Original Article| Volume 62, ISSUE 12, P1363-1370, December 15, 2007

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Efficacy and Safety of Paliperidone Extended-Release Tablets: Results of a 6-Week, Randomized, Placebo-Controlled Study


      Paliperidone extended-release tablet (paliperidone ER; Invega, Janssen L.P., Titusville, New Jersey) is an oral psychotropic for schizophrenia treatment.


      Efficacy and safety of once-daily paliperidone ER (6 and 12 mg) were assessed versus placebo in 444 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An olanzapine (10 mg) treatment arm was included to confirm trial validity.


      Both doses of paliperidone ER demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total score (p ≤ .006) and certain PANSS Marder factor scores compared with placebo (p ≤ .025); PANSS total score also improved in the olanzapine treatment arm. Paliperidone ER 6 mg (p ≤ .008), but not 12 mg, was associated with significant improvements in personal and social performance. The incidence of treatment-emergent adverse events (AEs) for paliperidone ER 6 mg was comparable with placebo and slightly greater with paliperidone ER 12 mg. Changes in blood glucose and lipid levels with paliperidone ER were comparable with placebo. Two patients treated with paliperidone ER experienced glucose-related AEs. Body-weight increases of 1-2 kg were observed with paliperidone ER. Although there were increases in plasma prolactin levels with paliperidone ER treatment, the incidence of prolactin-related AEs was ≤1%.


      In this study, paliperidone ER, particularly the 6-mg dose, was effective and well tolerated, and provides a valuable new treatment option for schizophrenia.

