In our study, patients with schizophrenia or bipolar disorder who were recently discharged from the hospital were found to have poor adherence over time with aripiprazole, quetiapine, and ziprasidone. Those with schizophrenia received medication sufficient to cover only about 55% of their follow-up days over 6
months (mean CMG), while those with bipolar disorder received medication sufficient to cover only about 37% of their follow-up days. Approximately one in four patients had evidence of therapy switching during the 6-month follow-up period.
Noncompliance is an important predictor of hospitalization risk. Following inpatient treatment and discharge from the community, many patients become poorly compliant with therapy [12
]. Several reasons for poor compliance have been hypothesized, including disease symptoms (e.g., grandiosity, paranoia, problems with accurate recall), treatment-emergent side effects, substance abuse, lack of support systems to encourage medication compliance, psychostressors, and poor patient-provider relationships [14
]. Previous reports suggest that more than one-half of all patients with schizophrenia become noncompliant with their medication regimen within one month of discharge from hospital [15
]; by 2
years following discharge, about 75% are noncompliant [15
]. Among patients with bipolar disorder, compliance is also low. In one retrospective analysis of healthcare claims data, Lage and Hassan report that 62% of patients with bipolar disorder newly started on antipsychotics had MPRs ≤50%, and that mean MPR was 41.7% [18
]. Rates of medication adherence were low in our study too.
We limited our attention to aripiprazole, quetiapine, or ziprasidone, as we believed these three SGAs to be relatively similar with respect to their adverse event profiles. Olanzapine and risperidone were excluded due to much higher reported rates of weight gain with the former, and extrapyramidal symptoms (EPS) with the latter [8
]. Our results suggest that adherence is not substantially better with these agents than with other SGAs (e.g., rates of discontinuation in the CATIE study ranged from 64% [olanzapine] to 82% [quetiapine]) [19
]. We note, however, that our study sample was small, which limits the generalizability of our findings. Further study is needed to better understand patterns of “real-world” adherence among patients prescribed SGAs upon discharge from hospital for schizophrenia and bipolar disorder, respectively.
This study has a few key limitations. For one, our sample size was small, principally because the study dataset was created by linking information from a health insurance claims database with data from a large inpatient data warehouse. Compounding this limitation was our decision to limit the study sample to patients with at least 6
months of eligibility for medical and drug benefits before and after the “qualifying” hospitalization, and to exclude patients with evidence of both schizophrenia and bipolar mania. Accordingly, the generalizability of our findings to all patients hospitalized for schizophrenia or bipolar disorder who are subsequently discharged on SGAs is unknown. On a related note, while prior research in both schizophrenia and bipolar disorder has established an inverse correlation between levels of adherence with antipsychotic medications and risk of relapse [20
], the relatively small number of patients in our study precluded an examination of this question.
Second, the healthcare claims database—the source for most of the information on patterns of utilization of study agents during follow-up—only allows the identification of prescription drugs dispensed by retail pharmacies (i.e., filled prescriptions and their associated therapy-days). We could not ascertain whether medications that were dispensed were actually taken. Thus, our estimates may represent an upper bound for the amount of medication actually taken. On the other hand, it should be noted that patients are sometimes discharged from hospital with a small supply (e.g., 3
days) of medication to insure continued use until they are able to fill a prescription at a retail pharmacy. Unfortunately, the database does not contain information on professional samples dispensed at hospital discharge. In our study, 39%, 56%, and 69% of patients in the schizophrenia cohort filled their first prescription for study agents within one, six, and 14
days of discharge from their qualifying hospitalization, respectively; corresponding values for patients in the bipolar cohort were 61%, 81%, and 82%, respectively. It is reasonable to assume that most of these patients were intent on continuing with the study agent received at discharge. Accordingly, our reliance on therapy-days as noted on paid claims from retail pharmacies likely understates the amount of medication actually taken. Further study is needed to better understand the degree to which patients with schizophrenia and/or bipolar disorder adhere to discharge therapy.
Finally, as with all database studies, there may be errors of omission and commission in coding. However, the case-finding algorithm (i.e., hospitalization with a principal diagnosis of schizophrenia or bipolar disorder, and initiation of SGA treatment at discharge) used in this analysis likely minimized the inclusion of patients who did not have schizophrenia or bipolar disorder therefore, the specificity of this algorithm is likely high.