When Your First Antidepressant Doesn’t Help, What’s Next?

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Some people with depression don’t achieve remission with the first antidepressant they try. Most of them end up switching to another medication or a combination of medications. Finding the best treatment remains partly a process of trial and error. A study published in JAMA in 2017 offered evidence for one particular approach.

Patients with major depression at 35 Veterans Health Administration medical centers who did not respond to at least one antidepressant were randomly assigned to one of three groups: one in which participants’ current antidepressant was replaced with bupropion (Wellbutrin), a second in which the current antidepressant was augmented with bupropion, or a third in which the current antidepressant was replaced with aripiprazole (Abilify). After 12 weeks, 1,296 individuals had completed the treatment phase.

In the group that switched to bupropion, slightly more than 22 percent (114 individuals) experienced remission. Almost 27 percent (136 individuals) of those who augmented their current treatment with bupropion went into remission. Of those who augmented their antidepressant with aripiprazole, nearly 29 percent (146 participants) experienced remission.

Finding the best treatment means weighing both benefits and unwanted side effects. In this study, bupropion was associated with more reports of anxiety, and aripiprazole with sleepiness, weight gain, and a movement disorder called akathisia. If your medication isn’t working, talk with your doctor to find another option.