Clinical Summary: Aripiprazole or Bupropion Augmentation Versus Switching to Bupropion in Treatment-Resistant Depression: A Risk-Benefit Analysis
Patients with treatment-resistant depression often face a tradeoff between greater symptom benefit and meaningful long-term harms when clinicians choose between switching to bupropion, adding bupropion, or augmenting with aripiprazole. This analysis matters because it integrates remission benefits with falls, weight gain, and tardive dyskinesia to show how age and baseline BMI can change which option offers the best overall health benefit.
Key Findings
- In the base case, C-BUP was preferred over S-BUP for all subgroups, and S-BUP was not the preferred treatment for any subgroup.
- The one subgroup in which A-ARI was preferred over C-BUP was adults aged 85–89 years of nonelevated weight, for whom A-ARI offered 3.0 more DFDs than C-BUP and 10.9 more DFDs than S-BUP.
- In adults under 65 years, A-ARI offered 27.3 additional gross DFDs of depression efficacy compared to S-BUP, but the harms from TD offset 56%–81% of that depression benefit.
- Among patients who were overweight at baseline, weight-related side effects of A-ARI relative to S-BUP were 95%–131% as large as the depression benefit of A-ARI over S-BUP, and S-BUP was preferred in patients who were overweight at baseline.
- Treatment selection was least stable in the oldest subgroup: in adults aged 85–89 years of nonelevated weight, A-ARI, C-BUP, and S-BUP were favored in 58.8%, 36.0%, and 5.2% of probabilistic sensitivity analysis runs, respectively; in adults aged 85–89 years of elevated BMI, C-BUP was preferred in 70.0% of runs, S-BUP in 15.8% of runs, and A-ARI in 14.2% of runs.
For most adults with treatment-resistant depression, bupropion augmentation offered the best overall risk-benefit balance, while aripiprazole augmentation was the least favorable option in patients with elevated baseline BMI. The main exception was adults aged 85–89 years of nonelevated weight, in whom aripiprazole ranked highest because falls weighed more heavily against C-BUP.
Practice Implications
- Consider baseline BMI explicitly before choosing aripiprazole augmentation; in patients who were overweight at baseline, S-BUP was preferred over A-ARI once weight gain and TD were included.
- When discussing aripiprazole, frame the efficacy gain against long-term adverse effects: in adults under 65 years, the modeled efficacy advantage over S-BUP was 27.3 DFDs, but TD alone offset 56%–81% of that benefit.
- In older adults, weigh fall risk more heavily when considering C-BUP, especially in the aged 85–89 years cohort, where uncertainty in treatment ranking was greatest and A-ARI was favored in 58.8% of probabilistic sensitivity analysis runs for those of nonelevated weight.
- Use shared decision-making when choosing among augmentation and switching strategies, because the preferred option changed by subgroup and sensitivity analyses showed the oldest patients had the greatest uncertainty.
