Dose trends for second-generation antipsychotic treatment of schizophrenia and bipolar disorder Leslie Citrome a,b, ⁎, Christopher Reist c , Liisa Palmer d , Leslie Montejano d , Greg Lenhart d , Brian Cuffel e , James Harnett e , Kafi N. Sanders e a Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA b New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA c University of California Irvine School of Medicine, 101 The City Drive South, Orange, CA 92868, USA d Thomson Reuters, 777 East Eisenhower Pkwy, Ann Arbor, MI 48108, USA e Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA article info abstract Article history: Received 26 September 2008 Received in revised form 13 November 2008 Accepted 17 November 2008 Available online 23 December 2008 Background: Antipsychotic dosing used in clinical practice can differ from dosing originally recommended in product labeling. This has been reported for olanzapine and quetiapine, where higher doses are commonly used. This may be the case for ziprasidone as well. Method: To characterize changes over time in dosing for the initial and subsequent prescriptions of first-line second-generation antipsychotics used during treatment episodes for outpatients with schizophrenia and bipolar disorder, the 2001–2005 Thomson MarketScan Medicaid Database (Medicaid) and the 2001–2006 MarketScan Commercial Claims and Encounters Database (Commercial) were analyzed. Dose trends were evaluated using autoregressive time-series models. Results: Data were available for 49180 treatment episodes of schizophrenia (4683 Commercial and 44 497 Medicaid) and 83 289 treatment episodes of bipolar disorder (57961 Commercial and 25 328 Medicaid). The initial prescription mean daily and overall mean daily doses of ziprasidone in schizophrenia episodes significantly increased across the Medicaid and Commercial populations, with similar trends observed for bipolar episodes. The first (May 2001) and last (December 2005) observed 3-month mean daily doses for ziprasidone were 112 mg/d and 138 mg/d for patients with schizophrenia and 93 mg/d and 113 mg/d for those with bipolar disorder in the Medicaid cohort, with similar findings for the Commercial cohort. Consistently significant trends in dose changes were not observed for the other medications, although quetiapine and olanzapine doses generally increased while aripiprazole and risperidone doses generally decreased. Conclusions: There remains a need for controlled randomized clinical trials that test fixed doses of antipsychotics to ascertain the dose–response relationship within the dose range used in contemporary clinical practice. © 2008 Elsevier B.V. All rights reserved. Keywords: Aripiprazole Dosing Olanzapine Quetiapine Risperidone Ziprasidone 1. Introduction When new medications become commercially available, clinicians rely on the dosing instructions contained in the product labeling. This has led to initial practices such as titrating risperidone from 2 mg/d to 6 mg/d by day 3, with subsequent increases to a maximum of 16 mg/d, or if prescribing quetiapine, going no higher than 500 mg/d (Citrome et al., 2005a). Ziprasidone, when launched for the Schizophrenia Research 108 (2009) 238–244 ⁎ Corresponding author. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962 USA. Tel.: +1 845 398 5595; fax: +1 845 398 5483. E-mail addresses: citrome@nki.rfmh.org (L. Citrome), creist@uci.edu (C. Reist), liisa.palmer@thomsonreuters.com (L. Palmer), leslie.montejano@thomsonreuters.com (L. Montejano), greg.lenhart@thomsonreuters.com (G. Lenhart), Brian.Cuffel@pfizer.com (B. Cuffel), James.Harnett@pfizer.com (J. Harnett), Kafi.Sanders@pfizer.com (K.N. Sanders). 0920-9964/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2008.11.017 Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres