01. The Role of Escitalopram in Treating Generalized Anxiety Disorder in Youth

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Greetings; this is David Rosenberg from the Psychopharmacology Institute. In this Child and Adolescent Psychiatry (CAP) Smart Take, we shall examine a multicenter, double-blind, placebo-controlled trial of escitalopram in children and adolescents with generalized anxiety disorder (GAD). This is highly significant as currently, there are no FDA-approved medications for youth with anxiety disorders. Previous double-blind, placebo-controlled trials have suggested that selective serotonin reuptake inhibitors (SSRIs), including escitalopram, are effective in adolescents with GAD. However, there is limited information about preadolescent and prepubertal children suffering from GAD. It is also understood that GAD can lead to future depression. At least one-third of GAD patients currently suffer from major depressive disorder (MDD), whereas two-thirds will develop MDD at some point during their illness—making this a critical area of study.

Strawn and colleagues assessed children and adolescents aged 7–17 years diagnosed primarily with GAD treated with flexibly dosed escitalopram 10 mg–20 mg/day. The study involved 138 pediatric patients with GAD treated with medication vs placebo—of which there were 137 patients—a large multicenter study indeed. The patients were treated for 8 weeks.

So, what were the findings? Primarily, escitalopram was significantly superior compared with the placebo in reducing anxiety symptoms in children and adolescents suffering from GAD. Significant changes were observed from baseline to week 8, with significantly more improvement noted in the escitalopram group compared with the placebo group. Another positive aspect of this study was that the medication was well-tolerated; no significant differences concerning discontinuation due to adverse events between the placebo and medication groups were noted.

I believe another noteworthy point is that escitalopram has the fewest drug–drug interactions among all medications—making it safer for patients with comorbid medical or other psychiatric conditions. It may be safer compared with other SSRIs, which have more drug–drug interactions, particularly a medication like fluoxetine.

This study confirms prior studies demonstrating escitalopram’s efficacy in adolescents and extends the safety efficacy and tolerability into children aged 7–11 years—a crucial finding aiding clinicians in practice.

However, the study does have limitations. Firstly, this was an industry-funded study; several investigators received support from the sponsor. Although it is one of the largest prospective trials of an SSRI in pediatric patients with anxiety disorders—a significant advantage—the 8-week time frame is relatively short. There were only 2 postbaseline efficacy measures, limiting the ability to examine specific domains of response and functional forms of response fully. More information regarding comorbidity would be beneficial given that GAD in youth is a highly comorbid illness—it would be important to know how comorbidity impacts response or lack thereof. Similarly, more information about the supportive therapy used during treatment and its potential impact on response is needed given prior studies—including the Treatment of Adolescent Depression Study I participated in, where we found combination therapy of cognitive–behavioral therapy (CBT) and antidepressant treatment to be most effective for adolescents with MDD.

There exists a National Institute of Mental Health–funded study in youth suffering from various anxiety disorders—including but not limited to GAD—which found that the SSRI sertraline plus CBT was more effective than not only placebo but also CBT alone or SSRI alone. Therefore, this current study suggests that escitalopram plays a role in pediatric GAD, demonstrating superior efficacy compared with placebo. Nonetheless, it must be incorporated into our armamentarium judiciously—considering its usage alongside CBT, its role in various comorbid conditions, and its attractiveness to patients on other medications due to fewer drug–drug interactions.

As a side note, SSRIs like escitalopram are more likely to have what I would refer to as an “oh wow effect” in anxiety disorders such as GAD compared with depression, where the response can often be more subtle.

Abstract

A Multicenter Double-Blind, Placebo-Controlled Trial of Escitalopram in Children and Adolescents with Generalized Anxiety Disorder

Jeffrey R Strawn, Leslie Moldauer, Rebekah D Hahn, Alexandria Wise, Kristina Bertzos, Beth Eisenberg, Edward Greenberg, Chengcheng Liu, Mallika Gopalkrishnan, Molly McVoy, James A Knutson

Objective: Generalized anxiety disorder (GAD) in children and adolescents is associated with substantial morbidity and increases the risk of future psychopathology. However, relatively few psychopharmacologic studies have examined treatments for GAD in pediatric populations, especially in prepubertal youth. Methods: Children and adolescents aged 7-17 years of age with a primary diagnosis of GAD were treated with flexibly dosed escitalopram (10-20 mg daily, n = 138) or placebo (n = 137) for 8 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS) for GAD, Clinical Global Impression of Severity (CGI-S) scale, Children’s Global Assessment Scale (CGAS); safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as adverse events (AEs), vital signs, and electrocardiographic and laboratory monitoring. Results: Escitalopram was superior to placebo in reducing anxiety symptoms of GAD, as seen in the difference in mean change from baseline to week 8 on the PARS severity for GAD score (least squares mean difference = -1.42; p = 0.028). Functional improvement, as reflected by CGAS score, was numerically greater in escitalopram-treated patients compared with those receiving placebo (p = 0.286), and discontinuation owing to AEs did not differ between the two groups. Vital signs, weight, laboratory, and electrocardiographic results were consistent with previous pediatric studies of escitalopram. Conclusions: Escitalopram reduced anxiety symptoms and was well tolerated in pediatric patients with GAD. These findings confirm earlier reports of escitalopram efficacy in adolescents aged 12-17 years and extend the safety and tolerability data to children with GAD aged 7-11 years.

Reference

Strawn, J. R., Moldauer, L., Hahn, R. D., Wise, A., Bertzos, K., Eisenberg, B., Greenberg, E., Liu, C., Gopalkrishnan, M., McVoy, M., & Knutson, J. A. (2023).

A multicenter double-blind, placebo-controlled trial of escitalopram in children and adolescents with generalized anxiety disorder

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Journal of Child and Adolescent Psychopharmacology, 33

(3), 91-100.