Medication adherence plays a key role in patients with bipolar disorder.7
Several specific factors associated with nonadherence in bipolar disorder have been reported, including young age, male gender, lower education level, being single, comorbid alcohol and drug abuse, psychotic symptoms during mania or mixed episodes, cognitive impairment, lack of insight, poor attitude towards medication, and work impairment.11
Better understanding of the factors involved in suboptimal adherence with medication for bipolar disorder is crucial because modifiable risk factors could become targets for future interventions.
However, many problems arise when conducting research in this area. Medication adherence is difficult to define and measure. Most methods used to measure adherence are considered to be indirect, such as self-reporting by patients, medication measurements, use of electronic monitoring devices, and prescription record review. Unfortunately, no measure can be accepted as the “gold standard”, because all methods have inherent limitations.7
Therefore, we decided to assess treatment adherence using a combination of three different, well known indirect scales, ie, DAI-10, MAQ, and CRS. Finally, the results of this study show a high prevalence of suboptimal treatment adherence in a sample of outpatients with bipolar disorder treated with at least one antipsychotic drug (n = 210, 69.3%).
An interesting finding in our study was that depressive polarity of the most recent episode predicted treatment non-adherence (OR 3.41, P
= 0.016). Linke et al recently reported that patients with bipolar disorder who last experienced a depressive episode learned better from negative feedback than from positive reinforcement.31
These authors suggested that, in addition to cognitive impairment, motivational vulnerability depending on polarity of the last episode is present in euthymic patients.
Disease severity (YMRS, MADRS, CGI-BP Mania and Depression) was significantly worse in patients with suboptimal adherence as compared with the adherent group. De Dios et al found that patients with bipolar disorder were in an episode one third of the time, and were symptomatic (in an episode or with subsyndromal symptoms) in one third of visits during 72 weeks of follow-up.32
Persistent subsyndromal symptoms increase the risk of and shorten the time to affective relapse in bipolar disorder.33
In our study, the presence of subthreshold symptoms was a predictor for suboptimal adherence (OR 2.13, P
Patient outcomes had traditionally been more focused on symptomatic remission. However, patient functioning is now considered to be one of the essential objectives when bipolar patients are treated.2
In our study, patients with suboptimal adherence had greater functional impairment, as measured by FAST, than patients with optimal adherence. Because patients with suboptimal adherence were also more symptomatic, only an association between adherence and functioning can be suggested. Further research is needed to establish the role of treatment adherence in functionality of patients with bipolar disorder.
Our study has several limitations. First, a cross-sectional study cannot confirm associations between the factors studied and must be limited to their descriptive and exploratory value or to generate hypotheses that should be confirmed in prospective follow-up studies. Second, treatment adherence was measured using indirect scales (two patient-rated and one physician-rated). Several methods for measuring adherence are available, each with its own set of limitations.34
Although Jonsdottir et al reported agreement between subjective and objective assessments of adherence, it is conceivable that we may have overestimated actual adherence.35
It has recently been suggested that a mixed method, incorporating both objective and subjective methods to assess adherence, may be the most reliable option.36
Third, the categorical approach to analysis of DAI-10 scores could limit the finding of additional correlations. Fourth, the sample population comprised patients taking an oral antipsychotic drug, so the results may not be generalized to include patients receiving treatment based only on mood stabilizers. Finally, neither insight into illness nor prior experience with psychopharmacological treatments and side effects were assessed as factors associated with treatment adherence.7
This study found a high prevalence of suboptimal adherence with treatment by bipolar outpatients seen in real-life practice. In this context, our results emphasize the importance of identifying patients with potentially modifiable risk factors for adherence-focused psychoeducational interventions.37