Starting depressed adolescents on placebo can achieve just as effective an outcome in a controlled clinical trial as drug therapy from the outset, a US analysis has found.

Published by The American Journal of Psychiatry, the study is the first to address the ethical implications of delaying effective treatment for adolescents in research, said lead author Dr Betsy Kennard, associate professor of psychiatry at the University of Texas (UT) Southwestern in Dallas. “Without placebo groups, it’s difficult to determine the efficacy of a treatment,” she noted. “Now we’ve shown scientifically that these trials are safe and effective.”

Kennard performed a secondary analysis in the Treatment for Adolescents with Depression Study (TADS), led by Dr John March of Duke University Medical Center in Durham, North Carolina. This involved 439 adolescents, aged 12 to 17 years, with moderate to severe major depressive disorder, who were treated at 13 sites across the US – around 50 of them at UT Southwestern.

The main study found that 12 weeks of treatment with a combination of antidepressant medication and cognitive behavioural therapy was more effective than cognitive behavioural therapy alone or placebo treatment. Kennard looked at what happened to the adolescents in the placebo group.

For 12 weeks these participants received education, sessions with a psychiatrist, supportive care and clinical management, just as the active treatment groups did. They were also given a placebo. Around 35% of the placebo group improved on this basis alone, Kennard reported.

“Placebo can be misconstrued as if it’s a bad thing,” she commented. “These adolescents received quite a bit of clinical care, and for some of them, that was enough to help them get well. If at any time a child started to do worse, we would change their treatment no matter what group they were in,”

After 12 weeks, most of the 65% of participants who did not initially respond to placebo subsequently chose to receive antidepressant medication either alone or in combination with cognitive behavioural therapy. At the end of nine months, the researchers found that adolescents first given placebo treatment for 12 weeks and then active treatment had a response rate of 82%, compared with an 83% response for participants who received active treatment for the whole period.

The study also examined related effects such as risk of harm, suicidal events, use of outside treatment and drop-out rates to see if the placebo group fared worse on these parameters.

“In terms of every possible way that we could look at the patients, adolescents first given placebo treatment performed as well or had as positive a response as those given other treatment for the entire 36 weeks,” Kennard said. “So it’s OK to consider participating in research, even in a controlled study, because in a well-conducted trial, you receive a considerable amount of clinical care, and there is quite a bit of oversight.”