Treatment Adherence Associated With Conventional and Atypical Antipsychotics in a Large State Medicaid Program Joseph Menzin, Ph.D. Luke Boulanger, M.A. Mark Friedman, M.D. Joan Mackell, Ph.D. John R. Lloyd, B.S.
Objectives: Rates of medication adherence over a one-year period were assessed among outpatients with schizophrenia who initiated therapy with conventional or atypical antipsychotic agents. Methods: Data were drawn from paid medical and pharmacy claims for a random sample of 10 percent of all California Medicaid (“Medi-Cal”) recipients. Outpatients with schizophrenia who were aged 18 years or older and who initiated monotherapy with a conventional or atypical antipsychotic medication in the last quarter of 1997 were identified. The percentages of patients who discontinued antipsychotic therapy or who had a switch in medications over a one-year period were determined. The use of selected concomitant medications was also assessed. Data were analyzed by means of chi square tests and multivariate statistics that adjusted for demographic and clinical differences between medication groups. Results: A total of 298 patients who initiated therapy with a conventional (N=93) or atypical (N=205) antipsychotic medication were identified. The groups were similar in mean age (about 42 years) and gender distribution (about 54 percent were male). Compared with patients who received conventional antipsychotics, those receiving atypical antipsychotics were significantly less likely to have a switch in medication and to use concomitant anticholinergic and anxiolytic medications. In each group, antipsychotic medication was available for about 60 percent of days over one year of follow-up. Conclusions: Compared with the use of conventional antipsychotics, the use of atypical antipsychotic medications was associated with significantly less treatment switching and less use of concomitant medications. However, undertreatment, evidenced by a lack of prescription refills, occurred among patients taking both medication classes, which highlights the need for further research on nonadherence. (Psychiatric Services 54:719–723, 2003)
S
chizophrenia, a devastating chronic mental disorder affecting nearly 1 percent of the U.S. population, is characterized by psy-
chotic symptoms that often result in hospitalization (1,2). Relapses of acute symptoms are common and have been estimated to result in costs
Dr. Menzin, Mr. Boulanger, and Dr. Friedman are with Boston Health Economics, Inc., 20 Fox Road, Waltham, Massachusetts 02451 (e-mail,
[email protected]). Dr. Mackell is with Pfizer Outcomes Research in New York City. Mr. Lloyd is with John R. Lloyd and Associates in Benicia, California.
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to the U.S. health care system of almost $2.3 billion annually (in 1993 dollars) (3). The social burden is higher still, because most patients with schizophrenia are unemployed (4). Until recently, the management of the symptoms of schizophrenia relied on the use of a number of conventional antipsychotic agents, such as haloperidol and chlorpromazine. These drugs are relatively effective in controlling symptoms but often produce adverse effects, especially extrapyramidal symptoms and, less commonly, tardive dyskinesia (5). Poor tolerability is thought to be associated with nonadherence to therapy, which is a significant problem for patients with schizophrenia. Adverse events are among the more common reasons cited for poor compliance with conventional antipsychotic therapy or for discontinuation of conventional antipsychotics (6–10). Medication nonadherence is the best predictor of relapse after a psychotic episode (6) and thus is an important clinical and public health issue. Previous studies documented low rates of medication adherence among patients with schizophrenia who use conventional medications. In one study, patients receiving conventional antipsychotics filled prescriptions for an average of 50 percent of prescribed doses, with a range from 20 to 90 percent (11). In another study, only 11 percent of patients with schizophrenia who were receiving conventional agents achieved uninterrupted thera719
py; the mean duration of uninterrupted therapy was 142 days over a year (12). More recently, a new class of agents —the atypical antipsychotics—has been introduced. These medications are potentially more efficacious than conventional antipsychotics and have a lower incidence of central nervous system adverse effects, such as tardive dyskinesia (13,14). The first drug in this class, clozapine, was introduced in the 1970s. Although clozapine is associated with greater efficacy compared with conventional antipsychotics (14), the potential for serious hematologic side effects and the requirement for weekly monitoring for such effects have limited its clinical use. In the past several years, other atypical antipsychotics—risperidone, olanzapine, quetiapine, and ziprasidone—have been introduced in the United States. Limited data are available for comparing the medication adherence associated with atypical agents versus conventional treatment. In one study, prescription refill records for an eightmonth period were analyzed to investigate compliance with various classes of antipsychotic medication (15). Forty-four and 48 percent of patients continued to refill their prescriptions for atypical and conventional antipsychotic agents, respectively. However, this study had several shortcomings, especially a lack of medical claims data that would have allowed identification of the underlying diagnosis for which the medications were prescribed. In this instance, the results of the study may have been affected by differential prescribing of atypical versus conventional antipsychotics for certain diagnoses, such as dementia, acute psychoses, and depressive psychoses, that do not warrant long-term treatment. To further explore adherence to antipsychotic therapy, we undertook a retrospective analysis of linked pharmacy and medical claims data for patients with schizophrenia in the California Medicaid (“Medi-Cal”) program who were initiating therapy with an antipsychotic medication. In late 1997, Medi-Cal removed restrictions on the use of atypical antipsychotics, thus providing an ideal opportunity to evaluate adherence to alternative therapies under typical practice conditions, including equivalent access to 720
all antipsychotic medications. We focused on three questions. First, how do the characteristics of patients who receive conventional antipsychotics compare with those of patients who receive atypical antipsychotics? Second, are rates of therapy switching and discontinuation different among users of the two types of medication? Third, does prescribing of concomitant psychotropic medications differ between these two groups of patients?
