Does Depression Increase Risk for Noncompliance with Warfarin Therapy?

Introduction

Management of warfarin therapy in an outpatient setting has been proven to be challenging despite specialized anticoagulation clinics. It is estimated that 40-50% of INR values are outside and, most commonly, below the therapeutic range. Extended periods of time spent outside the therapeutic INR range have been associated with an increased risk for morbidity and mortality. Sub-therapeutic INRs are associated with a higher risk for thromboembolism, which can lead to ischemic stroke and myocardial infarction; while supra-therapeutic INRs are associated with warfarin-induced hemorrhage, both of which can lead to an increased mortality. Furthermore, it has been found that patients with depressive symptoms have been associated with decreased adherence to any medical management when compared to non-depressed patients and patients with psychosocial or emotional factors are more often found to be outside therapeutic range while on warfarin therapy. However, whether depression has a direct effect on noncompliance with warfarin therapy has yet to be studied. This study intends to prove depression does increase the risk for noncompliance with warfarin therapy and, subsequently, increase their risk of adverse events due to decreased time-in-therapeutic range (TTR).

Method

A retrospective study was conducted on 91 patients from an outpatient anticoagulation clinic. INR data, past medical history of depression, demographics, and history of complications secondary to warfarin therapy were collected. Patients with history of depression were compared to patients without history of depression on their demographic variables, risk factors and the study outcomes. Chi-square tests were used to determine the significant difference between the two groups on categorical variables. The student t-tests were used to determine the significant difference between the two groups on continuous variables. A p-value ≤ 0.05 was regarded as significant. A logistic regression model was used to determine whether depression had an impact on keeping the patient’s INRs within the therapeutic range 70% of the time while on therapy. All the statistical analyses were completed by SAS version 9.2.

Results

We found that the group of patients with a history of depression were 67% less likely to have patients who had their INRs within the therapeutic range 70% of the time while on therapy when compared to patients without a history of depression (odds ratio=0.33, CI 0.116 – 0.935, p-value = 0.0370). Additionally, we found that patients with a history of depression had, on average, a lower TTR than patients without a history of depression (p-value = 0.0399).

Conclusion

The results reveal patients with a history of depression are at an increased risk for noncompliance with warfarin therapy when compared to patients without a history of depression. Furthermore, patients with a history of depression and on warfarin therapy would likely benefit from further interventions to increase their TTR and decrease their risks for adverse events.