Researchers at the University of Washington have found that older adults with clinical depression who do not respond to standard treatment might benefit from adding the antipsychotic aripiprazole to their regimen. This finding comes from a study published in the New England Journal of Medicine.
For many patients with clinical depression, medications fail to bring relief. In such cases, clinicians often try another antidepressant to identify one that works, or they consider adding a different class of drugs to the existing treatment to see if a combination yields better results.
Both approaches are approved options for addressing treatment-resistant depression in older adults. A new trial suggests that the strategy of combining a second class of medication with antidepressants may offer greater improvement for some patients.
The trial enrolled 742 individuals aged 60 and above who had depression that did not respond to standard antidepressant therapy. In the initial phase, 619 participants who were already taking antidepressants such as fluoxetine, escitalopram, or sertraline were randomly assigned to three groups.
The first group continued their current antidepressant while adding aripiprazole. Aripiprazole, originally approved for schizophrenia in the United States, has also been used at lower doses as an adjunct to antidepressants for younger patients who did not respond to treatment alone.
The second group continued their antidepressant and added bupropion, sold under Wellbutrin or Zyban. The third group switched entirely to bupropion as their sole antidepressant treatment.
Over a 10-week period, participants had regular contact with clinicians or hospital visits every two weeks to adjust their treatment regimens. By the study’s end, researchers observed that adding aripiprazole led to a more durable improvement in depressive symptoms and a greater uplift in mood for many participants.
Despite these gains, the improvement was modest, with roughly one in three patients experiencing meaningful benefits. The findings underscore the ongoing need for more effective therapies that can help a larger share of older adults with treatment-resistant depression.