Methods Data source This study was based on data on eligibility and paid medical and pharmacy claims for a 10 percent random sample of Medi-Cal recipients. Medi-Cal, which covers more than 7 million persons, is the largest state Medicaid program in the United States. Total expenditures for the program exceeded $14 billion in 1998 (16). Many types of health care services are covered by the program. In 1998 (16), the most expensive services included hospitalization ($2.5 billion), nursing home care ($2.2 billion), physician services ($.7 billion), and prescription medication ($1.6 billion) (16). This analysis was based on data on eligibility and paid claims for prescription drugs, inpatient medical services, and outpatient medical services. The claims data for prescription drugs included National Drug Code numbers, dispense dates, quantities of medication dispensed, and number of days supplied. Inpatient medical services contained a primary diagnosis, up to two secondary diagnoses in ICD-9CM (17) format, and dates of admission and discharge, while outpatient medical services included the primary diagnosis and service date. The eligibility file included age and gender as well as a monthly history of Medi-Cal eligibility. The data used in this study were obtained for the period from 1996 to 1998. Patients The patients included in this study met the following eligibility criteria: age of 18 years or older; initial receipt of oral monotherapy with a conventional or atypical antipsychotic as an outpatient between October 1 and December 31, 1997 (the index period, PSYCHIATRIC SERVICES
with the first dispense date denoting the index date); no prescriptions for the same medication in the preceding year; a diagnosis of schizophrenia (ICD-9-CM codes 295.0x through 295.6x and 295.8x through 295.9x) or schizoaffective disorder (ICD-9-CM code 295.7x) listed on a medical claim in the year before the index date; and continuous Medi-Cal eligibility from one year before to one year after the index date. We chose to focus on patients who were starting a new medication—those who had not taken an antipsychotic medication or had taken a different agent in the previous year—rather than those who continued to take the same drug, because the rate of adherence to therapy may have been artificially high in the latter group. Patients were assigned to cohorts on the basis of the first new agent they received during the index period. For atypical antipsychotic agents, we focused on risperidone and olanzapine, the most widely used agents in the class during the study. Study measures Treatment discontinuation and switching. Patients who discontinued the medication they had first received during the index period were identified on the basis of having no record of a prescription refill for that medication in the last six months of the one-year follow-up period. For those who discontinued medication, we also determined whether their treatment was switched to another antipsychotic agent or whether the patient discontinued use of all antipsychotics. Patients who discontinued use of all antipsychotics were identified on the basis of having no record of a prescription refill for any antipsychotic in the last six months of the follow-up period. Persistence with therapy. Treatment persistence was assessed in terms of the number of covered days—that is, the number of days the medication was available—over the course of the one-year follow-up period. Use of selected concomitant medications. The use of concomitant therapies was evaluated before and after the start of the medication initiated during the index period. The concomi-
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tant therapies of interest included antidepressants, anxiolytics, mood stabilizers, and anticholinergics for the treatment of extrapyramidal side effects. We assessed changes in the number of patients who received each specific concomitant medication between the baseline and follow-up year. Data analyses Descriptive analyses were undertaken to evaluate differences in characteristics between patients receiving conventional antipsychotics and those receiving atypical agents as well as differences in doses of atypical antipsychotics. We estimated the likelihood of discontinuation and therapy switching on both an unadjusted and adjusted basis. The unadjusted analysis used chi square tests, and the adjusted analysis was based on logistic regression analysis. In the multivariate analyses, the independent variables included age, gender, additional psychiatric diagnoses, type of antipsychotic medication initiated during the index period (conventional or atypical), whether antipsychotics had been prescribed in the previous 12 months, the number of unique medications prescribed in the previous 12 months, and hospitalizations in the previous year (none versus one or more). The use of concomitant medications during the follow-up period was assessed with logistic regression that controlled for the independent variables listed above as well as whether these medications had been prescribed in the previous 12 months. Medication persistence was evaluated with t tests and multivariate analyses of covariance with the same set of predictors. The analyses of data were conducted by using PC SAS Version 8.0 (SAS Institute, Cary, North Carolina).
