Effect of ziprasidone dose on all-cause discontinuation rates in acute schizophrenia and schizoaffective disorder: A post-hoc analysis of 4 fixed-dose randomized clinical trials Leslie Citrome a, ⁎, Ruoyong Yang b , Paul Glue c , Onur N. Karayal b a Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, and New York University School of Medicine, New York, United States b Pfizer Inc, New York, United States c University of Otago, Dunedin, New Zealand article info abstract Article history: Received 19 November 2008 Received in revised form 27 February 2009 Accepted 2 March 2009 Available online 17 April 2009 Background: Higher dose ziprasidone has been associated with improved treatment outcomes in patients with schizophrenia or schizoaffective disorder. This study examines the relationship of ziprasidone dose and all-cause discontinuation in randomized clinical trials in patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Method: Data were analyzed for the first 28 days from 4 pivotal, randomized, double-blind, fixed-dose ziprasidone trials. Patients in these trials had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder where ziprasidone was administered twice daily with food. Data were analyzed to examine the association between ziprasidone dose and all-cause discontinuation due to lack of efficacy, adverse events, or because of other reasons, relative to placebo. Differences in discontinuation were evaluated using Cox proportional hazard models and number needed to treat (NNT). Results: All-cause discontinuation for ziprasidone ranged from a low of 26.9% for the 160 mg/d dose group, to 40.9% for the 40 mg/d and 45.5% for the 80 mg/d groups, compared with 49.5% for placebo. The NNTs for avoiding 1 additional all-cause discontinuation compared with placebo were 12 (40 mg/d; n =186), 25 (80 mg/d; n =154), 9 (120 mg/d; n =125), and 4 (160 mg/d; n =104). The 120 mg/d and 160 mg/d groups were the only ziprasidone regimens associated with significantly lower all-cause discontinuation rates versus placebo in both the survival analysis (p = 0.031 and b 0.0001, respectively) and in examination of the NNT. The 160 mg/d group was associated with lower all-cause discontinuation rates versus lower-dose ziprasidone regimens (p =0.0158 for versus 40 mg/d, p = 0.002 for versus 80 mg/d). Efficacy accounted for 51% of all medication discontinuations across ziprasidone groups, compared with 62% for placebo. Findings for overall discontinuation due to lack of efficacy are consistent with results for all-cause discontinuation. Conclusions: Consistent with previous reports, higher doses of ziprasidone (120–160 mg/d, dosed twice daily with meals) are associated with significantly lower all-cause discontinuation rates and more favorable NNTs versus placebo. This was primarily driven by lower rates of discontinuation due to lack of efficacy. © 2009 Elsevier B.V. All rights reserved. Keywords: All-cause discontinuation Effectiveness Schizophrenia Randomized clinical trial Ziprasidone 1. Introduction Time to medication discontinuation is increasingly recog- nized as a clinically meaningful parameter of antipsychotic effectiveness in schizophrenia. Time to all-cause discontinua- tion is an integration of efficacy (improvement of symptoms), Schizophrenia Research 111 (2009) 39–45 ⁎ Corresponding author. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States. Tel.: +1 845 398 5595; fax: +1 845 398 5483. E-mail addresses: citrome@nki.rfmh.org (L. Citrome), Ruoyong.Yang@pfizer.com (R. Yang), paul.glue@otago.ac.nz (P. Glue), Onur.Karayal@pfizer.com (O.N. Karayal). 0920-9964/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2009.03.009 Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres