This study compared total medical costs and utilization among patients with depression who received adjunctive therapy with one of three indicated atypical antipsychotics: aripiprazole, olanzapine, or quetiapine. Based on the results of this study, patients who were treated with aripiprazole had significantly lower total medical costs compared to patients treated with olanzapine or quetiapine. To further understand the differences across the cohorts, total medical costs were divided into inpatient and outpatient costs. Results showed that inpatient costs were a significant component of the total medical costs for olanzapine and quetiapine cohorts and were significantly higher compared to inpatient costs for patients on aripiprazole. Consistent with this, it was found that the aripiprazole cohort had significantly lower hospitalizations and ER visits compared to both olanzapine and quetiapine.
Recently, Jing et al carried out a study to evaluate healthcare costs and utilization in patients with depression receiving atypical antipsychotics as adjunctive therapy.16
While the two studies would appear similar, the current study had a longer follow-up period (12 months vs 6 months), was conducted in a different commercial population and used more recent data. Furthermore, while the Jing et al study focused solely on patients who were newly initiated with atypical antipsychotics as a first-line augmentation strategy, the current study examined all patients newly initiated with atypical antipsychotics, irrespective of whether the atypical antipsychotic was a first-line augmentation strategy. Despite these differences, the results were consistent, demonstrating that total medical costs were significantly lower for aripiprazole-treated patients than olanzapine- and quetiapine-treated patients. In the study by Jing et al, adjusted 6-month total medical costs (in 2009 dollars) were $6,062 for olanzapine and $7,298 for quetiapine, compared to $3,986 for aripiprazole (P
= 0.02 and P
< 0.01 respectively). The current study also revealed that 12-month total medical costs (in 2010 dollars), were significantly higher for patients in the olanzapine ($14,275), and quetiapine ($12,998) cohorts compared to patients in the aripiprazole cohort ($9,801; P
< 0.05 for all comparisons with aripiprazole).16
While the results were consistent between the two studies, the Jing et al study had slightly lower monthly total medical costs, which may be due to the fact that the patients in that study had less disease severity than patients in the current study. This discrepancy in disease severity across the two studies is likely because the current study focused on all patients newly initiated with atypical antipsychotics regardless of line of therapy, resulting in a population with greater disease severity compared to the Jing et al population. Results for utilization outcomes were also consistent, as in both studies the adjusted relative risk of hospitalization for quetiapine-treated patients was significantly higher compared to aripiprazole-treated patients. The adjusted risk for hospitalization was numerically higher for the olanzapine cohort compared to the aripiprazole cohort in the Jing et al study, but it did not reach statistical significance. Consistent with this, Jing et al demonstrated that ER visits mirrored total hospitalization results, with significant differences for the quetiapine cohort and numerically higher values for the olanzapine cohort that did not reach significance compared to the aripiprazole cohort.16
These differences may be attributable to differences in patient populations or differences in follow-up time. Overall, however, the trends between the studies were consistent.
Other researchers have attempted to quantify and compare the effectiveness of atypical antipsychotics in MDD. A decision analytic model was constructed by Taneja et al to evaluate the cost-effectiveness of indicated atypical antipsychotics in patients with MDD.24
The model inputs were based on clinical trial data and were used to calculate the cost per responder. Patients receiving aripiprazole had the lowest cost per additional responder ($3,447), followed by olanzapine/fluoxetine ($3,993), quetiapine 300 mg/day ($6,000), and quetiapine 150 mg/day ($8,725).24
It should be noted that the results were based on inputs from clinical trial data, and on specific FDA-approved dosing ranges for each agent, so are less reflective of the real world than the current study.
The reason for the differences observed in the current study is not known. It was found that real-world dosing differed among the patient populations, as significantly more patients receiving aripiprazole were dosed within the FDA-approved therapeutic range than the other two cohorts. This discrepancy in dosing within therapeutic range for atypical antipsychotics has been noted in other studies16
and while it is not clear what the total impact of this is on the results of the current study, it is reasonable to speculate that patients dosed within the appropriate range may be more likely to experience better outcomes.
It is also possible that differential pharmacokinetic properties of the atypical antipsychotics may have impacted the outcomes. Broder et al evaluated hospitalization rates and adherence among patients treated with atypical antipsychotics based on agents with short half-lives compared to agents with longer half-lives.26
Agents with longer half-lives (risperidone, olanzapine, and aripiprazole) were less likely to incur a hospitalization or ER visit for mental disorders for a given level of adherence than patients taking an agent with a shorter half-life (quetiapine or ziprasidone).26
Since aripiprazole has a long half-life (approximately 75 hours) compared to both olanzapine (37 hours) and quetiapine (6 hours), it may help explain the lower total medical costs and utilization for the aripiprazole patients in the current study, given the impact of half-life on effectiveness, as seen in the Broder et al study.21
As this was a retrospective database study, there was no randomization. Baseline characteristics varied across the cohorts and may have impacted the results. While patients in the aripiprazole cohort had significantly lower PDG scores than patients receiving quetiapine, and significantly lower CCI scores compared to olanzapine and quetiapine, aripiprazole patients had a higher MGH-AD score. Additionally, the aripiprazole cohort had a higher proportion of patients on a preindex mood stabilizer or stimulant, and were more likely to visit a psychiatrist and have a diagnosis of MDD based on an ICD-9 code of 296.2x or 296.3x relative to the other cohorts. By 6 months and with a continuing trend at 12 months, a significantly higher proportion of patients were receiving a dose within the therapeutic range. A multivariate approach was taken in an effort to minimize the bias associated with nonrandomization. Given the nature of claims-data research, information on baseline clinical severity of the patients was not readily ascertainable; however, proxies for disease severity based on available data were created and used in a multivariate framework to control for mitigating circumstances surrounding MDD and other comorbidities. This study considered only total medical costs, and did not incorporate pharmacy (ie, medication) costs into the analysis. Current relative pharmacy costs likely differ from pharmacy costs when this study was conducted due to the recent introduction of generic olanzapine and quetiapine; therefore, for this analysis we focused on the relative total medical costs of patients using each medication, which will likely remain consistent between the study period and the present day. Lastly, the main analysis was conducted on an intent-to-treat basis. This methodology has the potential to introduce some bias, since patients could have discontinued or switched atypical antipsychotic therapy during the study period. However, sensitivity analysis showed that the trends from the main analysis were also present at 6 months.