Results Patients’ characteristics A total of 9,853 patients were treated with a conventional or atypical antipsychotic between October 1, 1997, and December 31, 1997. A total of 7,989 of these patients (80 percent) were excluded from the analysis because they were continuing with a previously prescribed therapy. An additional 1,566 patients were excluded because they were receiving a combination of PSYCHIATRIC SERVICES
Table 1
Baseline characteristics of outpatients with schizophrenia in the California Medicaid (Medi-Cal) program who initiated therapy with an atypical or a conventional antipsychotic medication during the last quarter of 1997
Characteristic Agea 18 to 34 years 35 to 64 years 65 or older Gender Male Female Additional psychiatric disorders in the previous 12 monthsb Bipolar disorder Depression Dementia Substance use or abuse Psychosis not otherwise specified Dually eligible for Medicare Hospitalized in the previous 12 months For psychiatric reason For any reason Medications received in the previous 12 months Antipsychotics None Conventional Risperidone Clozapine Olanzapine More than one antipsychotic Concomitant medicationsb Antidepressant Anxiolytic Mood stabilizer Anticholinergic a b
Initiated therapy with an atypical antipsychotic (N=205)
Initiated therapy with a conventional antipsychotic (N=93)
N
%
N
%
51 145 9
25 71 4
29 59 5
31 63 5
110 95
54 46
50 43
54 46
42 69 2 31 77 68
21 34 1 15 38 33
15 22 1 27 36 32
16 24 1 29 39 34
21 42
10 21
11 18
12 19
79 105 9 5 1 6
39 51 4 2 –1 3
60 19 1 0 0 13
65 20 1 — — 14
93 42 61 116
45 21 30 57
36 14 33 36
39 15 36 39
Mean±SD ages were 41.9±11.4 years for the patients initiating therapy with an atypical antipsychotic and 42.5±13.1 years for the patients initiating therapy with a conventional antipsychotic. Patients may have more than one characteristic in the category.
agents (N=427), were not adults with schizophrenia or schizoaffective disorder eligible for the entire study period (N=1,071), or had recently been hospitalized (N=68). The remaining 298 met all inclusion criteria. Of these, 93 received a conventional antipsychotic and 205 an atypical antipsychotic. The two groups of patients were similar demographically (Table 1). Both groups had a mean age in the early 40s, and slightly more than half of the patients were men. However, the groups differed in distribution of additional psychiatric diagnoses; bipolar disorder and depression were
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more common among the patients starting atypical antipsychotic therapy, and substance use or abuse was more common among the patients starting conventional antipsychotic therapy. Moreover, approximately two-thirds of the patients for whom conventional therapy was prescribed (N=60) were not treated with antipsychotics in the previous year, compared with about 40 percent (N=79) of those receiving atypical antipsychotics. Most patients who received atypical agents were starting these medications as a result of a switch from conventional medications. In 721
Table 2
Changes in antipsychotic therapy over one year among outpatients with schizophrenia in the California Medicaid (Medi-Cal) program who initiated therapy with an atypical or a conventional antipsychotic medication during the last quarter of 1997
Change in therapy Discontinuation of antipsychotic initiated in the last quarter of 1997 Switch to another antipsychotic Discontinuation of all antipsychotics a b c
Initiated therapy with an atypical antipsychotic (N=205)
Initiated therapy with a conventional antipsychotic (N=93)
N
%
N
%
Crude odds ratioa
Adjusted odds ratioa,b
95% CIc
p
68
33
54
58
.57
.31
.18–.54
