Moderators of antidepressant augmentation versus switch in the OPTIMUM randomised controlled trial

Area of Science:

• Geriatric psychiatry
• Pharmacological interventions
• Treatment-resistant depression

Background:

• Older adults with treatment-resistant depression (TRD) often benefit more from treatment augmentation than switching antidepressants.
• Identifying moderators is crucial for personalizing treatment strategies in TRD management.

Purpose of the Study:

• To investigate if age, executive dysfunction, medical burden, anxiety, or prior antidepressant trial count moderates the effectiveness of augmentation versus switching in older adults with TRD.
• To determine factors influencing the differential outcomes between augmentation and switching strategies.

Main Methods:

• A preplanned moderation analysis was conducted on data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) randomized controlled trial (N=742).
• Participants aged 60+ with TRD were randomized to either antidepressant augmentation (aripiprazole, bupropion, or lithium) or switching (bupropion or nortriptyline) for 10 weeks.
• Outcomes measured included symptom improvement (change in MADRS scores) and remission (MADRS ≤ 10).

Main Results:

• The number of previous adequate antidepressant trials significantly moderated depression symptom improvement (P=0.033).
• Augmentation was superior to switching only in older patients with fewer than three prior antidepressant trials.
• No other tested moderators (age, executive dysfunction, medical burden, anxiety) showed significant effects.

Conclusions:

• Treatment augmentation demonstrates superiority over switching in older adults with TRD who have received fewer than three prior antidepressant trials.
• For patients with three or more previous antidepressant trials, alternative intervention strategies should be considered.
• This finding supports personalized treatment approaches in managing treatment-resistant depression in the elderly population.