Predictors of psychiatric hospitalization during 6 months of maintenance treatment with olanzapine long-acting injection: post hoc analysis of a randomized, double-blind study

Haya Ascher-Svanum, Diego Novick, Josep Maria Haro, Jordan Bertsch, David McDonnell, Holland Detke, Haya Ascher-Svanum, Diego Novick, Josep Maria Haro, Jordan Bertsch, David McDonnell, Holland Detke

Abstract

Background: Hospitalization is a costly and distressing event associated with relapse during schizophrenia treatment. No information is available on the predictors of psychiatric hospitalization during maintenance treatment with olanzapine long-acting injection (olanzapine-LAI) or how the risk of hospitalization differs between olanzapine-LAI and oral olanzapine. This study aimed to identify the predictors of psychiatric hospitalization during maintenance treatment with olanzapine-LAI and assessed four parameters: hospitalization prevalence, incidence rate, duration, and the time to first hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of olanzapine-LAI and with oral olanzapine.

Methods: This was a post hoc exploratory analysis of data from a randomized, double-blind study comparing the safety and efficacy of olanzapine-LAI (pooled active depot groups: 405 mg/4 weeks, 300 mg/2 weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine-LAI (45 mg/4 weeks) during 6 months' maintenance treatment of clinically stable schizophrenia outpatients (n=1064). The four psychiatric hospitalization parameters were analyzed for each treatment group. Within the olanzapine-LAI group, patients with and without hospitalization were compared on baseline characteristics. Logistic regression and Cox's proportional hazards models were used to identify the best predictors of hospitalization. Comparisons between the treatment groups employed descriptive statistics, the Kaplan-Meier estimator and Cox's proportional hazards models.

Results: Psychiatric hospitalization was best predicted by suicide threats in the 12 months before baseline and by prior hospitalization. Compared with sub-therapeutic olanzapine-LAI, olanzapine-LAI was associated with a significantly lower hospitalization rate (5.2% versus 11.1%, p < 0.01), a lower mean number of hospitalizations (0.1 versus 0.2, p = 0.01), a shorter mean duration of hospitalization (1.5 days versus 2.9 days, p < 0.01), and a similar median time to first hospitalization (35 versus 60 days, p = 0.48). Olanzapine-LAI did not differ significantly from oral olanzapine on the studied hospitalization parameters.

Conclusions: In clinically stable schizophrenia outpatients receiving olanzapine-LAI maintenance treatment, psychiatric hospitalization was best predicted by a history of suicide threats and prior psychiatric hospitalization. Olanzapine-LAI was associated with a significantly lower incidence of psychiatric hospitalization and shorter duration of hospitalization compared with sub-therapeutic olanzapine-LAI. Olanzapine-LAI did not differ significantly from oral olanzapine on hospitalization parameters.

Trial registration: ClinicalTrials.gov: NCT00088491.

Figures

Figure 1
Figure 1
Time (days) to psychiatric hospitalization by treatment group: olanzapine-LAI, sub-therapeutic olanzapine-LAI, and oral olanzapine.

