Source: Psychotropic Medications for Patients With Bipolar Disorder in the United States: Polytherapy and Adherence Ross Baldessarini, Henry Henk, Ami Sklar, Jane Chang, and Leslie Leahy, Psychiatr Serv 2008 59: 1175-1183
Medication Regimen Adherence And The Bipolar Disorder Polytherapy Trend
In the 1970s when I began my residency in psychiatry, a movement denouncing the scourge of polypharmacy in the treatment of psychiatric disorders was being mounted in the literature. Not long afterward, those physicians who tended to use only one medication for the treatment of these same disorders were similarly criticized. This is not necessarily a matter of clinicians succumbing to fads (although medical professionals are as susceptible as others to unscientific influences, including peer pressure); advances in research, changes in the concepts of a given pathology or the criteria of successful treatment, and the development of new biological agents may cause shifts in the recommended course of treatment.
In any case, the use of a combination of medications in the treatment of bipolar disorder is currently in favor.
In addition, the popularity of the diagnosis of bipolar disorder has steadily increased. Over the past 10 years, according to Moreno and colleagues,((Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007 Sep;64(9).)) clinic visits by adults that resulted in a diagnosis of bipolar disorder doubled and visits by children and adolescents that resulted in that diagnosis increased by a factor of 40.
Consequently, the widespread - but not universally held - contention that adherence to medication regimens decreases as the complexity of a dosage schedule increases makes the examination of compliance by this group of patients especially important.
The Study
Baldessarini and colleagues studied national health plan claims data (2000–2004) of 7,406 patients with bipolar disorder (bipolar I: 55%, bipolar II: 15%, bipolar disorder not otherwise specified: 30%).
I have excerpted some of the findings pertinent to compliance:
Treatment adherence
Additional new findings included identification of factors independently and significantly associated with long-term adherence to an initial mood-stabilizing treatment. Perhaps not surprisingly, only a minority (30%) of U.S. patients diagnosed as having bipolar disorder were nominally continued for a year on an initial mood stabilizer, and only 28% of this subsample were considered to be treatment adherent, on the basis of an MPR =80% averaged over 12 months.1 Factors associated with greater treatment adherence included being older, use of lamotrigine or lithium, lack of substance abuse, and treatment by a psychiatrist rather than a primary care physician. Inferior adherence was associated with use of valproate (the most commonly prescribed anticonvulsant mood stabilizer), use of carbamazepine or oxcarbazepine, use of supplemental anticonvulsants that lack FDA-approval for use in bipolar disorder, alcohol or drug abuse, and greater illness complexity.
… However, no significant association were found between MPR and co treatment with antidepressants or antipsychotics, nor with sex, diagnostic subtype, comorbidity index, or geographical region.
… Finally, we found complex associations between treatment adherence and utilization of health services. Office, and especially emergency service, visits for bipolar disorder–related care were more frequent in association with greater treatment adherence, whereas emergency service utilization for other indications and days per year of hospitalization for any reason were lower with greater adherence to mood stabilizer treatment). The lesser utilization of emergency and inpatient services suggests potential cost savings with greater adherence to mood-stabilizing treatments. On the other hand, greater use of ambulatory and emergency services for bipolar disorder–related indications suggests that greater treatment adherence may reflect relatively close monitoring, with more frequent clinician contacts. However, the available data do not permit clarification of cause-effect relationships between treatment adherence and utilization of clinical services.
Conclusions
… Adherence to long- term mood stabilizer treatment, although uncommon, was associated with several plausible clinical factors. Our findings of heavy reliance on antidepressants and polytherapy, low mood stabilizer utilization and adherence rates, and high rates of dropout from long-term mood-stabilizing treatment strongly suggest that more effective and better-tolerated mood - stabilizing treatments are required for patients with bipolar disorders, along with redoubled educational efforts to underscore the importance of sustained, longterm prophylactic treatment of such patients, even through periods of relative euthymia.
Commentary: Sadly, No Surprises
It is important to keep in mind that, as indicated in the article, the study used claims data as the information source and, congruently, defined adequate adherence as a medication possession ratio (MPR = the percentage of the past 365 days with apparent access to the medication) of at least 80%. This methodology is a rational research approach but is subject to limitations, one of which is that access to medication tends to define the maximum number of patients who may actually take sufficient amounts of their medication (i.e., patients cannot take their medications if they don’t have access to them, but having access to medication does not necessarily mean those medications were administered appropriately).
The most significant finding is also the least surprising: Of the 30% of patients diagnosed as having bipolar disorder that were, on paper at least, continued for a year on an initial mood stabilizer, only 28% were found to be adherent.
The associations between treatment adherence and utilization of health services is, as the authors note, “complex.” The connection between better adherence and decreased use of emergency service utilization for indications other than those related to bipolar disorder and days per year of hospitalization are heartening. But, as the article points out, one cannot establish a cause-effect relationship. It may be, for example, that, as other studies have suggested, patients who tend to be adherent to treatment are also healthier, independently of the effects of their treatment.
I am also hesitant to subscribe to the authors’ positive spin on the data reflected in their speculation that “… greater use of ambulatory and emergency services for bipolar disorder–related indications suggests that greater treatment adherence may reflect relatively close monitoring, with more frequent clinician contacts.”
Other explanations are possible. One alternative hypothesis, for example, is that a subgroup of noncompliant patients whose family or friends assure that doctors’ appointments are kept and that the patients are taken to the ER during exacerbations of their disorders might also be more likely to have prescriptions filled, again because of the insistence and assistance of friends and family. Those patients, who might rarely take the medications, would be accounted adherent because the medications are accessible to them.
Of course, the difference in those interpretations may have less to do with a cognitive assessment of the data than with the difference between the research team’s world view and my own perspective.
Those differences could also explain my lack of enthusiasm for the paper’s recommendations that “more effective and better-tolerated mood - stabilizing treatments are required for patients with bipolar disorders, along with redoubled educational efforts to underscore the importance of sustained, longterm prophylactic treatment of such patients, even through periods of relative euthymia.”
Before I start getting nasty emails, I will point out that I’m not against “more effective and better-tolerated mood - stabilizing treatment” or “redoubled educational efforts.”
I am, in fact, 110% in favor of producing treatments that are more effective for every disease, that are better tolerated by patients, that taste like cherry pie, and that render those patients more attractive, all of which could enhance compliance. I am also in favor of clean streets, lower taxes, an end to world hunger, and a World Series championship for the Cubs.
And, I’ll call your “redoubled educational efforts” and raise you a retripled educational effort. Heck, I’m willing to go as high as an exponentially increased educational effort. I just don’t find much evidence that quantum leaps in educational effort beyond a competent communication of information have a significant positive effect on compliance.
As explained in my introduction, adherence to polytherapy of bipolar disorder is an especially significant area and Dr. Baldessarini et al have provided an important confirmation of the catastrophically low proportion of bipolar patients who are receiving an adequate course of treatment.
I suggest, however, that the appropriate primary response to these findings is not better drugs and more patient education but further research that would explain why these results, that less than 30% of bipolar patients even have access to sufficient medication during the 12 months studied, isn’t on the front page of today’s New York Times and Chicago Tribune and broadcast as the lead story on CNN and the ABC Evening News.
Footnotes
__________- The research group measured adherence to mood stabilizers by using a medication possession ratio (MPR). MPR is the percentage of the past 365 days with apparent access to an initial mood stabilizer.↩