Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-17T14:09:19.746Z Has data issue: false hasContentIssue false
  • English
  • Français

Efficacy of lurasidone across five symptom dimensions of schizophrenia: Pooled analysis of short-term, placebo-controlled studies

Published online by Cambridge University Press:  15 April 2020

A. Loebel ,
J. Cucchiaro ,
R. Silva ,
Y. Mao ,
J. Xu ,
A. Pikalov  and
S.R. Marder
A. Loebel
Affiliation:
Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ07024, USA
J. Cucchiaro
Affiliation:
Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ07024, USA
R. Silva
Affiliation:
Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ07024, USA
Y. Mao
Affiliation:
Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ07024, USA
J. Xu
Affiliation:
Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ07024, USA
A. Pikalov
Affiliation:
Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ07024, USA
S.R. Marder*
Affiliation:
Semel Institute for Neuroscience at the University of California, Los Angeles, and the David Geffen School of Medicine, and the West Los Angeles VA Healthcare System, Building 210, Room 130, 11301 Wilshire Boulevard, Los Angeles, CA90073, USA
*
*Corresponding author. Tel.: +1 310 268 3647; fax: +1 310 268 4056. E-mail address:[email protected] (S.R. Marder).
Get access

Abstract

Objective:

To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).

Methods:

Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.

Results:

Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.

Conclusions:

In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.

Keywords

LurasidoneAtypical antipsychoticSchizophreniaFactor analysis
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 1 , January 2015 , pp. 26 - 31
Copyright
Copyright © Elsevier Masson SAS 2015

