCHOSIS; ADULT; AGGRESSION; AGITATION; AKATHISIA; ANXIETY; ARTICLE; CLINICAL GLOBAL IMPRESSION SCALE; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FEMALE; FOLLOW UP; HALLUCINATION; HEADACHE; HUMAN; INSOMNIA; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OUTCOME ASSESSMENT; PHASE 3 CLINICAL TRIAL; POSITIVE AND NEGATIVE SYNDROME SCALE; PRIORITY JOURNAL; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL; RESTLESSNESS; SCHIZOPHRENIA; SIDE EFFECT; SOMNOLENCE; SUICIDE; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VITAL SIGN; WEIGHT GAIN; ADOLESCENT; CLINICAL TRIAL; MIDDLE AGED; NEUROPSYCHOLOGICAL TEST; PSYCHOLOGICAL RATING SCALE; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; PSYCHIATRIC STATUS RATING SCALES; QUINOLONES; SCHIZOPHRENIA; SEROTONIN AGENTS; THIOPHENES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84928640856     PISSN: 09209964     EISSN: 15732509     Source Type: Journal    
DOI: 10.1016/j.schres.2015.01.038     Document Type: Article

References (34)

1. Barnes T.R. A rating scale for drug-induced akathisia. Br. J. Psychiatry 1989, 154:672-676.
2. Bobes J., Garcia-Portilla M.P., Bascaran M.T., Saiz P.A., Bousono M. Quality of life in schizophrenic patients. Dialogues Clin. Neurosci. 2007, 9:215-226.
3. Chappell P., Feltner D.E., Makumi C., Stewart M. Initial validity and reliability data on the Columbia-Suicide Severity Rating Scale. Am. J. Psychiatry 2012, 169:662-663.
4. Correll C.U. From receptor pharmacology to improved outcomes: individualising the selection, dosing, and switching of antipsychotics. Eur. Psychiatry 2010, 25(Suppl. 2):S12-S21.
5. De Hert M., Detraux J., van Winkel R., Yu W., Correll C.U. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat. Rev. Endocrinol. 2012, 8:114-126.
6. Fleischhacker W.W. Aripiprazole. Expert. Opin. Pharmacother. 2005, 6:2091-2101.
7. Gharabawi G., Bossie C., Turkoz I., Kujawa M., Mahmoud R., Simpson G. The impact of insight on functioning in patients with schizophrenia or schizoaffective disorder receiving risperidone long-acting injectable. J. Nerv. Ment. Dis. 2007, 195:976-982.
8. Guy W. ECDEU Assessment Manual for Psychopharmacology (revised). US Department of Health, Education, and Welfare publication (ADM) 76-338 1976, 193-198. National Institute of, Mental Health, Rockville, MD.
9. Kane J.M., Correll C.U. Past and present progress in the pharmacologic treatment of schizophrenia. J. Clin. Psychiatry 2010, 71:1115-1124.
10. Kane J.M., Fleischhacker W.W., Hansen L., Perlis R., Pikalov A., Assuncao-Talbott S. Akathisia: an updated review focusing on second-generation antipsychotics. J. Clin. Psychiatry 2009, 70:627-643.
11. Kay S.R., Opler L.A., Fiszbein A. Positive and negative syndrome scale (PANSS) rating criteria Multi-Health Systems, North Tonawanda, NY 1999.
12. Laoutidis Z.G., Kioulos K.T. Antipsychotic-induced elevation of creatine kinase: a systematic review of the literature and recommendations for the clinical practice. Psychopharmacology (Berl) 2014, 231:4255-4270.
13. Leucht S. Measurements of response, remission, and recovery in schizophrenia and examples for their clinical application. J. Clin. Psychiatry 2014, 75(Suppl. 1):8-14.
14. Leucht S., Cipriani A., Spineli L., Mavridis D., Orey D., Richter F., Samara M., Barbui C., Engel R.R., Geddes J.R., Kissling W., Stapf M.P., Lassig B., Salanti G., Davis J.M. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013, 382:951-962.
15. Lieberman J.A., Perkins D., Belger A., Chakos M., Jarskog F., Boteva K., Gilmore J. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol. Psychiatry 2001, 50:884-897.
16. Lindenmayer J.P., Bernstein-Hyman R., Grochowski S., Bark N. Psychopathology of Schizophrenia: initial validation of a 5-factor model. Psychopathology 1995, 28:22-31.
17. Maeda K., Lerdrup L., Sugino H., Akazawa H., Amada N., McQuade R.D., Stensbol T.B., Bundgaard C., Arnt J., Kikuchi T. Brexpiprazole II: antipsychotic-like and pro-cognitive effects of a novel serotonin-dopamine activity modulator. J. Pharmacol. Exp. Ther. 2014, 350:605-614.
18. Maeda K., Sugino H., Akazawa H., Amada N., Shimada J., Futamura T., Yamashita H., Ito N., McQuade R.D., Mork A., Pehrson A.L., Hentzer M., Nielsen V., Bundgaard C., Arnt J., Stensbol T.B., Kikuchi T. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J. Pharmacol. Exp. Ther. 2014, 350:589-604.