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        • Keith S.J.
        • Kane J.M.
        Partial compliance and patient consequences in schizophrenia: Our patients can do better.
        J Clin Psychiatry. 2003; 64: 1308-1315
        • Lieberman J.A.
        • Stroup T.S.
        • McEvoy J.P.
        • Swartz M.S.
        • Rosenheck R.A.
        • Perkins D.O.
        • et al.
        Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
        N Engl J Med. 2005; 353: 1209-1223
        • Masand P.S.
        • Berry S.L.
        Switching antipsychotic therapies.
        Ann Pharmacother. 2000; 34: 200-207
        • Nasrallah H.A.
        • Targum S.D.
        • Tandon R.
        • McCombs J.S.
        • Ross R.
        Defining and measuring clinical effectiveness in the treatment of schizophrenia.
        Psychiatr Serv. 2005; 56: 273-282
        • Karow A.
        • Naber D.
        Subjective well-being and quality of life under atypical antipsychotic treatment.
        Psychopharmacology (Berl). 2002; 162: 3-10
        • Saleem P.
        • Olie J.P.
        • Loo H.
        Social functioning and quality of life in the schizophrenic patient: Advantages of amisulpride.
        Int Clin Psychopharmacol. 2002; 17: 1-8
        • Morosini P.L.
        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
        • Gagnon D.
        • Adriaenssen I.
        • Nasrallah H.
        • Morosini P.
        Reliability, validity and sensitivity to change of the personal and social performance scale in patients with stable schizophrenia.
        Int J Neuropsychopharmacol. 2006; 9: 288
        • Patrick D.
        • Adriaenssen I.
        • Morosini P.
        • Rothman M.
        Reliability, validity and sensitivity to change of the personal and social performance scale in patients with acute schizophrenia.
        Int J Neuropsychopharmacol. 2006; 9: S287-S288
        • Ceskova E.
        • Svestka J.
        Double-blind comparison of risperidone and haloperidol in schizophrenic and schizoaffective psychoses.
        Pharmacopsychiatry. 1993; 26: 121-124
        • Lindstrom E.
        • Eriksson B.
        • Hellgren A.
        • von Knorring L.
        • Eberhard G.
        Efficacy and safety of risperidone in the long-term treatment of patients with schizophrenia.
        Clin Ther. 1997; 17: 402-412
        • Moller H.
        • Gagiano C.
        • Addington D.
        • Von Knorring L.
        • Torres-Plank J.
        • Gaussares C.
        Long-term treatment of chronic schizophrenia with risperidone: An open-label, multicenter study of 386 patients.
        Int Clin Psychopharmacol. 1998; 13: 99-106
        • Peuskens J.
        • Group R.S.
        Risperidone in the treatment of patients with chronic schizophrenia: A multi-national, multi-centre, double-blind, parallel-group study versus haloperidol.
        Br J Psychiatry. 1995; 166: 712-716
        • Conley R.
        • Gupta S.
        • Sathyan G.
        Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form.
        Curr Med Res Opin. 2006; 22: 1879-1892
        • Karlsson P.
        • Dencker E.
        • Nyberg S.
        • Cselenyi Z.
        • Mannaert E.
        • Boom S.
        • et al.
        Pharmacokinetics, dopamine D2 and serotonin 5-HT2A receptor occupancy and safety profile of paliperidone extended-release in healthy subjects.
        Clin Pharmacol Ther. 2006; 79: P111-P157
        • Vermeir M.
        • Boom S.
        • Naessens I.
        • Talluri K.
        • Eerdekens M.
        Absorption, metabolism and excretion of a single oral dose of 14C-paliperidone 1 mg in healthy subjects.
        Eur Neuropsychopharmacol. 2005; 30: S191-S192
        • Kay S.
        • Opler L.
        • Fizbein A.
        The positive and negative syndrome scale (PANSS) manual.
        Multi-Health System, North Tohawanda, NY1986
        • 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
        • Guy W.
        Clinical Global Impressions Scale.
        ECDEU Assessment manual. 1976; : 218-222
        • Malik M.
        • Camm A.
        Evaluation of drug-induced QT interval prolongation: Implications for drug approval and labelling.
        Drug Saf. 2001; 24: 323-351
        • Hodges M.
        Rate correction of the QT interval.
        Cardiac Electrophysiol Rev. 1997; 1: 360-363
        • Welge J.
        • Keck P.
        Moderators of placebo response to antipsychotic treatment in patients with schizophrenia: A meta-regression.
        Psychopharmacology. 2003; 166: 1-10
        • Kane J.
        • Canas F.
        • Kramer M.
        • Ford L.
        • Gassman-Mayer C.
        • Lim P.
        • et al.
        Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial.
        Schizophr Res. 2007; 90: 147-161
        • Wahlbeck K.
        • Tuunainen A.
        • Ahokas A.
        • Leucht S.
        Dropout rates in randomised antipsychotic drug trials.
        Psychopharmacology (Berl). 2001; 155: 230-233
        • Storosum J.
        • Elferink A.
        • van Zwieten B.
        Schizophrenia: Do we really need placebo-controlled studies?.
        Eur Neuropsychopharmacol. 1998; 8: 279-286
        • Citrome L.L.
        The increase in risk of diabetes mellitus from exposure to second-generation antipsychotic agents.
        Drugs Today (Barc). 2004; 40: 445-464
        • American Psychiatric Association and American Diabetic Association
        Consensus development conference on antipsychotic drugs and obesity and diabetes.
        J Clin Psychiatry. 2004; 65: 267-272
        • Sernyak M.J.
        • Leslie D.L.
        • Alarcon R.D.
        • Losonczy M.F.
        • Rosenheck R.
        Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia.
        Am J Psychiatry. 2002; 159: 561-566
        • Karlsson P.
        • Dencker D.
        • Nyberg S.
        • Mannaert E.
        • Boom S.
        • Talluri K.
        • et al.
        Pharmacokinetics and dopamine d2 and serotonin 5-HT2A receptor occupancy of paliperidone in healthy subjects.
        Eur Neuropsychopharmacol. 2005; 15: 385
        • Bhana N.
        • Foster R.
        • Olney R.
        • Plosker G.
        Olanzapine: An updated review of its use in the management of schizophrenia.
        Drugs. 2001; 61: 111-161
        • Ereshefsky L.
        • Mascarenas C.A.
        Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics.
        J Clin Psychiatry. 2003; 64: 18-23
        • 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
        • Kramer M.
        • Kushner S.
        • Vijapurkar U.
        • Lim P.
        • Eerdekens M.
        Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: A randomized, double-blind, placebo-controlled study.
        J Clin Psychopharmacol. 2007; 27: 6-14
        • Davidson M.
        • Emsley R.
        • Kramer M.
        • Ford L.
        • Gassmann-Mayer C.
        • Lim P.
        • et al.
        Efficacy and safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study.
        Schizophr Res. 2007; (Apr 26; Epub ahead of print; doi:10.1016/j.schres.2007.03.003)