On the debate over the effectiveness of antidepressants versus placebos, Yale scientists have weighed in on the side of the antidepressants.

Researchers at the Yale School of Medicine have published a statistical analysis showing that patients receiving antidepressant drugs recover from depression better than patients on a placebo treatment. The study, published in Archives of General Psychiatry in December, analyzed clinical trials involving a total of 2,515 patients with major depression who were either given an antidepressant drug or a placebo. One of the leaders of the study, John Krystal MED ’84, chair of the department of psychiatry at the Yale School of Medicine, said that the research contradicted earlier research claiming that placebos were just as effective as antidepressants.

“Antidepressant response seemed to fall into two categories: responders and non-responders,” Krystal said, with only the former group improving as a result of the medication. By contrast, the other 25 percent of the patients, the “non-responders,” responded worse to the antidepressants than patients responded to the placebos.

Krystal said his team had not expected that some patients would be worse off from medications than patients on placebo. This effect might have been caused by the stressful nature of clinical studies or the progressive accumulation of different medications taken “like barnacles on a ship,” Krystal said.

Krystal said that overall, patients benefitted from the antidepressant drugs, and any negative effects could be dealt with by improving the communication between doctors and patients. He said that a better understanding of when to lessen drug prescriptions for patients who did not respond positively to them was one possible application of this research.

Steven Julious, who conducts research in medical statistics at the University of Sheffield in the United Kingdom, said that the condition of patients on placebos may improve by virtue of the attention doctors give them during clinical trials.

“When you’re in a clinical trial, you get better treatment,” Julious said. “When you’re on a placebo, you still get treatment.”

Krystal said the Yale study was more accurate than traditional statistical methods because it took into account “built-in biases,” such as variations in patient response times to different treatments.

Ralitza Gueorguieva, a researcher in the Yale School of Public Health, led the statistical analysis by using a growth-mixture model, which uses the natural response time to antidepressant drugs to better understand the comparative response time for drugs compared to placebos.

“The benefits of antidepressants take several weeks to take effect. Growth-mixture modeling allowed us to take this into account,” Krystal said.

Like the Yale study, Julious conducted a statistical analysis of data from clinical trails to analyze the potency of antidepressant treatments. Julious said his findings agreed with previous research that antidepressants are effective but can lead to suicide risks in adolescent patients.

Julious said science might never find “a definitive answer” to the source of the effectiveness of antidepressants because of the complexity of the disease, but that these studies are still valuable to conduct.

“This is a part of medical research that can never be concluded,” Julious said.

The Yale research study was accepted for publication on July 11, 2011.