A Randomized, Placebo-Controlled Study of Duloxetine for the Treatment of Children and Adolescents With Generalized Anxiety Disorder

Strawn, Jeffrey R.; Prakash, Apurva; Zhang, Qi; Pangallo, Beth A.; Stroud, Chad; Cai, Na; Findling, Robert L.

doi:10.1016/j.jaac.2015.01.008

Cited by 83 publications

(80 citation statements)

References 36 publications

(49 reference statements)

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“…However, these disorders are also amenable to both psychotherapeutic and psychopharmacologic interventions (Connolly and Bernstein 2007;Walkup et al 2008;Strawn et al 2015a;Strawn et al 2015b), and long-term data suggest that successful treatment may result in sustained reductions in anxiety .…”

Section: Introductionmentioning

confidence: 99%

Placebo Response in Pediatric Anxiety Disorders: Implications for Clinical Trial Design and Interpretation

Dobson

2016

Journal of Child and Adolescent Psychopharmacology

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Objectives: The characterization and prediction of placebo response in clinical trials of youth with anxiety disorders have received little attention, despite the critical effects of placebo response rate on the success or failure of clinical trials. With this in mind, we sought to examine the factors that predict or influence placebo response in randomized controlled trials of youth with anxiety disorders. Methods: Prospective, randomized, parallel-group controlled trials of psychopharmacologic interventions in pediatric patients with anxiety disorders were identified using a search of PubMed/Medline (1966. Weighted least squares regression models and z-tests were utilized to examine the impact of continuous and categorical variables, respectively, on placebo response. These variables included demographic (e.g., age, percent white, percent female), clinical (e.g., baseline symptom severity), and trial characteristics (sample size, duration, funding). Finally, the relationship between the class of comparator medication and placebo response rate was examined using a multiple comparison for proportions test.Results: The analyses of data from 14 trials involving 2230 patients and 9 medications reveal that higher placebo response rates were associated with a greater number of study sites ( p = 0.013) and fewer patients per site ( p < 0.008), while placebo dropout rates increased with more recent publication ( p = 0.01) and were positively associated with the number of study visits ( p < 0.02). Lower placebo response rates were associated with federally funded studies (z = -4.61, p < 0.001), studies conducted in the United States (z = 1.81, p < 0.035), and with an increased likelihood of detecting a significant effect on the primary outcome (z = 4.58, p < 0.0001). Additionally, studies, in which the majority of patients (>60%) had a diagnosis of social anxiety disorder, exhibited lower placebo response rates ( p < 0.001). Finally, for trials, effect size has decreased over time ( p = 0.004). Conclusions: Important trial-specific factors affect placebo response and placebo dropout in youth with anxiety disorders and have pragmatic implications for the conduct and design of clinical trials and raise the possibility that limiting the number of sites while maximizing the number of patients per site could enhance the ability to detect medication-placebo differences.

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Section: Introductionmentioning

confidence: 99%

Placebo Response in Pediatric Anxiety Disorders: Implications for Clinical Trial Design and Interpretation

Dobson

2016

Journal of Child and Adolescent Psychopharmacology

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“…Unfortunately, duloxetine was not compared with CBT in this trial nor was it explored as an augmentation agent to boost the effects of CBT, potentially resulting in even greater outcomes than when used alone. While considerable evidence supports the use of SSRIs over placebos for paediatric anxiety disorders, at least this one study by Strawn and colleagues32 demonstrates the efficacy of a SNRI, providing an additional avenue to explore if the SSRIs are not shown to be effective augmentation strategies. We exercise additional caution here however as a variety of symptoms including dizziness, lightheadedness, excessive sweating, irritability, dysphoria and insomnia have been reported when these medications are both administered and discontinued.…”

Section: Discussionmentioning

confidence: 94%

“…However, this difference was no longer present at 6 months or 6-year follow-up, as all treatments were equally effective. More recently, the serotonin norepinephrine reuptake inhibitor (SNRI) duloxetine was shown to be more effective than a pill placebo in children and adolescents with generalised anxiety in a randomised control trial 32. Unfortunately, duloxetine was not compared with CBT in this trial nor was it explored as an augmentation agent to boost the effects of CBT, potentially resulting in even greater outcomes than when used alone.…”

Section: Discussionmentioning

confidence: 99%

Innovations in the psychosocial treatment of youth with anxiety disorders: implications for a stepped care approach

Ollendick

Öst

Farrell

2018

Evid Based Mental Health

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Anxiety disorders are highly prevalent among children and adolescents and frequently result in impairments across multiple domains of life. While psychosocial interventions, namely cognitive-behavioural therapy (CBT), have been found to be highly effective in treating these conditions, significant numbers of youth simply do not have access to these evidence-based interventions, and of those who do, a substantial proportion (up to 40%) fail to achieve remission. Thus, there is a pressing need for innovation in both the delivery of evidence-based treatments and efforts to enhance treatment outcomes for those who do not respond to standard care. This paper reviews current innovations attempting to address these issues, including evidence for brief, low-intensity approaches to treatment; internet delivered CBT and brief, high-intensity CBT. Moreover, we propose a model of stepped care delivery of evidence-based mental health interventions for children and youth with anxiety. In general, a stepped care approach begins with a lower intensity, evidence-based treatment that entails minimal therapist involvement (ie, brief, low-intensity self-help or internet delivered CBT) and then proceeds to more intensive treatments with greater therapist involvement (ie, brief high-intensity CBT), but only for those individuals who show a poor response at each step along the way. Future research is needed in order to evaluate such a model, and importantly, to identify predictors and moderators of response at each step, in order to inform an evidence-based, fully-integrated stepped care approach to service delivery.

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“…However, these studies are summarized in Appendix Table E. [8][9][10][11][12][13][14][15][16][17][18][19]. 52 studies (47 RCTs and 5 non-randomized comparative studies) compared different CBTs in terms of components (exposure session, cognitive strategy, and/or relaxation strategy), treatment intensity, parent involvement, and delivery mode (individual-based versus groupbased).…”

Section: Literature Searches and Evidence Basementioning

confidence: 99%

“…The potential disadvantages of pharmacotherapy are that it has unknown effect on brain chemistry, has the potential for adverse events (AEs), 15,16 and that its benefits may not persist after treatment has been discontinued. 17,18 Currently, existing treatment guidelines provide inconsistent and at times conflicting advice. 10,11,19 Regarding SSRIs, one guideline specifically recommends that SSRIs should not be used in children, 11 while another recommends they be used if CBT is not sufficient, 10 and the third recommends their use for more severe presentations or if CBT is not available.…”

Section: Introduction Backgroundmentioning

confidence: 99%

Anxiety in Children

Wang¹,

Whiteside²,

Sim³

et al. 2017

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A Randomized, Placebo-Controlled Study of Duloxetine for the Treatment of Children and Adolescents With Generalized Anxiety Disorder

Cited by 83 publications

References 36 publications

Placebo Response in Pediatric Anxiety Disorders: Implications for Clinical Trial Design and Interpretation

Placebo Response in Pediatric Anxiety Disorders: Implications for Clinical Trial Design and Interpretation

Innovations in the psychosocial treatment of youth with anxiety disorders: implications for a stepped care approach

Anxiety in Children

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