A new meta-analysis found that certain antidepressants worked better on average than Prozac at helping people with depression feel better and stick with their treatment over the long term.
The analysis looked at 21 different drugs across 115 studies to identify which drugs were most likely to help patients who planned to use antidepressants for more than three months. The study authors compared each drug to Prozac, also known as fluoxetine, because it’s a well-known drug that has been commonly prescribed, researchers said.
While most of the antidepressants were comparable in terms of how well they worked or how long patients stayed on them, there were some subtle differences. People taking escitalopram (Lexapro), duloxetine (Cymbalta) or agomelatine (Thymanax), were more likely than those taking fluoxetine to see their symptoms improve and stay better.
And there were two medications that performed worse than multiple other antidepressants: bupropion (known as Wellbutrin or Zyban) and reboxetine (Edronax).
Depression is one of the most common mental health disorders in the world and many people end up taking antidepressants for years. But there has been little research comparing the effectiveness of different antidepressants beyond the length of a typical clinical trial, which is usually around eight weeks.
The study, which was published on Tuesday in The Lancet Psychiatry, analyzed both published and unpublished studies that followed participants with major depressive disorder for more than 12 weeks, and one as long as two years. They looked at whether the subjects had a “sustained response” to each drug, meaning an improvement in symptoms that lasted until the trial ended. The researchers also looked at whether the study subjects stopped taking the drug for any reason, assuming that those people did so because their symptoms had not improved.
The new data may benefit people who want to start an antidepressant and wish to narrow down the potential options, said Dr. Henricus G. Ruhé, a professor of psychiatry at Radboud University Medical Center in the Netherlands and one of the lead authors of the study.
But it may be less helpful for people who are already using an antidepressant that is working well for them. “Why change a winning team?” he asked.
The choice to take a specific antidepressant depends on multiple factors including a patient’s symptoms and medical history as well as the drug’s tolerability and effectiveness, Dr. Ruhé cautioned.
Other clinicians who were not involved in the study agreed.
Dr. Olusola Ajilore, a member of the American Psychiatric Association’s council on research, emphasized the importance of assessing how well the drug works for each individual. For instance, are the side effects “a nonstarter, or something they’re willing to tolerate?” he asked.
A patient’s depressive symptoms will also guide prescribers, he added. “If somebody is sleeping too much, you’re not going to give them something that’s going to be sedating,” he said.
In addition to the drug comparisons, the study authors also performed a separate analysis of people whose symptoms had already improved on an antidepressant. In those cases, about 62 percent of patients who kept taking it for six months or more maintained improvement, compared with around 45 percent of those switched to a placebo, suggesting that, overall, taking medication can help keep depression at bay.
One of the biggest limitations of the study was that many of the available clinical trials were about six months in duration, and there was a dearth of data beyond one year of follow-up. This is because it is expensive to conduct lengthy clinical trials and years-long follow-up is not required when seeking regulatory approval for an antidepressant, Dr. Ruhé said.
But in practice, it’s common for people to take these drugs for much longer. A quarter of people who have taken antidepressants did so for a decade or more, according to the Centers for Disease Control and Prevention.
In addition, the paper noted that about half of the studies were at “high risk” of bias, which makes the drug comparisons less certain. Finally the researchers could not differentiate by gender or ethnicity, Dr. Ruhé said.
Dr. Gerard Sanacora, director of the Yale Depression Research Program, who was not involved in the study, said that the meta-analysis, while well-designed and important, doesn’t negate the need for real-world data.
In the end, each patient should choose the treatment that’s best for them, whether that’s an antidepressant, therapy or a combination of different approaches, Dr. Sanacora said.
“The decision always should be made on an individual patient basis,” he added.
