Flexible dosing with paliperidone ER in the treatment of patients with acutely exacerbated schizophrenia: results from a single-arm, open-label study

Abstract

Objective:

To extend findings from fixed-dose, double-blind, placebo-controlled clinical trials in selected patient populations by using flexibly-dosed oral paliperidone extended-release (ER) in a more naturalistic setting.

Methods:

Adults hospitalized with an acute exacerbation of schizophrenia were prospectively treated with open-label flexibly-dosed paliperidone ER 3–12 mg/day for 6 weeks.

Results:

Overall, 294 patients were treated. The primary endpoint, defined as ≥30% improvement in Positive and Negative Syndrome Scale total scores from baseline to endpoint, was achieved by 66.3% of patients. The percentage of patients rated as at least ‘markedly ill’ in Clinical Global Impression of Severity scale decreased from baseline (74.1%) to endpoint (20.0%). Patient functioning, assessed by the Personal and Social Performance scale, improved significantly from 50.0 ± 14.3 at baseline to 63.6 ± 14.9 at endpoint (p < 0.0001). Concomitant benzodiazepines were newly initiated in 191 patients (65.0%), and new concomitant medications other than benzodiazepines were started after baseline for 133 patients (45.2%), most frequently paracetamol, zolpidem, and zopiclone. No unexpected adverse events were identified.

Conclusions:

These data support findings in more selected patient populations treated with fixed-dose paliperidone ER. Flexibly-dosed paliperidone ER administered in a naturalistic hospital setting to a more representative patient population experiencing an acute episode of schizophrenia, was associated with clinically meaningful treatment response. Strength of conclusions is limited by the open-label design and lack of a comparator group. Furthermore, some of the improvements observed may in part be associated with increased attention provided to patients and concomitant use of psychotropic medications, such as benzodiazepines, during this study.

Key words::

• Extended release
• Flexible dosing
• Paliperidone
• Schizophrenia

Transparency

Declaration of funding

The study, writing and editorial support were funded by Janssen Pharmaceutical Companies of Johnson & Johnson in EMEA.

Janssen Pharmaceutical Company of Johnson & Johnson in EMEA was involved in the study design; data collection, analysis, and interpretation; manuscript preparation; and the decision to submit the paper for publication.

This study was designed and the protocol written by Andreas Schreiner and Dagmar Hoeben. Data collection and analysis were performed by Janssen Pharmaceutical Companies of Johnson & Johnson in EMEA. Statistical support was provided by Marjolein Lahaye. The other authors were investigators in the clinical study. All authors have contributed to and approved the final manuscript. The manuscript was prepared by Excerpta Medica, funded by Janssen Pharmaceutical Companies.

Declaration of financial/other relationships

M.S. is a member of the advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Lundbeck, GlaxoSmithKline, Janssen-Cilag, and Otsuka; and a member of the speakers’ bureau for AstraZeneca, Bristol-Myers Squibb, Esparma, GlaxoSmithKline, Lundbeck, Janssen-Cilag, Merz Pharmaceuticals, Otsuka, and Pfizer Pharma. A.S. has received research support from AstraZeneca, Pfizer, and Eli Lilly. He has been also a consultant for Janssen-Cilag, as well as on the speakers’ bureau of Eli Lilly, Lundbeck, and Pfizer. L.B. has received research grants from Eli Lilly and has given industry-sponsored lectures for Eli Lilly, Janssen-Cilag, Lundbeck, Novartis, Pfizer, KRKA, and Sanofi-Aventis. G.M.B. has no conflicts of interest. M.L. is an employee of Janssen-Cilag BV, Netherlands. D.H. was an employee and former member of Medical Affairs EMEA at Janssen Pharmaceutica NV, Belgium. C.T. was an employee and former member of Medical Affairs EMEA at Janssen-Cilag SAS, France. A.S. is an employee and a member of Medical Affairs EMEA at Janssen-Cilag GmbH, Germany, and is shareholder of Johnson & Johnson. V.M. and V.J. have no conflicts of interest.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors would like to thank Tam Vo, PhD, and a team from Excerpta Medica for providing writing and editorial support.

