Predictors of Discontinuation of Antipsychotic Therapy in Patients with Acute Schizophrenia: A 1-Year Observational Study with More Than 1000 Patients
Affiliation(s)
1 Takahashi Psychiatric Clinic, Ashiya, Japan. 2 Statistical Science, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. 3 Science Communications, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. 4 Medical Science, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. 5 Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan.
1 Takahashi Psychiatric Clinic, Ashiya, Japan. 2 Statistical Science, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. 3 Science Communications, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. 4 Medical Science, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. 5 Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan.
ABSTRACT
Discontinuation of antipsychotic therapy has been a significant clinical issue among patients with schizophrenia, since the patients who discontinued antipsychotic treatment showed worse clinical and functional outcomes, and higher risks of relapse of schizophrenia symptoms and hospitalization. We conducted a post-hoc analysis of a post-marketing research with a 12-month follow-up period to identify the predictors for discontinuation of antipsychotic monotherapy in Japan. This is a prospective, naturalistic multicenter observational study, designed to evaluate the discontinuation rates of olanzapine monotherapy and non-olanzapine antipsychotic monotherapy in Japanese adult patients with acute schizophrenia. Patients were treatment-naive, or had switched from other antipsychotics or from poly-pharmacotherapy to oral antipsychotic monotherapy. We analyzed the correlation of discontinuation of antipsychotic monotherapy with baseline characteristics of patients. A total of 1089 patients (578 patients treated with olanzapine and 511 with non-olanzapine antipsychotics) were eligible for analysis. By the end of the 12-month study period, 614 patients (56.4%) discontinued antipsychotic therapy. Multivariate logistic regression analyses indicated significantly lower discontinuation rates in all patients treated with antipsychotics: older age (Odds ratio [OR], 0.871; 95% confidence interval [CI], 0.797 to 0.953; p = 0.003), outpatient status (OR, 0.508; 95% CI, 0.383 to 0.675; p < 0.001), prior use of antipsychotics (OR, 0.693; 95% CI, 0.516 to 0.930; p = 0.015), and olanzapine group showed lower discontinuation rate than that of non-olanzapine group (OR, 1.416; 95% CI, 1.086 to 1.846; p = 0.010). The present study indicated that the outpatient status, older age, and prior use of antipsychotics have better adherence to antipsychotic treatment. In addition to these factors, use of anti-parkinson agents showed lower discontinuation rates in the olanzapine monotherapy group.
Discontinuation of antipsychotic therapy has been a significant clinical issue among patients with schizophrenia, since the patients who discontinued antipsychotic treatment showed worse clinical and functional outcomes, and higher risks of relapse of schizophrenia symptoms and hospitalization. We conducted a post-hoc analysis of a post-marketing research with a 12-month follow-up period to identify the predictors for discontinuation of antipsychotic monotherapy in Japan. This is a prospective, naturalistic multicenter observational study, designed to evaluate the discontinuation rates of olanzapine monotherapy and non-olanzapine antipsychotic monotherapy in Japanese adult patients with acute schizophrenia. Patients were treatment-naive, or had switched from other antipsychotics or from poly-pharmacotherapy to oral antipsychotic monotherapy. We analyzed the correlation of discontinuation of antipsychotic monotherapy with baseline characteristics of patients. A total of 1089 patients (578 patients treated with olanzapine and 511 with non-olanzapine antipsychotics) were eligible for analysis. By the end of the 12-month study period, 614 patients (56.4%) discontinued antipsychotic therapy. Multivariate logistic regression analyses indicated significantly lower discontinuation rates in all patients treated with antipsychotics: older age (Odds ratio [OR], 0.871; 95% confidence interval [CI], 0.797 to 0.953; p = 0.003), outpatient status (OR, 0.508; 95% CI, 0.383 to 0.675; p < 0.001), prior use of antipsychotics (OR, 0.693; 95% CI, 0.516 to 0.930; p = 0.015), and olanzapine group showed lower discontinuation rate than that of non-olanzapine group (OR, 1.416; 95% CI, 1.086 to 1.846; p = 0.010). The present study indicated that the outpatient status, older age, and prior use of antipsychotics have better adherence to antipsychotic treatment. In addition to these factors, use of anti-parkinson agents showed lower discontinuation rates in the olanzapine monotherapy group.
KEYWORDS
Predictor of Discontinuation, Antipsychotic Monotherapy, Long-Term Observational Study, Schizophrenia
Predictor of Discontinuation, Antipsychotic Monotherapy, Long-Term Observational Study, Schizophrenia
Cite this paper
Takahashi, M. , Fujikoshi, S. , Funai, J. , Alev, L. and Iyo, M. (2014) Predictors of Discontinuation of Antipsychotic Therapy in Patients with Acute Schizophrenia: A 1-Year Observational Study with More Than 1000 Patients. Open Journal of Psychiatry, 4, 364-371. doi: 10.4236/ojpsych.2014.44042.
