Comparing Cost Effectiveness of Aripiprazole Augmentation with Other “Next-Step” Depression Treatment Strategies

Background: Atypical antipsychotic drugs are widely prescribed for major depressive disorder as a second-line therapy to augment antidepressant use despite little evidence regarding their comparative cost effectiveness. Atypical antipsychotics such as aripiprazole had much higher prices when first introduced, but recent generic equivalents have substantially narrowed price differentials between them and older antidepressant drugs. We used data from a randomized clinical trial to compare the cost effectiveness of augmenting standard antidepressant therapy with aripiprazole compared to another augmentation agent, bupropion, and to switching to bupropion over a 12-week acute treatment phase.

Methods: The cost-effectiveness analysis (CEA) was conducted as part of the Veterans Affairs (VA) augmentation and switching treatments for improving depression outcomes (VAST-D) trial in which 35 participating VA medical centers enrolled 1,522 patients who had failed prior pharmacotherapy. Remission from depression and quality-adjusted life years were estimated from trial data collected at baseline and 12 weeks after randomization. Health care costs from 2015 were obtained from VA administrative data. We compared the cost effectiveness of the 3 strategies by estimating the costs per remission with 12 weeks as the time horizon and the health care sector as the primary perspective. We calculated the incremental cost-effectiveness ratio (ICER) using the difference in costs between each treatment strategy versus the other divided by the differences in remission rates at 12 weeks. We calculated 95% confidence intervals around the ICER’s using bootstrap methods.

Results: The mean age of participants enrolled in the trial was 54 years, and participants were predominantly male. The rate of remission at 12 weeks was highest for the aripiprazole augmentation arm (29%), followed by bupropion augmentation (27%), and lowest for bupropion monotherapy (22%). Mean mental health care costs which included the costs of outpatient mental health care visits, inpatient psychiatric stays, and the study drugs did not differ significantly between the groups. The incremental cost effectiveness ratio (ICER) comparing costs per remission was lowest for the bupropion augmentation group relative to the bupropion monotherapy group at -$640/remission. The ICER for the aripiprazole augmentation versus bupropion monotherapy group was $1,074/remission (95% CI =47-5022) with 97.9% of the observations in upper-right quadrant, indicating greater costs and benefits associated with aripiprazole. The ICER for aripiprazole augmentation versus bupropion augmentation was $5,094/remission (95% CI =-34027-32774) with 75.6% of the observations in the upper right quadrant. We did not find any significant differences in mental health care costs, quality-adjusted life years, employment, and other work and social adjustment outcomes between treatment groups during follow up.

Conclusion: In treatment of non-responsive depression, augmentation with either aripiprazole or bupropion increased costs as compared to switching to a new antidepressant, but these costs were justified by higher remission indicating that both augmentation approaches were cost-effective compared to switching antidepressants.