Use pattern and off-label use of atypical antipsychotics in bipolar disorder, 1998-2002

Postmarketing surveillance that identifies patients at high risk for receiving off-label medications will help ensure that the benefits of such treatment outweigh the risks. Because many off-label uses have little scientific support, tracking the extent to which they occur as well as the particular circumstances under which they occur is important.

To describe the drug-use pattern for patients with bipolar disorder, and to identify demographic and clinical factors associated with off-label use of atypical antipsychotics before US Food and Drug Administration approval for this indication.

Using the PHARMetrics medical claims database, a total of 105,771 adult patients with a diagnosis of bipolar disorder were evaluated during the 5-year (1998-2002) study period. Study drugs included mood stabilizers, antipsychotics, and antidepressants. Off-label use of an atypical antipsychotic was defined as a patient taking olanzapine before March 2000 (when it received an indication for bipolar disorder) or any other atypical antipsychotic during the entire study period. Logistic regression analysis was used to determine the odds ratio of receiving a drug off-label.

Utilization of and reimbursement for atypical antipsychotics increased during the 5-year period. Of the 10.5% of patients who took atypical antipsychotics, 7.1% took these drugs off-label. In addition, 11% of patients received lithium, 25% received other anticonvulsants, and 34% received antidepressants. Off-label use of atypical antipsychotics was associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI, 1.44-1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51; 95% CI, 1.38-1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14-1.26), diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16-1.37), cerebral vascular disease (odds ratio = 1.26; 95% CI, 1.10-1.45), and hypertension (odds ratio = 1.12; 95% CI, 1.05-1.20). Over time, there has been an increase in the number of drug therapies, including atypical antipsychotics, used to treat bipolar disorder.

Because of the significant association found between atypical antipsychotic use and several key comorbidities, it is important for physicians to recognize these associations and weigh the risks and benefits of atypical antipsychotics in their treatment strategies.