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association. Diagnostic and statistical manual of mental disordersWashington, DC: American Psychiatric Association; 2000.Google Scholar
Amore, M, Menchetti, M, Tonti, C, Scarlatti, F, Lundgren, E, Esposito, W, et al.Predictors of violent behavior among acute psychiatric patients: clinical study. Psychiatry Clin Neurosci 2008;62:247–255.CrossRefGoogle ScholarPubMed
Andreasen, NC, Olsen, S. Negative vs. positive schizophrenia. Definition and validation. Arch Gen Psychiatry 1982;39:789–794.CrossRefGoogle Scholar
Arndt, S, Andreasen, NC, Flaum, M, Miller, D, Nopoulos, P. A longitudinal study of symptom dimensions in schizophrenia. Prediction and patterns of change. Arch Gen Psychiatry 1995;52:352–360.CrossRefGoogle ScholarPubMed
Bell, MD, Lysaker, PH. Psychiatric symptoms and work performance among persons with severe mental illness. Psychiatr Serv 1995;46:508–510.Google ScholarPubMed
Bowie, CR, Reichenberg, A, Patterson, TL, Heaton, RK, Harvey, PD. Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms. Am J Psychiatry 2006;163:418–425.CrossRefGoogle ScholarPubMed
Buckley, PF, Miller, BJ, Lehrer, DS, Castle, DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009;35:383–402.CrossRefGoogle Scholar
Citrome, L, Meng, X, Hochfeld, M. Efficacy of iloperidone in schizophrenia: a PANSS five-factor analysis. Schizophr Res 2011;131:75–81.CrossRefGoogle ScholarPubMed
Conley, RR, Ascher-Svanum, H, Zhu, B, Faries, DE, Kinon, BJ. The burden of depressive symptoms in the long-term treatment of patients with schizophrenia. Schizophr Res 2007;90:186–197.CrossRefGoogle ScholarPubMed
Crow, TJ. Molecular pathology of schizophrenia: more than one disease process?. Br Med J 1980;280:66–68.CrossRefGoogle ScholarPubMed
Davis, JM, Chen, N. The effects of olanzapine on the 5 dimensions of schizophrenia derived by factor analysis: combined results of the North American and international trials. J Clin Psychiatry 2001;62:757–771.CrossRefGoogle ScholarPubMed
Erickson, M, Jaafari, N, Lysaker, P. Insight and negative symptoms as predictors of functioning in a work setting in patients with schizophrenia. Psychiatry Res 2011;189:161–165.CrossRefGoogle Scholar
Guy, W, US Department of Health, Education, Welfare Public Health Services Alcohol Drug Abuse, Mental Health Administration. ECDEU assessment manual for psychopharmacology revised, 1976. Rockville, MD: National Institute of Mental Health; 1976 76–338. [ADM]..Google Scholar
Harvey, PD, Heaton, RK, Carpenter, WT Jr., Green, MF, Gold, JM, Schoenbaum, M. Functional impairment in people with schizophrenia: focus on employability and eligibility for disability compensation. Schizophr Res 2012;140:1–8.CrossRefGoogle ScholarPubMed
Harvey, PD, Ogasa, M, Cucchiaro, J, Loebel, A, Keefe, RS. Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone. Schizophr Res 2011;127:188–194.CrossRefGoogle Scholar
Harvey, PD, Siu, CO, Hsu, J, Cucchiaro, J, Maruff, P, Loebel, A. Effect of lurasidone on neurocognitive performance in patients with schizophrenia: a short-term placebo- and active-controlled study followed by a 6-month double-blind extension. Eur Neuropsychopharmacol 2013;23:1373–1382.CrossRefGoogle ScholarPubMed
Horacek, J, Bubenikova-Valesova, V, Kopecek, M, Palenicek, T, Dockery, C, Mohr, P, et al.Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs 2006;20:389–409.CrossRefGoogle ScholarPubMed
Ishibashi, T, Horisawa, T, Tokuda, K, Ishiyama, T, Ogasa, M, Tagashira, R, et al.Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther 2010;334:171–181.CrossRefGoogle ScholarPubMed
Janicak, PG, Glick, ID, Marder, SR, Crandall, DT, McQuade, RD, Marcus, RN, et al.The acute efficacy of aripiprazole across the symptom spectrum of schizophrenia: a pooled post hoc analysis from 5 short-term studies. J Clin Psychiatry 2009;70:25–35.CrossRefGoogle ScholarPubMed
Jerrell, JM, Hrisko, S. A comparison of the PANSS pentagonal and Van Der Gaag 5-factor models for assessing change over time. Psychiatry Res 2013;207:134–139.CrossRefGoogle Scholar
