This study estimated total antipsychotic medication costs in the usual care of patients with schizophrenia treated at various health care settings in the United States when initiated on 1 of 3 commonly used atypical antipsychotics – olanzapine, risperidone, and quetiapine. The 2 approaches used to calculate the costs were the average daily cost while the patient is on the initiated index antipsychotic and the total annual antipsychotic medication costs, reflecting intent-to-treat approach. The average daily cost on the index atypical antipsychotic was significantly higher for olanzapine compared to risperidone and quetiapine groups. However, due to the presence of antipsychotic polypharmacy, each dollar spent on the index antipsychotic was accompanied by an additional spending on other antipsychotics, such that each dollar spent on quetiapine was associated with an additional $1.31 for concomitant antipsychotics, compared to an additional $0.64 for risperidone and an additional $0.38 for olanzapine. Thus, despite the significantly higher medication acquisition cost of olanzapine, the average daily antipsychotic medication cost was found to be significantly higher for quetiapine ($15.33) compared to olanzapine ($13.90) and risperidone ($11.04).
Similarly, the intent-to-treat annual antipsychotic medication cost for patients initiated on olanzapine ($4536) and risperidone ($3813) was found to be significantly lower than that for patients initiated on quetiapine ($5320), a reduction in medication cost of $786 for olanzapine and $1507 for risperidone. Importantly, these total antipsychotic cost savings for patients initiated on olanzapine compared to quetiapine were achieved despite longer treatment duration with olanzapine at a higher drug acquisition cost.
The primary cost driver of the expensive antipsychotic polypharmacy practice associated with quetiapine therapy appears to be the rates and duration of coprescribed atypical antipsychotic polypharmacy. As reported in our previous study [15
], patients initiated on quetiapine had the highest rate and longest duration of antipsychotic polypharmacy among the 3 studied atypical antipsychotics, followed by risperidone and olanzapine, thus increasing the average daily and annual antipsychotic costs of treating patients with schizophrenia. Note that the higher antipsychotic medication costs associated with quetiapine therapy was achieved despite the relatively low dose of quetiapine used in this study. Low dose of quetiapine may explain its lower medication acquisition costs compared to olanzapine. In clinical practice, higher mean dose (620 mg) for quetiapine has been reported by Citrome and colleagues [30
]. There is the possibility that quetiapine was dosed too low in this study to be effective for some patients leading to unnecessary costs of additional antipsychotics. At the same time, the 2-fold increase in quetiapine dose will considerably increase its acquisition costs and overall medication costs.
To our best knowledge, this is the first study to assess the cost of antipsychotic polypharmacy in the usual care of patients with schizophrenia demonstrating that this common practice adds a substantial treatment cost and may even double the medication cost of antipsychotic medication regimens. Current findings are consistent with previous research [19
]. In a short-term, randomized, double-blind study of risperidone, placebo, and quetiapine for inpatients with schizophrenia [31
], clinicians were allowed to augment with other antipsychotics for a 4-week duration following 2 weeks of monotherapy. That study found the quetiapine group (mean dose 579.5 mg/day) to be significantly more likely augmented with another antipsychotic compared to risperidone, but without significant or meaningful clinical benefits. The mean cost of antipsychotic polypharmacy per randomized patient was almost twice as high for the quetiapine group. Findings of the present study, along with previous research on the prevalent use of antipsychotic polypharmacy [3
] and its unproven benefits [32
] in the treatment of schizophrenia, suggest that meaningful economic comparisons among atypical antipsychotics can only be achieved by incorporating the cost of antipsychotic polypharmacy in the total medication cost calculations. Findings also suggest the need for additional research to help clarify the underlying reasons for antipsychotic polypharmacy in the treatment of patients with schizophrenia in usual care.
Results of this study need to be evaluated in the context of its limitation. First, this was a nonrandomized, noninterventional, observational study; thus, treatment group selection bias cannot be eliminated despite our use of statistical adjustments – with the propensity score-adjusted bootstrapping method – for various available patient characteristics at the time of medication initiation. Second, this study focused on comparing costs associated with the use of antipsychotics.
The use of other psychotropics may vary among treatment groups and may contribute differentially to the total psychiatric medication costs for different treatment groups. Further studies on the use of all psychotropic medication and its associated costs will provide a better understanding of the costs associated with the use of various atypical antipsychotics in the treatment of schizophrenia. It should be noted that antipsychotics that were on generic such as clozapine or are soon on generic such as risperidone and ziprasidone will be cheaper than their brand names; therefore, the medication costs will be cheaper. In addition, clozapine is an important atypical antipsychotic medication in the treatment of schizophrenia. We decided to only focus on polypharmacy costs associated with the treatment of 3 most commonly used atypical antipsychotics – olanzapine, quetiapine, and risperidone and, at the same time, included any medication costs incurred by clozapine when it was co-prescribed with any of the 3 study medications to ensure that the results and conclusions from this study on the 3 medications are not affected by the exclusion of clozapine as a comparative treatment group. Ziprasidone and aripiprazole were not included in this study due to lack of data for these 2 medications. Ziprasidone was introduced in the United States toward the end of US-SCAP, and aripiprazole was launched after US-SCAP completion.
Finally, this study is unable to explain why there was a greater propensity of olanzapine to be coprescribed with typical antipsychotics and of quetiapine to be coprescribed with atypicals. The US-SCAP did not assess the reasons for clinicians' medication choices, including the reasons for medication initiation or augmentation. Clinicians may prescribe antipsychotics for different reasons to patients with different illness profiles. As a result, the cost advantage of olanzapine over quetiapine may be the result of a biased pattern of prescribing unique to clinicians participating in this protocol. Fully understanding and providing measures for the reasons behind the medication prescription pattern will help better address the potential selection bias associated with an observational study. In this study, we adjusted patient's demographics, hospitalization, illness history, and other observable factors. Unobservable factors may still exist and may create imbalance between the treatment groups.