Diagnosis and Treatment of Bipolar Disorders in Adults: A Review of the Evidence on Pharmacologic Treatments

Bipolar disorder is a chronic, relapsing illness characterized by recurrent episodes of manic or depressive symptoms, with intervening periods that are relatively (but not fully) symptom-free. Onset occurs usually in adolescence or in early adulthood, although onset later in life is also possible.1 Bipolar disorder has a lifelong impact on patients’ overall health status, quality of life, and functioning.2 This disorder has 2 major types—bipolar disorder I and bipolar disorder II.3 Bipolar disorder I is defined by episodes of depression and the presence of mania, whereas bipolar disorder II is characterized by episodes of depression and hypomania. Therefore, the main distinction between the 2 types is the severity of manic symptoms: full mania causes severe functional impairment, can include symptoms of psychosis, and often requires hospitalization; hypomania, by contrast, is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization.3 Longitudinal studies show that patients with bipolar disorder of either type experience symptomatic depression at least 3 times more frequently than symptomatic mania or hypomania (Figure 1).4–9 The lifetime prevalence of bipolar disorder in adults in the United States is reported to be 3.9%.10 Figure 1 Total Time Ill in First 2 Years After the Index Episode KEY POINTS ▸ Bipolar disorder is a dynamic and serious condition that can have a lifelong impact on a patient's overall health status, quality of life, and functioning. ▸ The treatment of bipolar disorder is challenging and costs the US healthcare system an estimated >$30 billion in direct expenditures and >$120 billion in indirect costs annually. ▸ Delayed diagnosis can result in worsening clinical outcomes and increased costs; early recognition of this condition can reduce the total per-patient costs by as much as $2316 annually. ▸ Considering the possibility of bipolar disorder in patients with depressive disorders is critical to improving outcomes and reducing costs of treatment. ▸ Despite the introduction of new therapies for bipolar disorder, treatment outcomes remain less successful than for major depressive disorder; the use of antidepressants for this condition remains controversial. ▸ Medication nonadherence is perhaps the most significant contributor to poor outcomes in this patient population; monotherapy may help improve adherence in some patients. ▸ The selection of an appropriate treatment that takes into account efficacy as well as safety can help to ameliorate the devastating impact of bipolar disorder. Bipolar disorder has an enormous economic impact on the US healthcare system.11,12 The estimated total direct cost of bipolar disorder (including inpatient costs, outpatient costs, pharmaceuticals, and community care) in the United States in 2009 was $30.7 billion.11 In addition, the adverse impact of bipolar disorder on functioning and quality of life translates to a substantial total indirect healthcare cost resulting from the loss of employment, loss of productivity, sick leave,13 and uncompensated care that is estimated at more than $120 billion annually.11 From a managed care perspective, bipolar disorder is among the most costly of all mental health conditions. In a major study of commercial insurance claims data from 1996 of almost 1.7 million individuals, although only 3% of patients with a mental health claim were identified with bipolar disorder, these patients accounted for 12.4% of the total plan expenditures.14 High cost was driven largely by a disproportionate rate of inpatient admissions for bipolar disorder versus all other behavioral health claimants (39.1% vs 4.5%, respectively), resulting in a cost of $1.80 for inpatient care per every dollar of outpatient treatment cost.14 Another large study of healthcare utilization and costs from 2004 to 2007 compared 122 patients with bipolar disorder with patients with other psychiatric conditions, including 1290 patients with depression, 2770 with asthma, 1759 with coronary artery disease, and 1418 with diabetes.12 The patients with bipolar disorder had higher adjusted mean costs per member per month (approximately $1700) than all other groups, including depression (approximately $1300), with the exception of patients who had both diabetes and coronary artery disease (with approximately $2000 per member per month).12 Despite the advent of lithium therapy more than 60 years ago,15 the introduction of other pharmacotherapies and the development of disease-specific behavioral approaches,16 and a generally greater awareness of bipolar disorder, treatment outcomes remain less satisfactory than the outcomes for major depressive disorder (MDD) in all sectors of the US healthcare system, including managed care.2 This represents a challenge and an opportunity for managed care to focus on this disorder to improve outcomes and to reduce healthcare costs. This review article presents the clinical evidence supporting best practice for the diagnosis and treatment of bipolar disorder. The review highlights what little is known about the most effective ways to address specific clinical challenges in caring for patients with bipolar disorder and identifies recent research that documents innovative approaches to improving the effectiveness of care in this setting.