Jin, H, Zisook, S, Palmer, BW, Patterson, TL, Heaton, RK, Jeste, DV. Association of depressive symptoms with worse functioning in schizophrenia: a study in older outpatients. J Clin Psychiatry 2001;62:797–803.CrossRefGoogle ScholarPubMed
Kane, JM, Cohen, M, Zhao, J, Alphs, L, Panagides, J. Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. J Clin Psychopharmacol 2010;30:106–115.CrossRefGoogle Scholar
Kapur, S, Zipursky, R, Jones, C, Remington, G, Houle, S. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000;157:514–520.CrossRefGoogle ScholarPubMed
Kasper, S. Optimisation of long-term treatment in schizophrenia: treating the true spectrum of symptoms. Eur Neuropsychopharmacol 2006;16:S135–S141.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle Scholar
Kessler, RC, Birnbaum, H, Demler, O, Falloon, IR, Gagnon, E, Guyer, M, et al.The prevalence and correlates of nonaffective psychosis in the National Comorbidity Survey Replication (NCS-R). Biol Psychiatry 2005;58:668–676.CrossRefGoogle Scholar
Kim, JH, Kim, SY, Lee, J, Oh, KJ, Kim, YB, Cho, ZH. Evaluation of the factor structure of symptoms in patients with schizophrenia. Psychiatry Res 2012;197:285–289.CrossRefGoogle ScholarPubMed
Lancon, C, Auquier, P, Nayt, G, Reine, G. Stability of the five-factor structure of the Positive and Negative Syndrome Scale (PANSS). Schizophr Res 2000;42:231–239.CrossRefGoogle Scholar
Leucht, S, Komossa, K, Rummel-Kluge, C, Corves, C, Hunger, H, Schmid, F, et al.A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry 2009;166:152–163.CrossRefGoogle ScholarPubMed
Lindenmayer, JP, Bernstein-Hyman, R, Grochowski, S. A new five factor model of schizophrenia. Psychiatr Q 1994;65:299–322.CrossRefGoogle ScholarPubMed
Lindenmayer, JP, Bernstein-Hyman, R, Grochowski, S, Bark, N. Psychopathology of schizophrenia: initial validation of a 5-factor model. Psychopathology 1995;28:22–31.CrossRefGoogle ScholarPubMed
Lindenmayer, JP, Czobor, P, Volavka, J, Lieberman, JA, Citrome, L, Sheitman, B, et al.Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia. J Clin Psychiatry 2004;65:551–556.CrossRefGoogle ScholarPubMed
Llorca, PM, Blanc, O, Samalin, L, Bosia, M, Cavallaro, R. Factors involved in the level of functioning of patients with schizophrenia according to latent variable modeling. Eur Psychiatry 2012;27:396–400.CrossRefGoogle ScholarPubMed
Loebel, A, Cucchiaro, J, Sarma, K, Xu, L, Hsu, C, Kalali, AH, et al.Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res 2013;145:101–109.CrossRefGoogle ScholarPubMed
Loebel, A, Cucchiaro, J, Silva, R, Kroger, H, Hsu, J, Sarma, K, et al.Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014;171:160–168.CrossRefGoogle ScholarPubMed
Loebel, A, Cucchiaro, J, Silva, R, Kroger, H, Xu, J, Calabrese, JR. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014;171:169–177.CrossRefGoogle ScholarPubMed
Marder, SR, Davis, JM, 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.CrossRefGoogle ScholarPubMed
Meltzer, HY, Cucchiaro, J, Silva, R, Ogasa, M, Phillips, D, Xu, J, et al.Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry 2011;168:957–967.CrossRefGoogle ScholarPubMed
Nakamura, M, Ogasa, M, Guarino, J, Phillips, D, Severs, J, Cucchiaro, J, et al.Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2009;70:829–836.CrossRefGoogle ScholarPubMed
Nakaya, M, Suwa, H, Ohmori, K. Latent structures underlying schizophrenic symptoms: a five-dimensional model. Schizophr Res 1999;39:39–50.CrossRefGoogle ScholarPubMed
Nasrallah, HA, Cucchiaro, JB, Mao, Y, Pikalov, AA, Loebel, AD. Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-week, placebo-controlled studies. CNS Spectr 2014;23:1–8.Google Scholar
Nasrallah, HA, Silva, R, Phillips, D, Cucchiaro, J, Hsu, J, Xu, J, et al.Lurasidone for the treatment of acutely psychotic patients with schizophrenia: a 6-week, randomized, placebo-controlled study. J Psychiatr Res 2013;47:670–677.CrossRefGoogle ScholarPubMed
Nolan, KA, Volavka, J, Czobor, P, Sheitman, B, Lindenmayer, JP, Citrome, LL, et al.Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder. J Psychiatr Res 2005;39:109–115.CrossRefGoogle ScholarPubMed
Ogasa, M, Kimura, T, Nakamura, M, Guarino, J. Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study. Psychopharmacology (Berl) 2013;225:519–530.CrossRefGoogle ScholarPubMed
