Despite a fairly constant rate of individuals in the US with mental illness (26
), there have been notable shifts in the population of non-institutionalized US civilians using antipsychotic medications. We found substantial increases in the number of individuals filling antipsychotic prescriptions in the general US population, but no increase in the level of use among antipsychotic users since the mid-1990s, measured by both daily dose units and by the number of prescriptions.
The relatively constant rate of use among individuals who self-report schizophrenia indicates that the rapid diffusion of second-generation antipsychotics was not associated with a greater rate of treatment in this population. Rates of antipsychotic use among those reporting schizophrenia were stable across years and no difference was found in reporting rates across years (p=0.685), although rates are lower than in other studies (27
). The expansion of the antipsychotic market, instead, occurred among other disease categories, such as those with 296-affective disorders.
The fact that the increased use of second-generation antipsychotics was not accompanied by a higher dosing is surprising and may mask several competing trends. Second-generation antipsychotics were originally touted as less-toxic alternatives to first-generation agents (28
), which, if true, should have increased the level of use. However, during the sample period, more information became available on the negative health effects of some second-generation antipsychotic medications, leading the FDA in 2003 to issue a warning regarding the risk of hyperglycemia and diabetes mellitus based on several studies which were published during our study period (31
). In addition, the remarkable increases in the rates of use for off-label conditions and use in children (5
) may lead to lower dosing.
The data examined here largely predate the CATIE results, but the question remains: why did second-generation antipsychotics diffuse so rapidly? The answer is complex, and is likely a function of factors not examined here, such as provider and patient expectations and preferences, drug company marketing effects (12
) and the dominance of industry-funded trials in the early second-generation antipsychotic efficacy literature (28
). In addition, clinical and malpractice risk concerns about the higher rate of tardive dyskinesia associated with first-generation vs. second-generation antipsychotics also drove diffusion. The trends here mimic the rapid diffusion of the newer antidepressant medication, especially among children (34
It is clear that the appropriate use of antipsychotic medications improve the quality of life for people with schizophrenia and related disorders (12
), but recent evidence from the CATIE and other studies (35
) has brought into question whether the more expensive second-generation antipsychotics are really a better use of resources compared to first-generation antipsychotics. The lower risk of tardive dyskinesia may be one area in which second-generation antipsychotics have an advantage of first-generation antipsychotics, although this is recently been questioned (35
) and may be overshadowed by the greater risk of diabetes, obesity, and other related conditions (4
); many of these risks were disclosed during our study period (38
). Second-generation antipsychotics will only increase in use as they begin to come off patent, opening the market for less expensive generic substitutes, and triggering a wave of less restrictive policies, especially in Medicaid and Medicare Part D formularies.
The greater use of antipsychotics in pediatric populations is consistent with other work (5
) and is an important policy issue. Antipsychotics are used in childhood disorders other than schizophrenia, such as autism and disruptive behavior disorders, but little is known about their efficacy and long-term effects and differences in the types and intensity of side effects have been noted (5
A number of limitations should be noted for this analysis. The MEPS does not survey institutionalized individuals, who may have different patterns of antipsychotic use. Therefore the size of the full antipsychotic market and specifically the amount paid by Medicaid are understated in this study. Several of the cells for 1996/97 are based on fewer than 100 observations and may be less reliable; they are presented for descriptive purposes only but this in itself is a telling indicator of the rates of use in these subpopulations in the earlier time period. The self-reported medical conditions are not as accurate as clinician diagnoses and clearly understate the prevalence of disease in the population. For example, Wu and colleagues (39
) estimate a 12-month prevalence of schizophrenia of 0.51% using a variety of claims data sources, whereas the MEPS reported prevalence is 0.16–0.18%. In addition, the on-label rates reported here, ranging from 27.5% in 1996/97 to 35.8% in 2004/5, are likely too low, although the inclusion of all 296 affective disorders as on-label underestimates off-label use. Other rates reported in the literature use claims diagnoses and are slightly higher, ranging from 36% in Georgia Medicaid in 2001 (39
) to 44% of second-generation antipsychotic use in 2004 (40
); Radley and colleagues report an off-label rate of 31% for the broader psychotropic category (9
). The conversion to daily dose units are based on current dosing guidelines and do not vary over the study period. We do, however, find consistent results whether we look at the annual number of daily doses or the number of antipsychotic prescriptions.
While literature from the CATIE study has increased the knowledge base surrounding the use of antipsychotic medications, there are a number of issues that remain to be examined. As with most clinical trials, the population studied in CATIE may not resemble the full spectrum of medication users (13
). In particular, users with schizophrenia and Alzheimer’s represent a small fraction (<20%) of all antipsychotic users. Further information on the cost-effectiveness of antipsychotic use in these non-traditional but increasingly common categories of use would inform the diffusion process. Finally, while CATIE itself may affect antipsychotic diffusion, early results in a privately insured population found no effect of CATIE on antipsychotic use (41
). Inferences from CATIE were complicated by the introduction of Medicare Part D shortly after the initial CATIE results were released; Part D itself will also substantially affect the use of antipsychotic medications as Medicaid funding and associated restrictions on medication use for dually-eligible Medicare beneficiaries shifted to the Medicare program (42
). If prescribers become willing to return to the earlier technology of first-generation antipsychotics as the CATIE message is repeated, we may see a substantially different diffusion process over the next decade.