Aripiprazole or Bupropion Augmentation Versus Switching to Bupropion in Treatment-Resistant Depression: A...

Area of Science:

• Psychiatry and Mental Health
• Pharmacoeconomics
• Clinical Decision Analysis

Background:

• Treatment-resistant depression (TRD) poses significant challenges, necessitating effective augmentation or combination therapies.
• Aripiprazole augmentation (A-ARI) and combination bupropion (C-BUP) are considered for TRD, but carry distinct risk profiles including falls, weight gain, and tardive dyskinesia (TD).
• Switching to bupropion (S-BUP) is another therapeutic option, with varying comparative effectiveness and safety data.

Purpose of the Study:

• To conduct a risk-benefit analysis comparing C-BUP and A-ARI against S-BUP for TRD treatment.
• To evaluate the enhanced effectiveness of these strategies against their associated risks, such as falls, weight gain, and TD.
• To inform clinical guidelines and shared decision-making in TRD management.

Main Methods:

• A health-state transition model was employed to simulate lifetime quality-adjusted life-years (QALYs) over one year of treatment.
• The model tracked key health states including depression remission, falls, weight gain, and TD, stratified by age and baseline BMI.
• Data from VAST-D and OPTIMUM trials, along with other literature, informed the model parameters. QALYs were converted to depression-free day-equivalents (DFDs).

Main Results:

• In adults aged 18-64, C-BUP demonstrated a net benefit of 20.7 DFDs over S-BUP, indicating approximately 3 weeks faster symptom remission.
• For older adults, C-BUP's benefit over S-BUP was partially offset by fall risks, particularly in those aged 85+.
• A-ARI yielded fewer benefits (8.0 DFDs) compared to S-BUP, with benefits diminishing to -22.8 DFDs in overweight individuals due to TD and metabolic harms.

Conclusions:

• Combination bupropion (C-BUP) presented a superior balance of efficacy and tolerability for treating TRD in adults under 85 years compared to S-BUP and A-ARI.
• Aripiprazole augmentation (A-ARI) was least preferred in overweight adults due to adverse metabolic effects.
• The findings support C-BUP as a preferred option in most TRD patient subgroups, guiding clinical practice and patient-provider discussions.