Long-term safety and efficacy of olanzapine long-acting injection in patients with schizophrenia or schizoaffective disorder: a 6-year, multinational, single-arm, open-label study

David P McDonnell, John Landry, Holland C Detke, David P McDonnell, John Landry, Holland C Detke

Abstract

The objective of this study was to assess the long-term safety and efficacy of olanzapine long-acting injection (LAI). A 6-year, single-arm, open-label extension study of olanzapine LAI was conducted at 127 sites in 25 countries. Patients were 18-76 years of age, were diagnosed with schizophrenia or schizoaffective disorder (N=931), and had been previously enrolled in one of three clinical trials of olanzapine LAI. Patients received flexibly dosed (45-405 mg) olanzapine LAI every 2-4 weeks. The mean duration of exposure was ∼3 years. A total of 393 (42.2%) patients completed the study. The mean weight change was +2.1 kg (P<0.001), with 40.6% of patients experiencing 7% or higher weight gain. Treatment-emergent categorical changes occurred in fasting glucose, total cholesterol, and triglyceride levels. Pharmacokinetic analyses revealed no systemic accumulation of olanzapine after long-term treatment. There were 36 occurrences of post-injection delirium/sedation syndrome, all resolving within 72 h. The mean Positive and Negative Syndrome Scale total and subscale scores did not change significantly over the course of the study, indicating clinical stability. Olanzapine LAI appeared effective as a long-term maintenance treatment, with a safety profile generally consistent with the known profile of oral olanzapine, except for injection-related events (including post-injection delirium/sedation syndrome).

Trial registration: ClinicalTrials.gov NCT00088465.

Figures

Fig. 1
Fig. 1
Kaplan–Meier time to discontinuation.
Fig. 2
Fig. 2
Plasma olanzapine concentration versus time from first injection for year 1 through year 6. N, number of patients in the specified category; n, number of observations. The middle line in each box plot represents the median, the top and bottom margins of the box represent the 75th and 25th percentiles, the whiskers extend to the 95th and 5th percentiles, and data points outside the whiskers represent points beyond the 95th and 5th percentiles.
Fig. 3
Fig. 3
The Clinical Global Impression-Severity of Illness (CGI-S) visitwise mean score for all 931 patients enrolled in the olanzapine LAI open-label extension study (mean baseline=2.92, mean endpoint=2.74). LAI, long-acting injection.