References

    1. Robinson D, Woerner MG, Alvir JM, Bilder R, Goldman R, Geisler S, Koreen A, Sheitman B, Chakos M, Mayerhoff D, Lieberman JA. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999;56:241–247. doi: 10.1001/archpsyc.56.3.241.
    1. Almond S, Knapp M, Francois C, Toumi M, Brugha T. Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatry. 2004;184:346–351. doi: 10.1192/bjp.184.4.346.
    1. Lieberman JA, Koreen AR, Chakos M, Sheitman B, Woerner M, Alvir JM, Bilder R. Factors influencing treatment response and outcome of first-episode schizophrenia: implications for understanding the pathophysiology of schizophrenia. J Clin Psychiatry. 1996;57(Suppl 9):5–9.
    1. Weiden PJ, Olfson M. Cost of relapse in schizophrenia. Schizophr Bull. 1995;21:419–429. doi: 10.1093/schbul/21.3.419.
    1. Wu EQ, Birnbaum HG, Shi L, Ball DE, Kessler RC, Moulis M, Aggarwal J. The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry. 2005;66:1122–1129. doi: 10.4088/JCP.v66n0906.
    1. Marcus SC, Olfson M. Outpatient antipsychotic treatment and inpatient costs of schizophrenia. Schizophr Bull. 2008;34:173–180.
    1. Peng X, Ascher-Svanum H, Faries D, Conley RR, Schuh KJ. Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia. Clinicoecon Outcomes Res. 2011;3:9–14.
    1. Gorwood P. Factors associated with hospitalisation of patients with schizophrenia in four European countries. Eur Psychiatry. 2011;26:224–230.
    1. Pompili M, Girardi P, Ruberto A, Tatarelli R. Toward a new prevention of suicide in schizophrenia. World J Biol Psychiatry. 2004;5:201–210. doi: 10.1080/15622970410029934.
    1. Roy A, Pompili M. Management of schizophrenia with suicide risk. Psychiatr Clin North Am. 2009;32:863–883. doi: 10.1016/j.psc.2009.08.005.
    1. Tiihonen J, Wahlbeck K, Lönnqvist J, Klaukka T, Ioannidis JPA, Volavka J, Haukka J. Effectiveness of antipsychotic treatments in a nation-wide cohort of 2230 patients in community care after the first hospitalization due to schizophrenia and schizoaffective disorder. Br Med J. 2006;333:224–227. doi: 10.1136/bmj.38881.382755.2F.
    1. Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168:603–609. doi: 10.1176/appi.ajp.2011.10081224.
    1. Barnes TR. Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. Psychopharmacol. 2011;25:567–620. doi: 10.1177/0269881110391123.
    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. doi: 10.1001/archpsyc.1979.01780120013001.
    1. Schooler NR, Keith SJ, Severe JB, Matthews SM, Bellack AS, Glick ID, Hargreaves WA, Kane JM, Ninan PT, Frances A, Jacobs M, Lieberman JA, Mance R, Simpson GM, Woerner MG. Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment. Arch Gen Psychiatry. 1997;54:453–463. doi: 10.1001/archpsyc.1997.01830170079011.
    1. Rauch AS, Fleischhacker WW. Long-acting injectable formulations of new-generation antipsychotics: a review from a clinical perspective. CNS Drugs. 2013. [Epub ahead of print]
    1. Law MR, Soumerai SB, Ross-Degnan D, Adams AS. A longitudinal study of medication nonadherence and hospitalization risk in schizophrenia. J Clin Psychiatry. 2008;69:47–53. doi: 10.4088/JCP.v69n0107.
    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. doi: 10.1016/j.schres.2010.11.020.
    1. Bitter I, Katona L, Zámbori J, Takács P, Fehér L, Diels J, Bacskai M, Lang Z, Gyáni G, Czobor P. Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary. Eur Neuropsychopharmacol. 2013. [Epub ahead of print]
    1. Kirson NY, Weiden PJ, Yermakov S, Huang W, Samuelson T, Offord SJ, Greenberg PE, Wong BJ. Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry. 2013;74:568–575. doi: 10.4088/JCP.12r08167.
    1. Lauriello J, Lambert T, Andersen S, Lin D, Taylor CC, McDonnell D. 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. doi: 10.4088/JCP.v69n0512.
    1. Kane JM, Detke HC, Naber D, Sethuraman G, Lin DY, Bergstrom RF, McDonnell D. 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. doi: 10.1176/appi.ajp.2009.07081221.
    1. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–276. doi: 10.1093/schbul/13.2.261.
    1. Guy W. ECDEU Assessment manual for psychopharmacology (revised) Rockville: National Institute of Mental Health; 1976. Clinical global impression; pp. 217–221.
    1. Liu-Seifert H, Ascher-Svanum H, Osuntokun O, Jen KY, Gomez JC. Change in level of productivity in the treatment of schizophrenia with olanzapine or other antipsychotics. BMC Psychiatry. 2011;11:87. doi: 10.1186/1471-244X-11-87.
    1. Hogan TP, Awad AG, Eastwood R. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol Med. 1983;13:177–183. doi: 10.1017/S0033291700050182.
    1. Ware J, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34:220–233. doi: 10.1097/00005650-199603000-00003.
    1. Barak Y, Baruch Y, Achiron A, Aizenberg D. Suicide attempts of schizophrenia patients: a case-controlled study in tertiary care. J Psychiatr Res. 2008;42:822–826. doi: 10.1016/j.jpsychires.2007.09.002.
    1. Doering S, Müller E, Köpcke W, Pietzcker A, Gaebel W, Linden M, Müller P, Müller-Spahn F, Tegeler J, Schüssler G. Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder. Schizophr Bull. 1988;24:87–98.
    1. Mortensen PB, Eaton WW. Predictors for readmission risk in schizophrenia. Psychol Med. 1994;24:223–232. doi: 10.1017/S0033291700026982.
    1. Ascher-Svanum H, Zhu B, Faries D, Salkever D, Slade E, Peng X, Conley RR. The cost of relapse and predictors of relapse in the treatment of schizophrenia. BMC Psychiatry. 2010;10:2. doi: 10.1186/1471-244X-10-2.
    1. Zeidler J, Slawik L, Fleischmann J, Greiner W. The costs of schizophrenia and predictors of hospitalisation from the statutory health insurance perspective. Health Econ Rev. 2012;2:9. doi: 10.1186/2191-1991-2-9.
    1. Gardner W, Lidz CW, Mulvey EP, Shaw EC. Clinical versus actuarial predictions of violence of patients with mental illnesses. J Consult Clin Psychol. 1996;64:602–609.
    1. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379(9831):2063–2071. doi: 10.1016/S0140-6736(12)60239-6.
    1. Novick D, Haro JM, Bertsch J, Anand H, Jemiai N, Haddad PM. Comparison of treatment discontinuation and hospitalization among nonadherent patients initiating depot or oral typical antipsychotic medications. Int Clin Psychopharmacol. 2012;27:275–282. doi: 10.1097/YIC.0b013e328354db12.

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