Overall, JE, Gorha, DRThe brief psychiatric rating scale. Psychol Rep 1962;799–812.CrossRefGoogle Scholar
Pandina, G, Bilder, R, Turkoz, I, Alphs, L. Identification of clinically meaningful relationships among cognition, functionality, and symptoms in subjects with schizophrenia or schizoaffective disorder. Schizophr Res 2013;143:312–318.CrossRefGoogle ScholarPubMed
Peralta, V, Cuesta, MJ. How many and which are the psychopathological dimensions in schizophrenia? Issues influencing their ascertainment. Schizophr Res 2001;49:269–285.CrossRefGoogle ScholarPubMed
Potkin, SG, Keator, DB, Kesler-West, ML, Nguyen, DD, van Erp, TG, Mukherjee, J, et al.D2 receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder. CNS Spectr 2014;19:176–181.CrossRefGoogle ScholarPubMed
Potkin, SG, Phiri, P, Szegedi, A, Zhao, J, Alphs, L, Cazorla, P. Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis. Schizophr Res 2013;150:442–449.CrossRefGoogle ScholarPubMed
Rabinowitz, J, Levine, SZ, Garibaldi, G, Bugarski-Kirola, D, Berardo, CG, Kapur, S. Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: analysis of CATIE data. Schizophr Res 2012;137:147–150.CrossRefGoogle ScholarPubMed
Reine, G, Lançon, C, Di Tucci, S, Sapin, C, Auquier, P. Depression and subjective quality of life in chronic phase schizophrenic patients. Acta Psychiatr Scand 2003;108:297–303.CrossRefGoogle ScholarPubMed
Sands, JR, Harrow, M. Depression during the longitudinal course of schizophrenia. Schizophr Bull 1999;25:157–171.CrossRefGoogle ScholarPubMed
Schwartz, RC, Cohen, BN. Psychosocial correlates of suicidal intent among patients with schizophrenia. Compr Psychiatry 2001;42:118–123.CrossRefGoogle ScholarPubMed
Siris, SG. Depression in schizophrenia: perspective in the era of “atypical” antipsychotic agents. Am J Psychiatry 2000;157:1379–1389.CrossRefGoogle ScholarPubMed
Siris, SG. Suicide and schizophrenia. J Psychopharmacol 2001;15:127–135.CrossRefGoogle Scholar
Soyka, M, Graz, C, Bottlender, R, Dirschedl, P, Schoech, H. Clinical correlates of later violence and criminal offences in schizophrenia. Schizophr Res 2007;94:89–98.CrossRefGoogle Scholar
Swanson, JW, Swartz, MS, Van Dorn, RA, Elbogen, EB, Wagner, HR, Rosenheck, RA, et al.A national study of violent behavior in persons with schizophrenia. Arch Gen Psychiatry 2006;63:490–499.CrossRefGoogle ScholarPubMed
van der Gaag, M, Hoffman, T, Remijsen, M, Hijman, R, de, HL, van, MB, et al.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.CrossRefGoogle ScholarPubMed
Velligan, DI, Alphs, L, Lancaster, S, Morlock, R, Mintz, J. Association between changes on the Negative Symptom Assessment scale (NSA-16) and measures of functional outcome in schizophrenia. Psychiatry Res 2009;169:97–100.CrossRefGoogle Scholar
Ventura, J, Hellemann, GS, Thames, AD, Koellner, V, Nuechterlein, KH. Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophr Res 2009;113:189–199.CrossRefGoogle ScholarPubMed
Vos, T, Flaxman, AD, Naghavi, M, Lozano, R, Michaud, C, Ezzati, M, et al.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.CrossRefGoogle ScholarPubMed
Wallwork, RS, Fortgang, R, Hashimoto, R, Weinberger, DR, Dickinson, D. Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia. Schizophr Res 2012;137:246–250.CrossRefGoogle Scholar
Wiersma, D, Wanderling, J, Dragomirecka, E, Ganev, K, Harrison, G, an der, HW, et al.Social disability in schizophrenia: its development and prediction over 15 years in incidence cohorts in six European centres. Psychol Med 2000;30:1155–1167.CrossRefGoogle ScholarPubMed
Wong, DF, Kuwabara, H, Brasic, JR, Stock, T, Maini, A, Gean, EG, et al.Determination of dopamine D receptor occupancy by lurasidone using positron emission tomography in healthy male subjects. Psychopharmacology (Berl) 2013;229:245–252.CrossRefGoogle ScholarPubMed
World Health, , Organization, The global burden of disease: 2004 update. Geneva, Switzerland: World Health Organization; 2008 [Accessed February 14, 2013] http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf.Google Scholar
Submit a response

Comments

No Comments have been published for this article.