References

    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders text revision 2000:4th ed.Washington, DC: American Psychiatric Association
    1. Ascher-Svanum H, Peng X, Montgomery W, Faries DE, Lawson AH, Witte MM, et al. Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia. Eur Psychiatry 2011; 26:313–319
    1. Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry 1989; 154:672–676
    1. Beasley CM, Jr, Sutton VK, Hamilton SH, Walker DJ, Dossenbach M, Taylor CC, et al. Olanzapine Relapse Prevention Study Group. A double-blind, randomized, placebo-controlled trial of olanzapine in the prevention of psychotic relapse. J Clin Psychopharmacol 2003; 23:582–594
    1. Bergstrom R, Callaghan J, Cerimele J, Kurtz D, Hatcher B.Tran P, Bymaster F, Tye N, Herra J, Breier A, Tollefson G. Population pharmacokinetics and plasma concentrations of olanzapine. Olanzapine (Zyprexa): a novel antipsychotic 2000Philadelphia: Lippincott, Williams, and Wilkins;232–252
    1. Bitter I, Treuer T, Dilbaz N, Oyffe I, Ciorabai EM, Gonzalez SL, et al. Patients’ preference for olanzapine orodispersible tablet compared with conventional oral tablet in a multinational, randomized, crossover study. World J Biol Psychiatry 2010; 11:894–903
    1. Citrome L, Stauffer VL, Chen L, Kinon BJ, Kurtz DL, Jacobson JG, et al. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/day in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol 2009; 29:278–283
    1. Detke HC, McDonnell DP, Brunner E, Zhao F, Sorsaburu S, Stefaniak VJ, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry 2010; 10:43.
    1. Detke HC, Weiden PJ, Llorca PM, Choukour M, Watson SB, Brunner E, Ascher-Svanum H. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia. J Clin Psychopharmacol 2014[Epub ahead of print]
    1. Gray R, Rofail D, Allen J, Newey T. A survey of patient satisfaction with and subjective experiences of treatment with antipsychotic medication. J Adv Nurs 2005; 52:31–37
    1. Gray R, Spilling R, Burgess D, Newey T. Antipsychotic long-acting injections in clinical practice: medication management and patient choice. Br J Psychiatry Suppl 2009; 195:S51–S56
    1. Guy W. ECDEU assessment manual for psychopharmacology, revised 1976Bethesda, MD: US Department of Health, Education and Welfare
    1. Hamann GL, Egan TM, Wells BG, Grimmig JE. Injection site reactions after intramuscular administration of haloperidol decanoate 100 mg/ml. J Clin Psychiatry 1990; 51:502–504
    1. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 2013; 14:2–44
    1. Hogarty GE, Schooler NR, Ulrich R, Mussare F, Ferro P, Herron E. Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. Arch Gen Psychiatry 1979; 36:1283–1294
    1. Jones JC, Day JC, Taylor JR, Thomas CS. Investigation of depot neuroleptic injection site reactions. Psychiatric Bull 1998; 22:605–607
    1. Kalali A. Patient satisfaction with, and acceptability of, atypical antipsychotics. Curr Med Res Opin 1999; 15:135–137
    1. Kane JM. Review of treatments that can ameliorate nonadherence in patients with schizophrenia. J Clin Psychiatry 2006; 67Suppl 59–14
    1. Kane JM, Detke HC, Naber D, Sethuraman G, Lin DY, Bergstrom RF, et al. Olanzapine long-acting injection: a 24-week, randomized, double-blind trial of maintenance treatment in patients with schizophrenia. Am J Psychiatry 2010; 167:181–189
    1. Kantrowitz JT, Citrome L. Olanzapine: review of safety 2008. Expert Opin Drug Saf 2008; 7:761–769
    1. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13:261–276
    1. Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, et al. Long-acting injectable vs. oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull 2014; 40:192–213
    1. Lambert T, Olivares JM, Peuskens J, Desouza C, Kozma CM, Otten P, et al. Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US Spain, Australia, and Belgium. Ann Gen Psychiatry 2011; 10:10.
    1. Lauriello J, Lambert T, Andersen S, Lin D, Taylor CC, McDonnell D, et al. An 8-week, double-blind, randomized, placebo-controlled study of olanzapine long-acting injection in acutely ill patients with schizophrenia. J Clin Psychiatry 2008; 69:790–799
    1. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophrenia – a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res 2011; 127:83–92
    1. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res 2005; 79:231–238
    1. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209–1223
    1. Macfadden W, Ma YW, Thomas Haskins J, Bossie CA, Alphs L. A prospective study comparing the long-term effectiveness of injectable risperidone long-acting therapy and oral aripiprazole in patients with schizophrenia. Psychiatry (Edgmont) 2010; 7:23–31
    1. McDonnell DP, Detke HC, Bergstrom RF, Kothare P, Johnson J, Stickelmeyer M, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry 2010; 10:45.
    1. Patel MX, Nikolaou V, David AS. Psychiatrists’ attitudes to maintenance medication for patients with schizophrenia. Psychol Med 2003; 33:83–89
    1. Pereira S, Pinto R. A survey of the attitudes of chronic psychiatric patients living in the community toward their medication. Acta Psychiatr Scand 1997; 95:464–468
    1. Perry PJ, Lund BC, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial. J Clin Psychopharmacol 2001; 21:14–20
    1. Robinson D, Woerner MG, Alvir JM, Bilder R, Goldman R, Geisler S, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1999; 56:241–247
    1. Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, et al. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med 2011; 364:842–851
    1. Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970; 212:11–19
    1. Thieda P, Beard S, Richter A, Kane J. An economic review of compliance with medication therapy in the treatment of schizophrenia. Psychiatr Serv 2003; 54:508–516
    1. Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv 2004; 55:886–891
    1. Wistedt B. How does the psychiatric patient feel about depot treatment, compulsion or help? Nord J Psychiatry 1995; 49Suppl 3541–46

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する