We found that among depressed teens who failed a previous adequate course of SSRI medication treatment, CBT combined with medication switch achieved 8.3 more DFDs and 11.0 more DIDs across a 24-week treatment period. Combination therapy was significantly more expensive than medication switch alone. In the base case analysis, the mean ICER comparing combination treatment with medication switch alone was $188 per DFD and $78 948 per DFD-QALY. The CEAC analyses suggest that combination therapy has a 61% probability of being more cost-effective than medication alone if a decision maker is willing to pay $100 000 per QALY.
Interpretation of cost-effectiveness depends on a decision maker’s willingness to pay for an additional unit of clinical outcome (eg, QALY). There is no official standard for cost-effectiveness in the United States,29
and there is ongoing discussion about the appropriateness and amount of a standard.40–42
One frequently cited criterion is that if an intervention has an incremental cost per QALY of $50 000 or less, it is a reasonable value compared with many of the medical treatments currently covered under typical insurance packages.40,42
Several experts have recently argued that this criterion is too conservative, suggesting that more appropriate criteria might be in the range of $109 000 to $297 000.42
Results of the present base case analysis and all sensitivity analyses fall below the latter-range, but the base case analysis is higher than the $50 000-per-QALY level.
In the literature on the cost-effectiveness of adult depression treatments, researchers have commonly reported incremental cost-effectiveness results using a cost-per-DFD metric. Comparing interpersonal psychotherapy with usual care for depression treatment, Lave and colleagues14
reported average cost-effectiveness for 2 types of depression treatment at $13 and $18 per DFD for direct costs only and $15 and $25 per DFD for costs including patient time and transportation. Simon and colleagues43
reported average cost-effectiveness for systematic depression treatment for high users of general medical care of approximately $41 per DFD for direct costs and $52 per DFD including patient time cost. Another study24
comparing cost-effectiveness of collaborative care for persistent depression reported cost per DFD of $21 to $35 depending on the types of costs included. Finally, a review44
of studies comparing cost-effectiveness of enhanced primary care for depression reported cost per DFD of $13 to $24 depending on the types of costs included. The present base case result ($188 per DFD) and most of the additional analyses are substantially higher than these results.
We also found that the cost per clinical outcome was much more favorable for some subgroups. For teens with no history of abuse and youth with low hopelessness levels, the ICERs for combined therapy compared with medication switch alone were always $50 000 per QALY or less; the CEAC analysis found that there was a 90% probability that RX + CBT is cost-effective compared with RX for low levels of hopelessness at a value of $65 000 per QALY and a 90% probability that RX + CBT is cost-effective compared with RX for youth with no history of abuse at a value of $105 000 per QALY. For youth with comorbid conditions, we found somewhat more favorable, albeit modest, cost-effectiveness results compared with the base case.
The present findings add to the growing literature about the efficiency of providing combined therapy to youth with depression. Domino and colleagues2,4
found that the incremental cost-effectiveness of combined treatment compared with medication alone was $458 818 per QALY at 12 weeks, concluding that combination therapy was not more cost-effective at 12 weeks; however, in a longer-term analysis, they found that combination therapy is likely to be cost-effective compared with medication alone at 36 weeks. Byford and colleagues45
found that combination CBT and medication was unlikely to be more cost-effective compared with medication alone in the UK health system in the short-term. The present results are somewhat more favorable than those of previous studies, with lower estimated incremental costs per QALY that have a reasonably good probability of being cost-effective for some subgroups.
The results of this analysis also contribute to the understanding of the efficiency of combined therapy for youth depression because of differences in the TORDIA population. Some previous trials have been limited to youth in an initial episode of depression2
or have not included youth who failed a previous trial of medication,5
whereas the TORDIA study included youth with chronic depression who failed previous adequate medication treatment. In the present base case analysis, we used a preference weight to convert DFDs and QALYs used in multiple previous studies of depression treatment.2,14,15
Given the high-risk population in the TORDIA study, use of a preference weight for more severe depression may be more appropriate. The sensitivity analyses indicate that when we used a preference weight for severe depression and DFD-QALY as the outcome, combined therapy was likely to be cost-effective compared with medication assuming that a decision maker is willing and able to pay $100 000 per QALY.
The results of this study should be interpreted in light of several limitations. First, we did not include productivity costs for youth associated with depression. A growing body of research indicates that adult depression is associated with a significant reduction in workplace outcomes.46,47
Other recent research has found that depression in adolescence is associated with a variety of negative educational outcomes48,49
and reduced earnings in adulthood.48,50
Together, these findings suggest that youth depression may reduce human capital development. For example, approximately 4% of the youth in the TORDIA trial were hospitalized during the 24-week study, with an average stay of 12 days. Therefore, a subgroup with treatment-resistant depression may be missing a significant number of school days due to hospitalization, and this does not include school days missed when the youth were not hospitalized or had reduced productivity in school.
Other family costs may also be important.1
For example, although we included some travel and visit time costs for parents of hospitalized youth while the youth was in the hospital, families likely spent considerable additional time related to the hospitalizations, such as time spent on insurance-related issues and coordinating and planning for care for the youth once they were released from the hospital. These costs were not included in this analysis.
There are 2 other limitations related to the methods. The TORDIA trial did not include a preference-based measure of health-related quality of life, which would have allowed direct measurement of the impact of the interventions on youth QALYs. Therefore, we had to rely on indirect methods to calculate QALYs. We followed an established method for translating DFDs into QALYs,2,4,14,15
but we had to use preference weights reported in the literature for adults with depression because no empirical ones exist for teens. Adult weights may not accurately represent the impact of depression on teen quality of life.51
The preference weights we used measure only the decrease in health-related quality of life associated with depression; changes in health-related quality of life associated with comorbidities were not captured. Finally, we used nationally representative unit costs for nonprotocol services that were developed for another study of teen depression, which may not accurately represent the actual unit costs at all 6 study sites.
In conclusion, many youth do not respond to a first course of treatment for major depression, yet the clinical outcomes and costs for persistent depression are significant. If a decision maker is willing and able to pay $100 000 per QALY, combined therapy has a moderate probability of being cost-effective compared with medication switch alone for all youth with treatment-resistant depression across 24 weeks of treatment. In addition, we find that combined therapy is much more likely to be cost-effective compared with medication switch alone for some subgroups of youth with treatment-resistant depression. At minimum, expansion of the use of combined therapy for targeted subgroups of youth with treatment-resistant depression is warranted.