Effectiveness and Cost of Atypical Versus Typical Antipsychotic Treatment in a Nationwide Cohort of Patients With Schizophrenia in Germany Tom Stargardt, PhD,* Marc-Andreas Edel, MD,*Þ Andreas Ebert, MD,Þ Reinhard Busse, MD, PhD, MPH, FFPH,þ Georg Juckel, MD, PhD,Þ and Christian A. Gericke, MD, PhD, MPH,MSc, FRCP, FACP§ Abstract: This study investigates the effectiveness and cost of typical versus atypical antipsychotics in a nationwide German cohort of pa- tients with schizophrenia. The study sample consisted of patients insured with 4 sickness funds (n = 8,610) who were followed up for 12 months after hospital discharge with a diagnosis of schizophrenia in 2003. Multivariate regression models were fitted to assess the relationship be- tween outcome variables (rehospitalization, bed-days, prescriptions against adverse effects, cost) and medication type, sex, age, and severity. Sever- ity was assessed by prior bed-days due to schizophrenia during 2000 to 2002. Risk of rehospitalization did not differ between groups but within each group severity (P = 0.0003). Males (P = 0.0016) and patients younger than 35 years (P G 0.0001) had a higher risk of rehospitaliza- tion. Number of bed-days was lower for treatment with typicals compared with atypicals (P G 0.0001); furthermore, bed-days depended on severity of disease (P G 0.0001). Prescriptions of drugs against extrapyramidal symptoms, anxiety, and agitation were higher for patients treated with typicals (P G 0.0001 for each). Mean predicted treatment cost per year was €6442 for atypicals versus €4443 for typicals (P G 0.0001). This study does not support unconditional superiority of atypicals over typ- icals, neither in terms of effectiveness nor in terms of cost. Key Words: typical antipsychotic treatment, atypical antipsychotic treatment, schizophrenia, cost and effectiveness, Germany (J Clin Psychopharmacol 2012;32: 602Y607) S chizophrenia is a chronic disease with a lifetime prevalence of approximately 4 in 1000 and an annual incidence of 20 to 22 cases per 100,000. 1,2 The disorder affects a broad range of emotional, cognitive, and social functions including regula- tion of feelings, perception, attention, thinking, motivation, self- care, and social interaction. Core features are formal thought disorder, delusional beliefs, and hallucinations. After onset, about 20% of afflicted individuals fully recover, 70% suffer from re- peated psychotic episodes, and 10% remain continuously af- fected, being unable to work. Early onset, which usually occurs in the 20s or 30s, results in temporary or permanent impairment with high economic losses to individuals and families and high private and public expenditure for health care and social ser- vices. 2 In the Global Burden of Disease Study, the World Health Organization ranked schizophrenia in fifth place, accounting for 1.15% of the total burden of disease as measured in disability- adjusted life-years in Western Europe. 3 In at least one third of cases, schizophrenia develops a chronic course. Because every schizophrenic episode worsens long-term prognosis, prevention of relapse represents a major therapeutic goal. One of the main reasons for psychotic exac- erbation is noncompliance with antipsychotic treatment, which is often due to the intolerable adverse effects of antipsychotic agents. The particular causes of patients discontinuing antipsy- chotic treatment are extrapyramidal symptoms (EPSs) in all their forms, as well as aggravation of negative symptoms, both of which are common adverse effects of typical antipsychotic drugs. Since the launch of the first atypical antipsychotic, cloza- pine, in 1973, it has been argued that atypical antipsychotic drugs are superior to typical antipsychotic drugs, in regard both to their efficacy and their adverse effect profile. 4 This may, in turn, lead to higher acceptance by patients and thus improved therapy adherence as well as reduced hospital stays. 5,6 However, a number of studies have questioned this as- sumption, with doubts arising in particular from those studies performed under routine clinical conditions. 7Y9 In one such critically study, no significant differences in effectiveness were found between atypical and typical antipsychotic drugs within a small sample of members of 1 German sickness fund. Moreover, it was only in the subgroup of the most severely afflicted pa- tients that the higher cost of atypical antipsychotics was com- pensated for by a reduction of inpatient time. 9 To test these findingsVeither by replicating them or in- validating themVwe analyzed the effectiveness of atypical versus typical antipsychotic drug treatment within a larger and more representative sample using routine data from 4 Ger- man sickness funds. With a total of 12.6 million insurees, these 4 funds together cover 17.9% of those persons covered by the Statutory Health Insurance system or 15% of the German population. ORIGINAL CONTRIBUTION 602 www.psychopharmacology.com Journal of Clinical Psychopharmacology & Volume 32, Number 5, October 2012 From the *Hamburg Center for Health Economics, University of Hamburg, Hamburg; †Department of Psychiatry, Ruhr University Bochum, LWL Uni- versity Hospital Bochum; ‡Department of Health Care Management, World Health Organization Collaborating Centre for Health Systems Research and Management, Berlin University of Technology, Berlin, Germany; and §Pen- insula CLAHRC, National Institute for Health Research, Peninsula Medical School, Universities of Exeter & Plymouth, Plymouth, UK. Received February 21, 2011; accepted after revision March 12, 2012. Reprints: Tom Stargardt, PhD, Hamburg Center for Health Economics, University of Hamburg, Esplanade 36, 20354 Hamburg, Germany (e-mail: Tom.Stargardt@wiso.uni-hamburg.de). This study was supported by an investigator-initiated research grant from Janssen Cilag, Neuss, Germany, a manufacturer of atypical and typical antipsychotics. The sponsor had no role in the study design, collection and analysis of data, the writing of the report, or the submission of the paper for publication. Financial support for CAG’s contribution by the National Institute for Health Research (NIHR) is gratefully acknowledged. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health in England. Drs Stargardt and Edel have contributed equally to this work. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.psychopharmacology.com). Copyright * 2012 by Lippincott Williams & Wilkins ISSN: 0271-0749 DOI: 10.1097/JCP.0b013e318268ddc0 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.