Takahashi, M. , Fujikoshi, S. , Funai, J. , Alev, L. and Iyo, M. (2014) Predictors of Discontinuation of Antipsychotic Therapy in Patients with Acute Schizophrenia: A 1-Year Observational Study with More Than 1000 Patients. Open Journal of Psychiatry, 4, 364-371. doi: 10.4236/ojpsych.2014.44042.
References
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http://dx.doi.org/10.1016/j.comppsych.2010.12.003 [5] Tunis, S.L., Faries, D.E., Nyhuis, A.W., Kinon, B.J., Ascher-Svanum, H. and Aquila, R. (2006) Cost-Effectiveness of Olanzapine as First-Line Treatment for Schizophrenia: Results from a Randomized, Open-Label, 1-Year Trial. Value Health, 9, 77-89.
http://dx.doi.org/10.1111/j.1524-4733.2006.00083.x [6] Hodgson, R., Belgamwar, R., Al-Tawarah, Y. and MacKenzie, G. (2005) The Use of Atypical Antipsychotics in the Treatment of Schizophrenia in North Staffordshire. Human Psychopharmacology, 20, 141-147. [7] Jung, S.H., Kim, W.H., Choi, H.J., Kang, M.H., Lee, J.S., Bae, J.N. and Kim, C.E. (2011) Factors Affecting Treatment Discontinuation and Treatment Outcome in Patients with Schizophrenia in Korea: 10-Year Follow-Up Study. Psychiatry Investigation, 8, 22-29. http://dx.doi.org/10.4306/pi.2011.8.1.22 [8] Mullins, C.D., Obeidat, N.A., Cuffel, B.J., Naradzay, J. and Loebel, A.D. (2008) Risk of Discontinuation of Atypical Antipsychotic Agents in the Treatment of Schizophrenia. Schizophrenia Research, 98, 8-15. http://dx.doi.org/10.1016/j.schres.2007.04.035 [9] Gaebel, W., Riesbeck, M., von Wilmsdorff, M., Burns, T., Derks, E.M., Kahn, R.S., Rossler, W. and Fleischhacker, W.W., for the EUFEST Study Group (2010) Drug Attitude as Predictor for Effectiveness in First-Episode Schizophrenia: Results of an Open Randomized Trial (EUFEST). European Neuropsychopharmacology, 20, 310-316. http://dx.doi.org/10.1016/j.euroneuro.2010.02.001 [10] Gianfrancesco, F., Rajagopalan, K., Sajatovic, M. and Wang, R.H. (2006) Treatment Adherence among Patients with Schizophrenia Treated with Atypical and Typical Antipsychotics. Psychiatry Research, 144, 177-189. http://dx.doi.org/10.1016/j.psychres.2006.02.006 [11] Kreyenbuhl, J., Slade, E.P., Medoff, D.R., Brown, C.H., Ehrenreich, B., Afful, J. and Dixon, L.B. (2011) Time to Discontinuation of First- and Second-Generation Antipsychotic Medications in the Treatment of Schizophrenia. Schizophrenia Research, 131, 127-132.
http://dx.doi.org/10.1016/j.schres.2011.04.028 [12] Ye, W., Ascher-Svanum, H., Tanji, Y., Flynn, J.A. and Takahashi, M. (2011) Predictors of Continuation with Olanzapine during the 1-Year Naturalistic Treatment of Patients with Schizophrenia in Japan. Patient Prefer Adherence, 5, 611-617. http://dx.doi.org/10.2147/PPA.S26002 [13] Takahashi, M., Fujikoshi, S., Nakahara, N. and Iyo, M. (2013) The Continuation Rate of Monotherapy with Olanzapine or Other Antipsychotic Drugs in Patients with Acute-Phase Schizophrenia—A 1-Year Observational Study in Routine Clinical Practice. Japanese Journal of Clinical Psychopharmacology, 16, 1649-1660. [14] San, L., Arranz, B., Perez, V., Safont, G., Corripio, I., Ramirez, N., Duenas, R. and Alvarez, E. (2012) One-Year, Randomized, Open Trial Comparing Olanzapine, Quetiapine, Risperidone and Ziprasidone Effectiveness in Antipsychotic-Naive Patients with a First-Episode Psychosis. Psychiatry Research, 200, 693-701. http://dx.doi.org/10.1016/j.psychres.2012.07.005 [15] Beasley Jr., C.M., Stauffer, V.L., Liu-Seifert, H., Taylor, C.C., Dunayevich, E. and Davis, J.M. (2007) All-Cause Treatment Discontinuation in Schizophrenia during Treatment with Olanzapine Relative to Other Antipsychotics: An Integrated Analysis. Journal of Clinical Psychopharmacology, 27, 252-258.
