A new review in The Lancet Psychiatry compared how well different antidepressants maintain improvements in depression over the long term. Researchers analyzed 115 randomized controlled trials involving more than 30,000 people. Their main analysis combined 35 trials that directly compared one antidepressant with another.
The study found that escitalopram (Lexapro), duloxetine (Cymbalta), and agomelatine (Valdoxan) were associated with greater likelihood of sustained response than fluoxetine (Prozac). People taking escitalopram or duloxetine were also less likely to drop out of trials than those taking fluoxetine.
However, the findings carry limitations. More than half of the studies included in the main analysis had a high risk of bias, meaning some differences between antidepressants may reflect study limitations rather than genuine differences in the medicines themselves. Some medicines were supported by very few studies. The trials directly comparing antidepressants typically followed participants for about six months after they started medication. Only six trials followed people longer than six months, leaving questions about how effectiveness compares over longer periods.
The results reflect average outcomes across groups. They cannot predict which antidepressant will work best for any individual person, since people respond differently to antidepressants and tolerate them differently. The researchers measured acceptability using trial drop-out rates, but this does not capture the full experience of taking these medicines, including side effects and withdrawal symptoms when discontinuing.