These data demonstrate a relatively high prevalence of treatment non-adherence among individuals with BPD receiving treatment at a CMHC, and suggest that comorbid substance abuse, negative attitudes towards mood stabilizing medication, and difficulty managing to take medication in the context of one's daily schedule are primary determinants of medication treatment adherence. In this CMHC-treated sample, approximately 1 in 5 individuals identified themselves as being non-adherent with mood stabilizing medications to a clinically significant degree (missing 30% or more medications in the recent past).
Treatment non-adherence sharply increases personal, social and financial costs among individuals with BPD [46
]. Begley and colleagues [46
] noted that health care costs for severe/relapsing BPD (often characterized by non-adherence with prescribed treatments and comorbid substance misuse) is approximately $264,785 per person compared with $11,720 for individuals who experiences only a single manic episode [46
]. Similarly, Durrenberger and colleagues [48
] reported that over a 6- year period, the cost of care for one non-adherent patient with frequent manic relapses was equal to that for 13 adherent individuals. Identification of potentially changeable variables that are associated with treatment non-adherence in bipolar populations offers the potential to design interventions that address these areas of concern, and potentially to minimize the negative consequence for individuals with bipolar disorder who are at risk for stopping their medication treatments.
In common with some other investigators [20
], our study found few demographic or clinical variables that are clearly associated with non-adherence among patients with BPD. Identifying individuals at risk for future non-adherence thus goes beyond the need to focus on any specific age, gender or ethnic sub-groups. An exception to the similar demographic and clinical findings between adherent vs. non-adherent patients with BPD is more substance use among those who are non-adherent. Alcohol and other substance use disorders complicate the course of and prognosis of BPD [49
], and in most instances, treatment adherence is reduced among individuals with BPD who abuse substances [51
]. Large, epidemiological surveys of the general U.S. population have found BPD to have the highest association with alcohol or other psychoactive substance use disorders compared to other Axis I psychiatric disorders [52
]. Unfortunately, substance use comorbidity among patients with bipolar disorder may be under-recognized, and is often not addressed within the context of treatment for bipolar disorder. It has been demonstrated that individuals with more serious mental illness (including bipolar disorder) and co-existing substance use disorders are extensive users of costly crisis/emergency room care and inpatient services [54
]. However, the literature on evidence-based treatments for individuals with bipolar disorder and substance abuse is quite limited [55
Our study findings suggest that individuals who are non-adherent have negative attitudes towards medications, have difficulty managing medication routines and have more perceived reasons for non-adherence compared to adherent individuals. These are likely shaped by how the individual interprets and personally experiences bipolar illness. Models of health behaviors, such as the Health Belief Model [56
] focus on determinants of adherence as a product of an individual's health beliefs. The fact that there was little symptom difference between adherent and non-adherent individuals in the study presented here supports the notion that adherence attitudes may be relatively independent of symptoms (particularly in the case of bipolar depression) and are more a product of the individual's established health beliefs. Perceptions of susceptibility to illness, perceived severity of illness, the benefits of treatment, the costs and burdens of treatment as well as cues to action all factor into treatment adherence outcomes [57
In the population presented here, the strongest attitudinal predictors for non-adherence were difficulties with medication routines (OR 2.2) and negative attitudes towards drugs in general (OR 2.3). Individuals had difficulty always remembering to take medications, easily forgot their medication if they had a change in daily routine, and at times needed reminding by others to take their medications. Negative attitudes included the notion that taking medication for someone with BPD was not indicated or normal, and that the disorder might be best managed in other, perhaps non-pharmacological ways. These represent areas in which specific therapeutic interventions may be of benefit. The complexity of a treatment regimen can often affect treatment adherence [58
]. For example, adherence may improve when an individual is prescribed a pill that can be taken once daily rather than in divided daily dosing [59
]. When frequency of drug regimen is not modifiable, timing of medication can be matched to an individual's activities of daily living to improve adherence. Misinterpretation of common medication instructions can be addressed to improve treatment adherence. For example, Eraker [60
