Antipsychotic Medications: Prevalence of Inappropriate Use, Polypharmacy, and Non-Adherence Nancy G. Pham, PharmD; Lisa Le, MS; Karen M. Stockl, PharmD; Jennifer S. Shin, PharmD; Brian K. Solow, MD, FAAFP; Bradford S. Curtis, MD, FAAP; Heidi C. Lew, PharmD Prescription Solutions, Irvine, CA Objective Conclusion Results showed a low prevalence of antipsychotic medication polypharmacy and a high prevalence of antipsychotic medication non-adherence and inappropriate use among the populations examined in this study. These findings suggest proactive monitoring and clinical intervention programs are necessary to improve antipsychotic medication adherence and appropriate use. Presented at the Academy Managed Care Pharmacy 22 nd Annual Meeting and Showcase, San Diego, California – April 7-10, For more information, please contact Nancy Pham via telephone: (949) or © 2010 Prescription Solutions. This document is proprietary to Prescription Solutions and is subject to federal copyright protection. Any reproduction, dissemination or use of this document without the express prior written consent of Prescription Solutions is strictly prohibited. Background Results Between 1996 and 2005, antipsychotic users have increased from 0.72% to 1.17% in the United States. 1 This growth in utilization has generated interest among managed care organizations to examine the reasons for this trend and identify ways to ensure the appropriate use of antipsychotic medications. Some of the leading concerns surrounding antipsychotic medication use include polypharmacy (concurrently on ≥ 2 antipsychotic agents), medication non-adherence and inappropriate use (which includes off- label indications, off-label dosing, and drug-disease interactions). Table 1. Baseline Characteristics Figure 1. Prevalence of Antipsychotic Medication Non-Adherence Commercial (N = 7,310 ) PDP (N = 153,500) MAPD (N = 21,711) Medicaid (N = 8,109) Age, mean (SD)37.6 (19.9)60.9 (18.3)68.6 (16.9)27.1 (16.5) Chronic disease score 2, mean (SD) 2.74 (2.7)4.57 (3.3)4.42 (3.3)2.44 (2.6) Female gender, n (%) 3,830 (52.4)90,831 (59.2)14,078 (64.8)3,988 (49.2) Patients with atypical antipsychotic, n (%) Aripiprazole Paliperidone Risperidone Ziprasidone Patients with conventional antipsychotic, n (%) Chlorpromazine Fluphenazine Haloperidol Loxapine Molindone Perphenazine Pimozide Thiothixene Thioridazine Trifluoperazine 2,959 (40.5) 206 (2.8) 3,064 (41.9) 955 (13.1) 217 (3.0) 37 (0.5) 321 (4.4) 22 (0.3) 2 (0.03) 104 (1.4) 40 (0.6) 42 (0.6) 66 (0.9) 59 (0.8) 38,031 (24.8) 6,388 (4.2) 72,907 (47.5) 17,976 (11.7) 5,498 (3.6) 4,202 (2.7) 20,102 (13.1) 1,423 (0.9) 331 (0.2) 4,251 (2.8) 263 (0.2) 2,648 (1.7) 3,037 (2.0) 2,313 (1.5) 3,916 (18.0) 535 (2.5) 10,784 (49.7) 1,861 (8.6) 901 (4.1) 476 (2.2) 3,458 (15.9) 209 (1.0) 23 (0.1) 681 (3.1) 37 (0.2) 426 (2.0) 458 (2.1) 421 (1.9) 3,295 (40.6) 104 (1.3) 3,462 (42.6) 1,182 (14.6) 156 (1.9) 104 (1.3) 355 (4.4) 24 (0.3) 11 (0.1) 202 (2.5) 16 (0.2) 67 (0.8) 69 (0.9) 51 (0.6) Figure 5. Prevalence of Drug-Disease Interactions Among Patients Using Specific Antipsychotic Medications (Medical Data Subgroup) Figure 3. Distribution of Approved and Off-Label Use among Commercial Patients with Medical Claims Data Study Design Cross-sectional analysis Electronic pharmacy and medical claims from multiple health insurance plans across the United States with Commercial, PDP, MAPD, and Medicaid members Inclusion criteria Identification period – Jan. 1, 2008 through Dec. 31, 2008 Antipsychotic prescription during the identification period Continuously enrolled during the identification period Cohort selection Identified patients were stratified according to health plan type (Commercial, PDP, MAPD, Medicaid) Primary outcome Prevalence of polypharmacy - possession of two or more chemically distinct antipsychotics with an overlapping days supply of at least 45 days Prevalence of non-adherence - medication possession ratio (MPR) of less than 80% or a gap in therapy >7 days from the expected fill date Prevalence of inappropriate use Off-label