Among Florida Medicaid recipients, there were small decreases in overall SGA use after the FDA advisory and consensus statement publication. However, there were significant and sustained decreases in olanzapine use among both incident and prevalent SGA users. Our results are consistent with two prior evaluations assessing SGA prescribing, specifically regarding shifts in olanzapine use.8, 37
However, the current study expands upon prior efforts by evaluating the advisory and consensus statement’s impact on both specific agent selection and several important and potentially unintended outcomes including changes in overall SGA use, use of therapeutic substitutes, and treatment interruptions or discontinuations.
While anecdotal evidence suggests that patients may be at increased risk for discontinuations or treatment interruptions following the release of drug risk communications,12
we did not observe this in our sample. Instead, there were decreases in discontinuations and treatment interruptions through the initial post-advisory period. This is encouraging considering the importance of continuity of care among patients with severe mental illness.
Previous studies of the FDA advisory’s impact on metabolic risk have left the impression that the advisory was largely ineffective due to the low adoption of metabolic screening recommendations.16, 18, 19, 38
Coupled with our finding of little change in overall SGA use, one might conclude that the advisory had little effect on providers’ treatment decisions. However, there were substantial changes in drug utilization with major shifts away from olanzapine to drugs with lower known risk. Given the recent focus on preventing weight gain and metabolic syndrome in patients through selecting lower metabolic risk agents,39
these results are promising.
While the importance of screening and monitoring patients for metabolic adverse effects should not be minimized, neither should the importance of agent selection. Patients taking SGAs or other agents requiring laboratory monitoring or clinical follow-up may face important barriers to monitoring, including a fragmented medical system,40
provider discomfort or lack of knowledge about the patient’s general medical conditions (for mental health clinicians)41
or mental health conditions (for primary care providers),42
and problems resulting from the patient’s mental illness (e.g., amotivation, cognitive limitations, poverty).40
These barriers may have led physicians to adopt a general policy of avoidance of higher metabolic risk agents. In fact, significant declines in olanzapine use occurred among enrollees with and without prior metabolic conditions, suggesting that high-risk agent use decreased among all patients, rather than among higher-risk patients alone. This explanation is supported by a recent study suggesting that selection of a lower-risk SGA was not consistently associated with abnormal laboratory values.7
Although olanzapine use rapidly decreased following the FDA’s advisory, these decreases were offset by significant increases in quetiapine use. Recently there has been concern that quetiapine may be associated with a higher metabolic risk than originally proposed in the consensus statement.43, 44
Given the high proportion of incident quetiapine use in our sample, this relationship should be further clarified.
Following the initial post-advisory period, several important market impacts occurred for SGAs. For example, from April–September 2005 the CATIE trial results were published (reporting olanzapine’s efficacy and association with weight gain and metabolic problems), the FDA added a black-box warning to SGAs regarding an increased risk for elderly patients with dementia, and Florida Medicaid temporarily shifted olanzapine onto a non-preferred drug list. These factors were associated with additional decreases in olanzapine use. By the end of the study period olanzapine use had decreased by 59% among prevalent users with bipolar disorder, and 64% among prevalent users with schizophrenia, while incident olanzapine prescribing declined, 81% and 83%, respectively.
Limitations include using Medicaid claims from a single state, which may limit generalizability if SGA users systematically differ across states. In addition, one prior study showed a large effect of Florida’s 2005 policy change on olanzapine prescribing.45
Although our primary focus is on assessing changes prior to this policy change, estimates from later study periods may be lower than in Medicaid programs without similar policies. Next, while we observed changes in SGA selection following the FDA advisory and consensus statement, the effect cannot be separated from other policy and market impacts. Changes in pharmaceutical firms’ promotional strategies, Medicaid policies, and publication of new safety and effectiveness information all play a part in increasing or decreasing overall utilization of a pharmaceutical product. Although we control for known Medicaid policy changes and timing of major publications, press releases, and additional advisories, other unobserved factors may have influenced our results.
Overall, there were significant shifts in SGA use among Medicaid enrollees with severe mental illness following the FDA advisory and consensus statement publication. Although metabolic screening and monitoring recommendations have not been effective, sweeping changes in higher-risk metabolic agent use suggest that many clinicians and patients were aware of and responded to the metabolic risks associated with these medications.