[1] American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th Edition, American Psychiatric Publishing, Arlington. [2] Davis, S.M., Stroup, T.S., Koch, G.G., Davis, C.E., Rosenheck, R.A. and Lieberman, J.A. (2011) Time to All-Cause Treatment Discontinuation as the Primary Outcome in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Study. Statistics in Biopharmaceutical Research, 3, 253-265. http://dx.doi.org/10.1198/sbr.2011.10013 [3] Lieberman, J.A., Stroup, T.S., McEvoy, J.P., Swartz, M.S., Rosenheck, R.A., Perkins, D.O., Keefe, R.S., Davis, S.M., Davis, C.E., Lebowitz, B.D., Severe, J. and Hsiao, J.K., for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators (2005) Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. The New England Journal of Medicine, 353, 1209-1223. http://www.nejm.org/doi/full/10.1056/NEJMoa051688 [4] Liu-Seifert, H., Osuntokun, O.O. and Feldman, P.D. (2012) Factors Associated with Adherence to Treatment with Olanzapine and Other Atypical Antipsychotic Medications in Patients with Schizophrenia. Comprehensive Psychiatry, 53, 107-115.
http://dx.doi.org/10.1016/j.comppsych.2010.12.003 [5] Tunis, S.L., Faries, D.E., Nyhuis, A.W., Kinon, B.J., Ascher-Svanum, H. and Aquila, R. (2006) Cost-Effectiveness of Olanzapine as First-Line Treatment for Schizophrenia: Results from a Randomized, Open-Label, 1-Year Trial. Value Health, 9, 77-89.
http://dx.doi.org/10.1111/j.1524-4733.2006.00083.x [6] Hodgson, R., Belgamwar, R., Al-Tawarah, Y. and MacKenzie, G. (2005) The Use of Atypical Antipsychotics in the Treatment of Schizophrenia in North Staffordshire. Human Psychopharmacology, 20, 141-147. [7] Jung, S.H., Kim, W.H., Choi, H.J., Kang, M.H., Lee, J.S., Bae, J.N. and Kim, C.E. (2011) Factors Affecting Treatment Discontinuation and Treatment Outcome in Patients with Schizophrenia in Korea: 10-Year Follow-Up Study. Psychiatry Investigation, 8, 22-29. http://dx.doi.org/10.4306/pi.2011.8.1.22 [8] Mullins, C.D., Obeidat, N.A., Cuffel, B.J., Naradzay, J. and Loebel, A.D. (2008) Risk of Discontinuation of Atypical Antipsychotic Agents in the Treatment of Schizophrenia. Schizophrenia Research, 98, 8-15. http://dx.doi.org/10.1016/j.schres.2007.04.035 [9] Gaebel, W., Riesbeck, M., von Wilmsdorff, M., Burns, T., Derks, E.M., Kahn, R.S., Rossler, W. and Fleischhacker, W.W., for the EUFEST Study Group (2010) Drug Attitude as Predictor for Effectiveness in First-Episode Schizophrenia: Results of an Open Randomized Trial (EUFEST). European Neuropsychopharmacology, 20, 310-316. http://dx.doi.org/10.1016/j.euroneuro.2010.02.001 [10] Gianfrancesco, F., Rajagopalan, K., Sajatovic, M. and Wang, R.H. (2006) Treatment Adherence among Patients with Schizophrenia Treated with Atypical and Typical Antipsychotics. Psychiatry Research, 144, 177-189. http://dx.doi.org/10.1016/j.psychres.2006.02.006 [11] Kreyenbuhl, J., Slade, E.P., Medoff, D.R., Brown, C.H., Ehrenreich, B., Afful, J. and Dixon, L.B. (2011) Time to Discontinuation of First- and Second-Generation Antipsychotic Medications in the Treatment of Schizophrenia. Schizophrenia Research, 131, 127-132.
http://dx.doi.org/10.1016/j.schres.2011.04.028 [12] Ye, W., Ascher-Svanum, H., Tanji, Y., Flynn, J.A. and Takahashi, M. (2011) Predictors of Continuation with Olanzapine during the 1-Year Naturalistic Treatment of Patients with Schizophrenia in Japan. Patient Prefer Adherence, 5, 611-617. http://dx.doi.org/10.2147/PPA.S26002 [13] Takahashi, M., Fujikoshi, S., Nakahara, N. and Iyo, M. (2013) The Continuation Rate of Monotherapy with Olanzapine or Other Antipsychotic Drugs in Patients with Acute-Phase Schizophrenia—A 1-Year Observational Study in Routine Clinical Practice. Japanese Journal of Clinical Psychopharmacology, 16, 1649-1660. [14] San, L., Arranz, B., Perez, V., Safont, G., Corripio, I., Ramirez, N., Duenas, R. and Alvarez, E. (2012) One-Year, Randomized, Open Trial Comparing Olanzapine, Quetiapine, Risperidone and Ziprasidone Effectiveness in Antipsychotic-Naive Patients with a First-Episode Psychosis. Psychiatry Research, 200, 693-701. http://dx.doi.org/10.1016/j.psychres.2012.07.005 [15] Beasley Jr., C.M., Stauffer, V.L., Liu-Seifert, H., Taylor, C.C., Dunayevich, E. and Davis, J.M. (2007) All-Cause Treatment Discontinuation in Schizophrenia during Treatment with Olanzapine Relative to Other Antipsychotics: An Integrated Analysis. Journal of Clinical Psychopharmacology, 27, 252-258.