] noted that only 36% of patients correctly interpreted the meaning of “every six hours”. In addition to careful review of medication instructions, adherence aids such as pill boxes/pill reminders and pre-set dose alarms [60
] can be helpful. Compensatory strategies to enhance functioning in patients with schizophrenia have been successfully utilized by Velligan and colleagues [61
], and many of these methods appear likely to benefit bipolar patients with functional deficits as well [62
Inadequate or incorrect understanding of illness and treatment needs are not uncommon in populations with serious mental illness, including individuals with BPD [63
], and lithium knowledge has been demonstrated to be correlated with serum lithium levels [65
]. One study of psychiatric inpatients found that more than half of psychiatric inpatients did not know the condition for which they were being treated, the names of the medications prescribed, or the role the medications had in addressing the illness [66
]. Lack of communication or poor treatment alliance with providers may result in perpetuation of false beliefs regarding prescribed medications, which if addressed, could result in improved adherence [67
]. For example, fear of becoming “addicted” or dependent upon mood stabilizing medications may become an issue that affects adherence for some individuals with BPD [13
]. Psychosocial interventions that enhance knowledge and understanding of BPD, such as the Psychoeducational approach refined by Colom and colleagues [68
] may simultaneously improve both treatment adherence and more global illness outcomes.
The literature suggests that concerns over medication adverse effects is a major reason for non-adherence [4
], and that fear of side effects may play a larger role in treatment non-adherence among patients with BPD compared to the actual side effects themselves [19
]. Recent studies in large populations of individuals with bipolar disorder noted that non-adherence rates are remarkably similar across a wide variety of medications including traditional mood stabilizers and atypical antipsychotics [69
]. The medication concerns perceived by an individual may play a more important role in determining adherence rather than the specific type of medication prescribed. A recent survey of 233 members of the Manic Depression Fellowship [71
] noted that over 60% of individuals were dissatisfied with information about the risks of side effects with their medication treatments. Clear and readily understandable information on medication treatments with ample opportunity to provide feedback and address ongoing medication concerns may improve treatment adherence.
There is evidence to suggest that exploration of an individual's beliefs about bipolar illness and then implementing a therapy that directly addresses these beliefs may lead to changes in treatment planning and improve attitudes and adherence to mood stabilizers [72
]. This study found that non-adherent individuals more often had a strong powerful external locus of control compared to adherent individuals, contrasting with some previous reports in bipolar populations which found that adherence was more often associated with dependence on others or being more readily controlled/affected by others [18
]. However, this study also did not evaluate specific qualities of the types of social environment individuals in this sample experienced. It is possible that external or social influences may have not been supportive of medication taking in this group of individuals with BPD—a recent qualitative analysis by this group of investigators found that up to 40% of patients with BPD reported that family members or others specifically advised them against taking medications [6
]. An approach like Bauer and colleagues' [74
] Collaborative Care Model (CCM), in which individuals with BPD are actively involved in care planning/self-management is associated with better outcomes than more traditional medical-model care. A CCM approach may also promote positive and constructive alliances with care providers that enhance adherence in individuals with external locus of control. Likewise, family-focused therapy that includes education, communication training and problem-solving skills training for individuals with bipolar disorder is associated with better medication compared to less intensive crisis management [76
Our study has a number of important limitations including cross-sectional design and relatively small sample size. It is very likely that our analysis identified only a “lower boundary” of non-adherence given the possible under-detection of non-adherence when relying upon self-report. Additionally, expressed attitudes towards medication and adherence as evaluated on rating scales may not identify actual attitudes that individuals may be reluctant to share. Interpretation of study results can not be extrapolated to all bipolar populations who are non-adherent. Our study did not specifically focus on recruiting individuals who are non-adherent, and the most non-adherent patients are unlikely to volunteer to participate in a research study. Additionally, while adherent vs. non-adherent populations in this sample did not appear to differ substantially on symptoms, the study enrolled only individuals with bipolar depression, and it is possible that if individuals with mania were included the findings would have been different.