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Hi! David Rosenberg here for the Psychopharmacology Institute; we are excited to introduce something new called CAP Smart Takes or Child and Adolescent Psychiatry Smart Takes.
So, what exactly is a CAP Smart Take? First and foremost, they are short, quick, and clinically relevant to all of you who treat various childhood-onset psychiatric disorders, from childhood and adolescent psychosis to OCD, eating disorders, bipolar disorder, depression, anxiety, autism spectrum disorder, and many more. I hope I am not leaving any of your favorites out.
The goal is not to be encyclopedic but short and to the point. CAP Smart Takes will give you the big picture and key points that are most clinically relevant, including newer alternative approaches for a particular childhood disorder. We will not go into a detailed methodology; this is not an ivory tower with armchair theories.
We will drill down on what can immediately inform your practice and hopefully provide some innovative strategies to improve the outcome of the children and families we serve. We know that children and adolescents with psychiatric disorders remain diagnostic and therapeutic orphans and far too many receive limited or even inadequate care. Let’s see what we can do to change that. I hope you enjoy these CAP Smart Takes. And please pass on suggestions for topics you would like us to cover and discuss. All the best, and let’s get to it!
In this Child and Adolescent Psychiatry Smart Take, we will look at a concise and elegant review of adolescent depression by Dr. Miller and Dr. Campo, recently published in The New England Journal of Medicine. Now, do we even need another review of adolescent depression? Well, if Dr. Miller and Dr. Campo wrote it, the answer is a resounding yes. It is no wonder that The New England Journal of Medicine decided to devote a special focus to depression in adolescents. We know that rates of depression have increased significantly across the lifespan, but they are skyrocketing in adolescents. We also know that the increased rate of depression in adolescents is significantly greater than in any age group. Suicide is now the second leading cause of death among teenagers and the most common underlying cause of suicide is depression. We also know that since the FDA issued a black box warning for antidepressants in youth in 2004, concerns about potential suicidality associated with using antidepressants have been raised.
So, it is very timely now to examine where we were, where we are now, and where we need to go. We also know that most adults with depression experience their first depressive episode in adolescence. Moreover, depression in adulthood is often predicted by early depression or anxiety. One key question is whether the use of antidepressants in adolescent depression is associated with an increased risk for suicidality. This is something I keenly remember because when this was getting national attention around the world, there was this concern that SSRIs, like paroxetine and others, were no better than placebo, and that was a big question: What is the placebo response? It seemed high, and there were not always delineations or discriminations between medication and placebo.
And there started to be a concern in some studies—was there an increased risk of suicidality, suicidal ideation, and suicide attempts in adolescents treated with SSRIs? I was doing a study funded by the National Institute of Mental Health (NIMH) where we were using paroxetine in children and adolescents. And at that time, the NIMH insisted that we stop using paroxetine in our studies and instead use a different SSRI. Some of you may remember that in the U.K., they stopped using all SSRIs except for fluoxetine. So, many questions remained unanswered, and of course, suicide concern is very concerning in the pediatric setting. We know now that some meta-analyses of several treatment trials analyzed by the FDA found a small but statistically significant difference in suicidal ideation and attempted suicide in adolescents treated with antidepressant medication vs placebo. However, I want you to remember that none of these studies included suicide-specific measures. They all relied on reported adverse events, and all were post-hoc analyses, which means the study of suicidality was done after the fact, not longitudinally or in real-time.
Interestingly, a more recent investigation using suicide-specific measures found no difference in suicide risk between adolescents receiving antidepressant medication or placebo. Finally, it is essential to examine the different populations treated with antidepressants. In adolescents, where this first link was possibly found, this was not seen when SSRIs were used in placebo-controlled treatment trials of adolescents with social anxiety disorder, obsessive-compulsive disorder, or any disorder other than major depressive disorder. Another thing to remember is that the placebo rate, which is often exceptionally high in adolescent depression, appears much lower in federally funded studies than in industry-funded studies. The NIMH Treatment for Adolescents Depression Study—the TAD Study—found a much lower placebo rate than in industry-funded studies. All of the sites on the TAD Study were academic university sites. So, that is one thing to look for in studies comparing placebo and medication.
In the TAD Study, consistent with other studies, we also found that the most effective treatment was fluoxetine plus cognitive–behavioral therapy (CBT), which beat placebo, CBT, and medication alone. Another exciting thing is that there may be a protective effect against suicidality when you combine CBT with medication, and it might help to use lower doses of SSRIs. So, many advantages. Like in diabetes, where we often would use a biological treatment, such as insulin, and psychosocial treatment, such as diet or exercise, here in depression, the biological treatment would be the SSRI and the psychosocial treatment CBT or other psychotherapies. We still do not know why this difference exists with other antidepressants, such as TCAs. These are FDA approved in adults with depression, but they have been found consistently not superior to placebo in child and adolescent depression. Currently, only 2 antidepressants are FDA approved for youth with depression—fluoxetine and escitalopram. Moreover, fluoxetine is the only FDA-approved medication in youth—for both children and adolescents. So, there is much work that still needs to be done.
This article gives a beautiful overview of where we are, what needs to happen going forward, and how we get there. I would have liked for it to discuss alternative treatments in terms of pharmacogenetics, diet, nutrition, and novel agents, such as ketamine, transcranial magnetic stimulations, and electroconvulsive therapy, which have been used at some centers for treatment-resistant depression. However, that does not detract from an excellent and worthwhile read for all those interested in adolescent depression.
Abstract
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Reference
Miller, L., & Campo, J. V. (2021). Depression in adolescents. New England Journal of Medicine, 385(5), 445-449.