19. Marder S.R., Davis J.M., Chouinard G. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J. Clin. Psychiatry 1997, 58:538-546.
20. McGrath J., Saha S., Chant D., Welham J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol. Rev. 2008, 30:67-76.
21. Melkersson K. Serum creatine kinase levels in chronic psychosis patients-a comparison between atypical and conventional antipsychotics. Prog. Neuropsychopharmacol. Biol. Psychiatry 2006, 30:1277-1282.
22. Messias E.L., Chen C.Y., Eaton W.W. Epidemiology of schizophrenia: review of findings and myths. Psychiatr. Clin. North Am. 2007, 30:323-338.
23. Montoya A., Valladares A., Lizan L., San L., Escobar R., Paz S. 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 2011, 9:18. 10.1186/1477-7525-9-18.
24. Morosini P.L., Magliano L., Brambilla L., Ugolini S., Pioli R. 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. 2000, 101:323-329.
25. Nakaya M., Suwa H., Ohmori K. Latent structures underlying schizophrenic symptoms: a five-dimensional model. Schizophr. Res. 1999, 39:39-50.
26. Posner K., Brown G.K., Stanley B., Brent D.A., Yershova K.V., Oquendo M.A., Currier G.W., Melvin G.A., Greenhill L., Shen S., Mann J.J. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am. J. Psychiatry 2011, 168:1266-1277.
27. Potkin S.G., Raoufinia A., Mallikaarjun S., Bricmont P., Peters-Strickland T., Kasper W., Baker R.A., Eramo A., Sanchez R., McQuade R. Safety and tolerability of once monthly aripiprazole treatment initiation in adults with schizophrenia stabilized on selected atypical oral antipsychotics other than aripiprazole. Curr. Med. Res. Opin. 2013, 29:1241-1251.
28. Salomon J.A., Vos T., Hogan D.R., Gagnon M., Naghavi M., Mokdad A., Begum N., Shah R., Karyana M., Kosen S., Farje M.R., Moncada G., Dutta A., Sazawal S., Dyer A., Seiler J., Aboyans V., Baker L., Baxter A., Benjamin E.J., Bhalla K., Bin A.A., Blyth F., Bourne R., Braithwaite T., Brooks P., Brugha T.S., Bryan-Hancock C., Buchbinder R., Burney P., Calabria B., Chen H., Chugh S.S., Cooley R., Criqui M.H., Cross M., Dabhadkar K.C., Dahodwala N., Davis A., Degenhardt L., Diaz-Torne C., Dorsey E.R., Driscoll T., Edmond K., Elbaz A., Ezzati M., Feigin V., Ferri C.P., Flaxman A.D., Flood L., Fransen M., Fuse K., Gabbe B.J., Gillum R.F., Haagsma J., Harrison J.E., Havmoeller R., Hay R.J., Hel-Baqui A., Hoek H.W., Hoffman H., Hogeland E., Hoy D., Jarvis D., Karthikeyan G., Knowlton L.M., Lathlean T., Leasher J.L., Lim S.S., Lipshultz S.E., Lopez A.D., Lozano R., Lyons R., Malekzadeh R., Marcenes W., March L., Margolis D.J., McGill N., McGrath J., Mensah G.A., Meyer A.C., Michaud C., Moran A., Mori R., Murdoch M.E., Naldi L., Newton C.R., Norman R., Omer S.B., Osborne R., Pearce N., Perez-Ruiz F., Perico N., Pesudovs K., Phillips D., Pourmalek F., Prince M., Rehm J.T., Remuzzi G., Richardson K., Room R., Saha S., Sampson U., Sanchez-Riera L., Segui-Gomez M., Shahraz S., Shibuya K., Singh D., Sliwa K., Smith E., Soerjomataram I., Steiner T., Stolk W.A., Stovner L.J., Sudfeld C., Taylor H.R., Tleyjeh I.M., van der Werf M.J., Watson W.L., Weatherall D.J., Weintraub R., Weisskopf M.G., Whiteford H., Wilkinson J.D., Woolf A.D., Zheng Z.J., Murray C.J., Jonas J.B. Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010. Lancet 2012, 380:2129-2143.
29. Simpson G.M., Angus J.W. A rating scale for extrapyramidal side effects. Acta Psychiatr. Scand. Suppl. 1970, 212:11-19.
30. Stip E., Tourjman V. Aripiprazole in schizophrenia and schizoaffective disorder: a review. Clin. Ther. 2010, 32(Suppl. 1):S3-S20.
31. van der Gaag M., Hoffman T., Remijsen M., Hijman R., de H.L., van Meijel B., van Harten P.N., Valmaggia L., de Hert M., Cuijpers A., Wiersma D. The five-factor model of the Positive and Negative Syndrome Scale II: a ten-fold cross-validation of a revised model. Schizophr. Res. 2006, 85:280-287.
