Home » Depression » Many Antidepressants May Be Ineffective, Even Harmful, for Teens
Many Antidepressants May Be Ineffective, Even Harmful, for Teens

Many Antidepressants May Be Ineffective, Even Harmful, for Teens

Nearly all antidepressant drugs are considered ineffective for children and teens with major depressive disorder, according to the most comprehensive study ever conducted on this topic, published in The Lancet.

In fact, some of these drugs are considered entirely unsafe for teens, further raising the risk of depression and suicide attempts.

Out of the 14 antidepressant drugs that were studied, the findings indicate that only one — fluoxetine (Prozac) — was more effective than placebo. The drug with the greatest risk for causing serious harm to teens was venlafaxine (Effexor) which was tied to an increased risk of suicidal thoughts and attempts compared with placebo and five other antidepressants.

Even more alarming is that the true effectiveness and dangers of these drugs still remain unclear because of the small number and poor design of clinical trials assessing these antidepressants, say the authors. One of the most disturbing problems is the selective reporting of the findings of published trials and clinical studies.

In fact, the findings show that 22 (65 percent) of these trials were funded by pharmaceutical companies. Ten (29 percent) trials were rated as high risk of bias, 20 (59 percent) as moderate, and four (12 percent) as low.

“Without access to individual-level data it is difficult to get accurate effect estimates and we can’t be completely confident about the accuracy of the information contained in published and unpublished trials. It has been widely argued that there needs to be a transformation of existing scientific culture to one where responsible data sharing should be the norm,” said lead author Dr. Andrea Cipriani at the University of Oxford in the U/K.

Major depressive disorder affects approximately three percent of children aged six to 12 years and about six percent of teenagers aged 13 to 18 years.

Talk therapy is suggested as the first-line treatment for young people with depression. In fact, in 2004 the US Food and Drug Administration (FDA) put out a black box warning against the use of antidepressants in young people up to 24 years because of concern about increased risk of suicidality.

Still, the use of antidepressants among young people has slowly increased between 2005 and 2012. For example, in the U.S., the proportion of young people aged zero to 19 years taking antidepressants increased from 1.3 percent to 1.6 percent, and in the U.K. from 0.7 percent to 1.1 percent. Sertraline (Zoloft) is the most widely prescribed antidepressant in the U.S. and fluoxetine (Prozac) is the most common in the U.K.

For the review, the researchers combed through a network meta-analysis of all published and unpublished randomized trials comparing the effects of 14 antidepressants in young people with major depression up to the end of May 2015.

They rated these drugs for efficacy (change in depressive symptoms and response to treatment), tolerability (discontinuation due to adverse events), acceptability (discontinuation due to any cause), and associated serious harms (ie, suicidal thoughts and attempts).

An analysis of 34 trials involving 5,260 participants (average age nine to 18 years) showed that the benefits outweighed the risks in terms of efficacy and tolerability only for fluoxetine.

Nortriptyline (Pamelor) was less effective than seven other antidepressants and placebo. Imipramine (Tofranil), venlafaxine (Effexor), and duloxetine (Cymbalta) had the worst profile of tolerability, leading to significantly more discontinuations than placebo. Venlafaxine (Effexor) was linked with an increased risk of engaging in suicidal thoughts or attempts compared with placebo and five other antidepressants.

The researchers caution that due to the lack of reliable data, it was not possible to comprehensively assess the risk of suicidality for all drugs.

“The balance of risks and benefits of antidepressants for the treatment of major depression does not seem to offer a clear advantage in children and teenagers, with probably only the exception of fluoxetine. We recommend that children and adolescents taking antidepressants should be monitored closely, regardless of the antidepressant chosen, particularly at the beginning of treatment,” said co-author Dr. Peng Xie from the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Writing in a linked Comment, Dr. Jon Jureidini at the University of Adelaide in Australia questions how many more suicidal events might have been revealed had individual patient-data been available.

“[For example], in four trials of paroxetine versus placebo, only 13 (3 percent) of 413 events were reported in the paroxetine group; this seems implausible when individual patient-level data reanalysis of just one of those studies found ten events in only 93 patients given paroxetine (10.8 percent),” said Jureidini.

“The effect of misreporting is that antidepressants, possibly including fluoxetine, are likely to be more dangerous and less effective treatments than has been previously recognized, so there is little reason to think that any antidepressant is better than nothing for young people…

“Patients who take part in randomized controlled trials have a right to expect that maximum benefit will come from the data they generate.”

Source: The Lancet


Many Antidepressants May Be Ineffective, Even Harmful, for Teens

Traci Pedersen

Traci Pedersen is a professional writer with over a decade of experience. Her work consists of writing for both print and online publishers in a variety of genres including science chapter books, college and career articles, and elementary school curriculum.

APA Reference
Pedersen, T. (2018). Many Antidepressants May Be Ineffective, Even Harmful, for Teens. Psych Central. Retrieved on December 2, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 13 Jun 2016)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
Published on Psych All rights reserved.