Participating sites

Vlado Jukic, PB ‘VRAPCE’, Zagreb, Croatia; Miroslav Herceg, PB ‘VRAPCE’, Zagreb, Croatia; Darko Perusic, PB ‘VRAPCE’ Zagreb, Croatia; Vesna Dominis, Psychiatric Hospital ‘Sv. Ivan’, Zagreb, Croatia; Beatrice Beaufils, Hôpital Corentin Celton, Issy Les Moulineaux, France; Michel Blanc, C.H. Jury-les-Metz, Metz, France; Didier Feray, Centre Hospitalier de Dieppe, Dieppe N/a, France; Nicole Valliant, CHS La Charite Sur Loire, La Charite Sur Loire, France; Sabine Herpertz, Universität Rostock, Rostock, Germany; Gerd Laux, Bezirksklinikum Gabersee, Wasserburg, Germany; Wolfgang Maier, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Bonn, Germany; Max Schmauss, BKH Augsburg, Augsburg, Germany; Thomas Dielentheis, Klinikum der Johannes Gutenberg Universität Psychiatrisch Klinik und Poliklinik, Mainz, Germany; Stephan Heres, TU München, Germany; Mathias Zink, Zentralinstitut für Seelische Gesundheit, Mannheim, Germany; Moshe Kotler, Be’er Ya’acov Mental Health Center, Be’er Ya’acov, Israel; Hagai Haari, Shalvata Mental Health Center, Hod-Hasharon, Israel; Asaf Caspi, Sheba MC Tel Hashomer, Ramat Gan, Israel; Orit Stein Reisner, Lev Hasharon Mental Health Center, Pardesia, Israel; Zeev Kaplan, Be’er Sheva Mental Health Center, Be’er Sheva, Israel; Alberto Siracusano, Unità Operativa Complessa di Psichiatria, Università degli Studi di Roma Tor Vergata– Psychiatry, Roma, Italy; Cinzia Niolu, Unità Operativa Complessa di Psichiatria, Università degli Studi di Roma Tor Vergata– Psychiatry, Roma, Italy; Marco Grignani, SPCD Policlinico Monteluce – Psychiatry, Perugia, Italy; Gianmarco Polselli, Dipartimento di Psichiatria, Roma, Italy; Valentinas Maciulis, Republican Vilnius Psychiatric Hospital, Vilnius, Lithuania; Beata Urboniene, Vilnius Mental Health Center, Vilnius, Lithuania; Eugenijus Mikaliunas, Siauliai Mental Hospital, Lithuania; Jolanta Daiva Baliuniene, Klaipeda Mental Hospital, Klaipeda, Lithuania; Slawomir Dziadkiewicz, Wojewodzki Szpital Neuropsychiatryczny, Lubliniec, Poland; Marcin Olajossy, Klinika Psychiatrii, Lublin, Poland; Mieczyslaw Janiszewski, Wojewodzki Osrodek Leczenia Psychiatrycznego, Torun, Poland; Zbigniew Skurczynski, Wojewodzki Szpital Dla Nerwowo i Psychicznie, Zabki, Poland; Barbara Janczewska, Wojewodzki Szpital dla Nerwowo i Psychicznie, Swiecie, Poland; Krzysztof Wozniak, SP ZOZ w Ciborzu, Skape, Poland; Zbigniew Wawrzyniak, Szpital Specjalistyczny im. J. Babinskiego, Lodz, Poland; Leszek Bidzan, II Klinika Chorób Psychicznych AMG, Gdansk, Poland; Irina Dan, Spitalul Clinic de Psihiatrie, Bucharest, Romania; Liana Don, Clinical Psychiatric Hospital, Cluj, Romania; George Badescu, Spitalul Clinic de Neuropsihiatirie Craoiva, Dolj, Romania.