32. von Knorring L., Lindstrom E. Principal components and further possibilities with the PANSS. Acta Psychiatr. Scand. Suppl. 1995, 388:5-10.
33. Vos T., Flaxman A.D., Naghavi M., Lozano R., Michaud C., Ezzati M., Shibuya K., Salomon J.A., Abdalla S., Aboyans V., Abraham J., Ackerman I., Aggarwal R., Ahn S.Y., Ali M.K., Alvarado M., Anderson H.R., Anderson L.M., Andrews K.G., Atkinson C., Baddour L.M., Bahalim A.N., Barker-Collo S., Barrero L.H., Bartels D.H., Basanez M.G., Baxter A., Bell M.L., Benjamin E.J., Bennett D., Bernabe E., Bhalla K., Bhandari B., Bikbov B., Bin A.A., Birbeck G., Black J.A., Blencowe H., Blore J.D., Blyth F., Bolliger I., Bonaventure A., Boufous S., Bourne R., Boussinesq M., Braithwaite T., Brayne C., Bridgett L., Brooker S., Brooks P., Brugha T.S., Bryan-Hancock C., Bucello C., Buchbinder R., Buckle G., Budke C.M., Burch M., Burney P., Burstein R., Calabria B., Campbell B., Canter C.E., Carabin H., Carapetis J., Carmona L., Cella C., Charlson F., Chen H., Cheng A.T., Chou D., Chugh S.S., Coffeng L.E., Colan S.D., Colquhoun S., Colson K.E., Condon J., Connor M.D., Cooper L.T., Corriere M., Cortinovis M., de Vaccaro K.C., Couser W., Cowie B.C., Criqui M.H., Cross M., Dabhadkar K.C., Dahiya M., Dahodwala N., Damsere-Derry J., Danaei G., Davis A., De L.D., Degenhardt L., Dellavalle R., Delossantos A., Denenberg J., Derrett S., Des Jarlais D.C., Dharmaratne S.D., Dherani M., Diaz-Torne C., Dolk H., Dorsey E.R., Driscoll T., Duber H., Ebel B., Edmond K., Elbaz A., Ali S.E., Erskine H., Erwin P.J., Espindola P., Ewoigbokhan S.E., Farzadfar F., Feigin V., Felson D.T., Ferrari A., Ferri C.P., Fevre E.M., Finucane M.M., Flaxman S., Flood L., Foreman K., Forouzanfar M.H., Fowkes F.G., Franklin R., Fransen M., Freeman M.K., Gabbe B.J., Gabriel S.E., Gakidou E., Ganatra H.A., Garcia B., Gaspari F., Gillum R.F., Gmel G., Gosselin R., Grainger R., Groeger J., Guillemin F., Gunnell D., Gupta R., Haagsma J., Hagan H., Halasa Y.A., Hall W., Haring D., Haro J.M., Harrison J.E., Havmoeller R., Hay R.J., Higashi H., Hill C., Hoen B., Hoffman H., Hotez P.J., Hoy D., Huang J.J., Ibeanusi S.E., Jacobsen K.H., James S.L., Jarvis D., Jasrasaria R., Jayaraman S., Johns N., Jonas J.B., Karthikeyan G., Kassebaum N., Kawakami N., Keren A., Khoo J.P., King C.H., Knowlton L.M., Kobusingye O., Koranteng A., Krishnamurthi R., Lalloo R., Laslett L.L., Lathlean T., Leasher J.L., Lee Y.Y., Leigh J., Lim S.S., Limb E., Lin J.K., Lipnick M., Lipshultz S.E., Liu W., Loane M., Ohno S.L., Lyons R., Ma J., Mabweijano J., MacIntyre M.F., Malekzadeh R., Mallinger L., Manivannan S., Marcenes W., March L., Margolis D.J., Marks G.B., Marks R., Matsumori A., Matzopoulos R., Mayosi B.M., McAnulty J.H., McDermott M.M., McGill N., McGrath J., Medina-Mora M.E., Meltzer M., Mensah G.A., Merriman T.R., Meyer A.C., Miglioli V., Miller M., Miller T.R., Mitchell P.B., Mocumbi A.O., Moffitt T.E., Mokdad A.A., Monasta L., Montico M., Moradi-Lakeh M., Moran A., Morawska L., Mori R., Murdoch M.E., Mwaniki M.K., Naidoo K., Nair M.N., Naldi L., Narayan K.M., Nelson P.K., Nelson R.G., Nevitt M.C., Newton C.R., Nolte S., Norman P., Norman R., O'Donnell M., O'Hanlon S., Olives C., Omer S.B., Ortblad K., Osborne R., Ozgediz D., Page A., Pahari B., Pandian J.D., Rivero A.P., Patten S.B., Pearce N., Padilla R.P., Perez-Ruiz F. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380:2163-2196.
34. Whiteford H.A., Degenhardt L., Rehm J., Baxter A.J., Ferrari A.J., Erskine H.E., Charlson F.J., Norman R.E., Flaxman A.D., Johns N., Burstein R., Murray C.J., Vos T. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 2013, 382:1575-1586.