November 11, 2026
Thom Carroll/PhillyVoice
New research suggests that some antidepressants do a better job than others at offering sustained relief.
With as many as 20% of U.S. adults reporting experiences with depression, finding an effective treatment is critical. But landing on an antidepressant or combination of medications that helps resolve persistent feelings of sadness and hopelessness has been a process of trial and error for many people.
New research suggests that process may become more precise for people seeking medication for depression. A meta-analysis of 115 studies, published Tuesday in the Lancet Psychiatry, has identified that certain antidepressants appear to give more sustained relief than others.
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The analysis found that escitalopram (Lexapro) and duloxetine (Cymbalta) were more effective long term than fluoxetine (Prozac). The research also showed that bupropion (Wellbutrin) and reboxetine (Edronax) seemed to offer less enduring relief than many other of the antidepressants. The analysis involved more than 30,000 people and 21 medications.
The analysis included studies that lasted from 12 weeks to two years. The researchers used fluoxetine – one of the most commonly prescribed antidepressants – as a metric for comparing the other medications.
The study might help people who are looking to start an antidepressant make a more informed decision about which one to take, Dr. Henricus Ruhé, one of the study's lead authors and a professor of psychiatry at Radboud University Medical Center in the Netherlands, told the New York Times. But the research may not have much impact for people who have found an effective antidepressant or combination of medications.
"Why change a winning team?" Ruhé asked.
Depression, also called major depression or clinical depression, can afflict people with a wide range of symptoms, not just sadness and hopelessness. Other symptoms include irritability, fatigue, appetite changes and loss of pleasure or interest in activities. Feelings of worthlessness and guilt, slowed thinking and movement, suicidal thoughts and physical pain also may appear, the Mayo Clinic says.
It is important to treat depression – just as it is important to treat any other disease – because it is hard to endure, impacts relationships and can get worse if left untreated. Depression can lead to other health complications, such as obesity and substance use disorders. Some people with depression at risk of suicide.
Effective treatment may involve a combination of medication, therapy, exercise and lifestyle changes.
The new research found that people who had remained on antidepressants for six months or longer experienced more sustained relief than people who discontinued medication or switched to a placebo.
But sometimes people stop taking antidepressants due to side effects, which may include weight gain, fatigue, sleep changes and sexual dysfunction.
A prior meta-analysis of more than 150 studies involving 30 antidepressants tracked the medications' effects on blood pressure, heart rate and weight. The researchers found an association between fluoxetine and elevated blood pressure and venlafaxine and increased heart rate.
Fluoxetine, sertraline (Zoloft) and bupropion (Wellbutrin) were associated with weight loss. People on the less common mirtazapine (Remeron) experienced weight gain.
Finding the most effective antidepressant with the least side effects comes down to providers working with individual patients, health experts say.
"As a prescriber, you consider the balance between a medication's benefits and side effects. That balance differs from person to person," Ruhé said in a news release. "Therefore, the choice of medication may vary for each individual patient. Nevertheless, our study can help inform the decisions that prescribers and patients make together: if you start an antidepressant, choose one that not only helps you to get well, but also keeps you well."
