Monotherapy Insufficient in Severe Anxiety? Predictors and Moderators in the Child/Adolescent Anxiety Multimodal Study

Abstract

This secondary analysis of the Child/Adolescent Anxiety Multimodal Study (CAMS) used baseline patient characteristics to identify prognostic subgroups of children based on likelihood of remission. We also investigated predictors and moderators of outcome. CAMS randomized 488 youths with generalized, social, and separation anxiety disorders to cognitive behavioral therapy (CBT), sertraline, both, or pill placebo. Outcomes were Week 12 child, parent, and independent evaluator (IE) ratings of child anxiety. We used receiver operating characteristics analysis and stepwise regression to identify predictors and moderators of outcome. Severe anxiety, lower socioeconomic status, and comorbid obsessive-compulsive disorder predicted higher IE-rated anxiety posttreatment; child-rated social anxiety predicted poorer outcomes reported by all informants. Regarding moderators, Hispanic ethnicity predicted higher IE-rated anxiety after CBT and higher parent-rated anxiety after sertraline. In youths with severe anxiety (Pediatric Anxiety Rating Scale ≥ 20, <italic>n</italic> = 220), combination treatment increased remission (relative risk [RR] = 2.85, <italic>p</italic> < .001), 95% confidence interval (CI) [1.51, 5.39], whereas CBT (RR = 1.55, <italic>p</italic> = .20), 95% CI [0.77, 3.10], and sertraline (RR = 1.27, <italic>p</italic> = .53), 95% CI [0.59, 2.73], did not significantly increase remission relative to placebo. These are the first findings demonstrating that a combination of CBT and a selective serotonin reuptake inhibitor, not monotherapy, is likely key for achieving remission in severe anxiety. CAMS was not powered to detect treatment efficacy after stratification by anxiety severity, so further research is needed regarding effective treatments in severe anxiety. Our main effect findings suggest youth with severe anxiety (especially social phobia), low socioeconomic status and obsessive-compulsive disorder benefit less from current first-line treatments relative to other anxious youth. ClinicalTrials.gov: NCT00052078.

Association of anxiety phenotypes with risk of depression and suicidal ideation in community youth

“…This pattern might implicate midadolescence as the first developmental window during which specific brain circuitries can be linked to anxiety subtypes. The finding has implications for anxiety clinical trials, as pediatric anxiety trials often combine anxiety disorders (Compton et al, 2010;Taylor et al, 2018), and our findings suggest that though such an approach may be appropriate in children, it may require revisiting in adolescent populations.…”

“…Despite the significant heterogeneity of anxiety disorders (Williams et al, 2016), there is substantial overlap in the manifestation and treatment of anxiety across anxiety disorders in youths (Rey & Martin, 2019;Taylor et al, 2018). Indeed, past work suggests that for preadolescents the strong overlap among anxiety symptoms may obscure the presence of specific types of anxieties (Ferdinand, Lang, Ormel, & Verhulst, 2006).…”

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial

“…A possible explanation for the carryover effects of ketamine is that when a subject's social anxiety was reduced, the subject participated in more social activities. Increased exposure to social activities is a treatment for SAD (eg CBT) (Peris et al, 2015;Roy-Byrne et al, 2010;Taylor et al, 2015;Taylor et al, 2017b) and may have maintained ketamine's anxiolytic effects. Several participants reported increased social engagement in the days following ketamine infusion; however, we did not systematically track social exposure, and further research is needed to substantiate this hypothesis.…”

“…SAD (also known as social phobia) typically negatively impacts academic achievement, work productivity, social relationships, and quality of life (Lipsitz and Schneier, 2000;Taylor et al, 2015;Taylor et al, 2016;Taylor et al, 2017a) and is associated with subsequent development of depression, alcoholism, and cardiovascular disease (Kessler, 2003;Kessler et al, 2005). Roughly one-third to one-half of patients with SAD do not experience significant clinical benefit from current evidence-based treatment for SAD such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or venlafaxine and cognitive behavioral therapy (CBT) (Kelly et al, 2014;Roy-Byrne et al, 2010;Taylor et al, 2015;Taylor et al, 2017b). Inadequate anxiety relief in patients with SAD is a source of substantial morbidity, distress, and decreases in quality of life.…”

“…Inadequate anxiety relief in patients with SAD is a source of substantial morbidity, distress, and decreases in quality of life. Novel pharmacological treatments are needed to improve outcomes in patients with SAD (Liebowitz et al, 2016;Taylor et al, 2015;Taylor et al, 2017b).…”