In this retrospective claims-based study, more than half of the 7,769 patients with bipolar disorder took their antipsychotic medication less than half of the time (61.9% had an MPR of less than 0.50), with the vast majority (78.7%) taking their medication less than 75% of the time. These observations are consistent with previous research indicating low levels of adherence to antipsychotics [19
] and mood stabilizers [25
] among patients with bipolar disorder. Alongside these findings, higher levels of adherence to antipsychotic medication were found to be associated with better patient outcomes, both in terms of hospitalizations and visits to the ER.
An examination of hospitalization outcomes revealed that, as patients achieved a higher MPR threshold, the odds of hospitalization for any cause as well as mental health-related hospitalizations, decreased. For instance, patients who achieved an MPR threshold of at least 0.75 had an approximate 15% reduction in the odds of being hospitalized for any cause (p < 0.05), while those who achieved an MPR threshold of 0.90 or 0.95 had a 36% or 46% (both p < 0.05) reduction in the odds of hospitalization, respectively.
While no previous study of individuals with bipolar disorder has reported on the relationship between adherence to antipsychotic medication and patient outcomes, previous research among patients with schizophrenia has shown partial or non-adherence to antipsychotic medication to be associated with higher rates of hospitalization [26
]. In addition, several studies among patients with bipolar disorder have found a link between non-adherence to prescribed medication and hospitalization. An analysis of factors leading to hospitalization among elderly patients with bipolar mania found lack of adherence with prescribed psychiatric medication (for example, mood stabilizers) to be a major factor [14
]. A study of adherence and outcomes among patients with bipolar disorder who were receiving antipsychotics, lithium, and antidepressants reported hospitalization rates of 73% for those classified as irregular medication users compared with 31% for regular users [15
]. Similarly, an examination of adherence to mood stabilizers among individuals with mood disorders found hospital admission rates of non-adherent patients to be 81.2%, compared with a rate of only 9.7% among adherent individuals [16
], while another study found non-adherence to mood-stabilizing medication to be a cause of relapse among patients with bipolar disorder [27
]. Although these earlier studies did not primarily focus upon antipsychotic medications, the consistency of the findings indicates the importance of compliance to any treatment protocol.
Patients with an MPR of at least 0.75 had 16% lower odds of visiting the ER (p < 0.05), while those with an MPR of at least 95% had 38% lower odds of visiting the ER (p < 0.05). As observed with ER visits for any cause, an examination of the association between medication adherence and ER visits with an accompanying mental health-related diagnosis revealed that, as MPR thresholds increase, the odds of an ER visit decline. However, unlike the results for ER visits for any cause, a significant reduction in the odds of an ER visit for mental health reasons was not achieved until patients reached a threshold of at least 0.90 (OR 0.71, 95% CI 0.54 to 0.91). In comparison, an earlier study of the relationship between adherence to traditional mood-stabilizing therapy (lithium, valproate, carbamazepine, lamotrigine, oxcarbazepine) and health care utilization among patients with bipolar disorder, found adherence below 80% to be associated with a significantly greater risk of mental health-related ER visits (OR 1.98, 95% CI 1.38 to 2.84) [28
]. This difference in results may indicate that the adherence threshold is higher for antipsychotic medications than for traditional mood-stabilizing therapy, although further research is needed before reaching a definitive conclusion.
One advantage of this study is that it allowed for an examination of effects on patient outcomes with various adherence thresholds. This study is in contrast to previous studies that defined adherence based upon a specific MPR threshold without necessarily explaining the choice of such a threshold [29
]. Furthermore, it has been argued that 'the use of arbitrary categories of good and poor compliance (often set at 80%) usually was unsupported by research documenting the appropriateness of the cutoff for a specific medication class or disease' [32
The findings presented here should be interpreted within the context of the limitations of the study design. This analysis was conducted using an administrative claims database, and included only patients with medical and outpatient prescription benefit coverage. The results, therefore, may not generalize well to other populations. Additionally, the use of diagnostic codes may be less rigorous than formal diagnostic assessments for identifying patients. Although analyses were adjusted for differences in bipolar disorder type, general health, and comorbidities, it was not possible to control for disease severity. The utilization of medical claims data precluded the inclusion of patient assessments and thus outcome measures related to quality of life, caregiver burden, or any of the other indirect costs associated with bipolar disorder were not included in this study. This investigation examined adherence to antipsychotic medications alone and did not account for prescribed changes in treatment protocol. Therefore, patients switched by their physicians from an antipsychotic to a different type of drug during the study period would have been viewed as non-adherent, even if they were fully compliant with their prescribed therapy. Finally, this study focused on both atypical and conventional antipsychotics, without controlling for class or exact type of medication. However, the results were largely driven by atypical antipsychotic medications, as demonstrated by 95% of the patient population receiving this class of therapy.