dosing – daily dosing above maximum recommended dose or below minimum recommended dose Off-label use (among subgroup with medical data) – no medical claims history of an FDA-approved use Drug-disease interactions (among the subgroup with medical data) Use of thioridazine and/or ziprasidone with a history of heart failure or myocardial infarction (MI) Use of haloperidol, risperidone, olanzapine, perphenazine, thioridazine, chlorpromazine, fluphenazine, trifluoperazine, loxapine, molindone, and/or thiothixene with a history of osteoporosis or osteopenia Use of pimozide, haloperidol, thioridazine and/or ziprasidone with a history of cardiac arrhythmia Methods To measure the prevalence of polypharmacy, non-adherence, and inappropriate use of antipsychotics within Commercial, Medicare Part D Prescription Drug Plan (PDP), Medicare Advantage Prescription Drug (MAPD), and Medicaid populations Commercial (N =2,891 ) MAPD (N = 20,125) Age, mean (SD)34.6 (18.3)68.8 (17.0) Chronic disease score 2, mean (SD)2.52 (2.5)4.44 (3.3) Female gender, n (%)1,464 (50.6)13,111 (65.2) Patients with atypical antipsychotic, n (%) Aripiprazole Paliperidone Risperidone Ziprasidone Patients with conventional antipsychotic, n (%) Chlorpromazine Fluphenazine Haloperidol Loxapine Molindone Perphenazine Pimozide Thiothixene Thioridazine Trifluoperazine 1,174 (40.6) 94 (3.3) 1,245 (43.1) 368 (12.7) 85 (2.9) 11 (0.4) 110 (3.8) 8 (0.3) 1 (0.03) 32 (1.1) 14 (0.5) 15 (0.5) 20 (0.7) 25 (0.9) 3,613 (18.0) 487 (2.4) 10,135 (50.4) 1,723 (8.6) 801 (4.0) 427 (2.1) 3,179 (15.8) 203 (1.0) 18 (0.1) 617 (3.1) 36 (0.2) 391 (1.9) 421 (2.1) 373 (1.9) Table 2. Baseline Characteristics for a Sub-Analysis of Patients with Medical Claims Figure 4. Distribution of Approved and Off-Label Use among MAPD Patients with Medical Claims Data Figure 2. Prevalence of Antipsychotic Medication Off-Label Dosing (First Prescription Fill During Identification Period) Discussion The percentage of patients with antipsychotic medication polypharmacy was low (<7%) across all plans. Non-adherence to the treatment with antipsychotics was high across all plans. The percentage of patients with an MPR 7 days ranged between 71% and 92%. On the first prescription fill, the prevalence of prescribing doses below the minimum recommended dose ranged between 7% and 40%, while the prevalence of prescribing doses above the maximum recommended dose was low (<3%). Approximately 77% of antipsychotic users in the MAPD plan and 44% of antipsychotic users in the Commercial plan did not have an FDA approved indication for antipsychotics, signifying a high prevalence of off-label use. Between 2% to 5% of the patients with thioridazine and/or ziprasidone, which may worsen heart failure or increase the risk of MI, were found with a history of heart failure or MI. A range of 4% to 13% of patients with haloperidol, risperidone, olanzapine, perphenazine, thioridazine, chlorpromazine, fluphenazine, trifluoperazine, loxapine, molindone, and/or thiothixene, which may increase the risk bone fractures, were found with a history of osteoporosis or osteopenia. Furthermore, between 11% to 14% of patients with pimozide, haloperidol, thioridazine and/or ziprasidone, which may increase the risk of cardiac arrhythmias, were found with a history of arrhythmia. Commercial (N = 7,310 ) PDP (N = 153,500) MAPD (N = 21,711) Medicaid (N = 8,109) Polypharmacy, n (%)175 (2.4)9,739 (6.3)774 (3.6)307 (3.8) Table 3. Prevalence of Antipsychotic Medication Polypharmacy References: 1.Domino ME, Swartz M. Who are the new users of antipsychotic medications? Psychiatr Serv. 2008;59(5): Von Korff M, Wagner EH, Saunders K. A chronic disease score from automated pharmacy data. J Clin Epidemiol. 1992;45: N = 2,891 N = 20,125 Medical claims were not available to evaluate off-label use or drug disease interactions in PDP or Medicaid patients. FDA-approved conditions may be under-reported in claims data or may have been coded outside of the review period. Not all drug-disease interactions could be captured in this study. Limitations