02. Impact of ADHD Medications on Anxiety and Depression in Youth

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This is Dr. David Rosenberg here for the Psychopharmacology Institute. In this CAP—or Child and Adolescent Psychiatry—Smart Take, we will examine the impact of medicines commonly used to treat ADHD on anxiety and depressive symptoms. This is important because anxiety and depression are listed as common side effects of medicines that are FDA approved for treating ADHD in children and adolescents. So, the authors did a comprehensive meta-analysis looking at randomized controlled trials in patients with ADHD to look at the effect that medications have on the signs and symptoms of anxiety and depression. Interestingly, compared with placebo control, there was no significant effect of the medication on symptoms of anxiety or depression. However, there were some problems with the study, not by the way it was designed but by the lack of information; there was a lack of mental health outcomes in these drug trials.

So, all too often, anxiety or depression as a side effect—an objective measure in these clinical drug trials—was not analyzed. We also know that, independent of medicine, many children and adolescents with ADHD who are not on medication suffer from comorbid depression and/or anxiety. That is to say that depression and anxiety commonly occur in patients with ADHD; also, having a diagnosis of ADHD increases the risk of subsequently developing depression and anxiety. We know, for example, that ADHD is associated very strongly with poor self-esteem. Moreover, if poor self-esteem is not improved, if ADHD is not treated adequately, it can, independent of any medication, increase the risk for associated depression and anxiety and create a vicious circle and spiral. So, the worse the ADHD gets, the worse it can make depression and anxiety. And the worse the depression and anxiety are, the worse they can make ADHD.

There is also a fair amount of overlap. Anxious patients may fidget much, similar to what you see in ADHD. Patients with depression and anxiety can have significant problems with attention and concentration, similar to what is experienced in ADHD. This is all to say that it is just not a simple equation. This meta-analysis did not yield evidence that ADHD medicines significantly affected anxiety or depression in children and adolescents. However, we need to do a deeper dive because, after licensing so many of these ADHD medicines, reporting suggests that anxiety and depression are common side effects of ADHD medicines when taken by children and adolescents.

Nevertheless, again, a systematic study is necessary because, all too often, anxiety and depression are not measured at baseline before the patient is treated with ADHD medications. The comorbidity of depression and anxiety in ADHD, as we have discussed, is very high. Unfortunately, the prior clinical trials that have led to various ADHD medications being FDA approved for ADHD have not always examined or measured anxiety and depression.

So, like with sleep, which we know is independent of ADHD medication, patients with ADHD have notoriously poor sleep; the same can be said for anxiety and depression. Moreover, given this dichotomy and discrepancy in what is and what is not a risk for depression and anxiety, this is something where we need standardized measurements of mental health outcomes in children and adolescents with ADHD. That is recommended by these authors, as well as many others. So, the bottom line: This is an important lead; it suggests that anxiety and depression may not be related to medication prescriptions and may be more associated with comorbidity; the risk of depression and anxiety seems independent of medication.

However, this is an important and understudied area, and we do not have enough information from the existing ADHD drug trials to specifically know whether there is or is not an increased risk for depression and anxiety in patients treated with the commonly used medicines to treat ADHD. So, we need standardized measurements before and after medication to enhance our knowledge.

Abstract

A Meta-Analytic Review of the Impact of ADHD Medications on Anxiety and Depression in Children and Adolescents

Annie Bryant, Hope Schlesinger, Athina Sideri, Joni Holmes, Jan Buitelaar, Richard Meiser-Stedman

Anxiety and depression are listed as common side effects for medications licensed for treating ADHD in children and adolescents. This meta-analytic review of randomised controlled trials aimed to explore the effect of medications on symptoms of anxiety and depression in children and adolescents with ADHD. A meta-analytic review of ADHD drug trials in children and adolescents was conducted. Random effects meta-analyses were conducted on anxiety and depression outcomes measured by validated psychological scales or side effect rating scales. Only 11% of eligible trials in this review reported anxiety and/or depression as an outcome or side effect, limiting the conclusions of the meta-analyses. Relative to placebo control, no significant effect of medication was found for symptoms of anxiety or depression in randomised controlled trials of ADHD medication in children and adolescents. This review highlights the systemic lack of mental health outcome reporting in child and adolescent ADHD drug trials. The importance of widespread implementation of standardised measurement of mental health outcomes in future trials is discussed.

Reference

Bryant, A., Schlesinger, H., Sideri, A., Holmes, J., Buitelaar, J., & Meiser-Stedman, R. (2022). A meta-analytic review of the impact of ADHD medications on anxiety and depression in children and adolescents. European Child & Adolescent Psychiatry.