Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder

Varigonda, Anjali L.; Jakubovski, Ewgeni; Taylor, Matthew; Freemantle, Nick; Coughlin, Catherine G.; Bloch, Michael H.

doi:10.1016/j.jaac.2015.05.004

Cited by 41 publications

(28 citation statements)

References 57 publications

(39 reference statements)

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“…The risk/benefit profile of SSRIs demonstrated in this meta‐analysis for anxiety disorders is similar to the previous results in meta‐analyses examining SSRIs for MDD (Jakubovski, Varigonda, Freemantle, Taylor, & Bloch, ) and OCD (Issari et al., ). However, in contrast to the findings of these previous meta‐analyses demonstrating a logarithmic response curve of SSRIs in MDD and OCD (Issari et al., ; Jakubovski et al., ; Varigonda et al., ), the response curve for the benefit of SSRIs over placebo in anxiety disorders follows a linear trajectory with equal benefits of medication observed over the first 12 weeks of treatment. The difference in the shape of the response curve in anxiety disorders (with decreased benefits of SSRIs compared to placebo observed early in treatment) may be due to the fact that in most RCTs in anxiety disorders (compared to those in OCD and MDD), slower titration schedules were used due to concerns about triggering panic attacks and other anxiety symptoms early in treatment.…”

Section: Discussioncontrasting

confidence: 90%

“…This meta‐analysis suggests a reduced treatment benefit based on year of publication in RCTs using SSRI/SNRI in adults with anxiety disorders. Similar phenomena have been observed in MDD and OCD (Issari et al., ; Jakubovski et al., ; Varigonda et al., ) and are likely related to changing subject populations in later trials. Specifically, as SSRIs/SNRIs became more and more available to patients in usual care in recent years, many subjects were only willing to enroll in a placebo‐controlled trial if they experienced failed trials of other medications (with the same mechanism of action).…”

Section: Discussionsupporting

confidence: 72%

“…The statistical analysis for this trial was adapted from a previously published meta-analysis examining the response curve of SSRIs for the treatment of MDD and OCD (Issari, Jakubovski, Bartley, Pittenger, & Bloch, 2016;Taylor, Freemantle, Geddes, & Bhagwagar, 2006;Varigonda et al, 2015). Data collection and preparation were conducted in Microsoft Excel 2007.…”

Section: Meta-analysis Methodsmentioning

confidence: 99%

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Systematic review and meta-analysis: Dose-response curve of SSRIs and SNRIs in anxiety disorders

et al. 2018

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Background We aimed to examine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for anxiety disorders examining overall symptom improvement, likelihood of treatment response, time course of treatment response, individual pharmacological agent, diagnostic indication dose, and tolerability. Methods We searched PubMed and Cochrane Central Register of Controlled Trials. We included randomized placebo‐controlled clinical trials of SSRIs/SNRIs in adult patients with anxiety disorders that provided data at three or more time points. Extracted data included trial duration, weekly/biweekly anxiety scores for 12 weeks. Results Meta‐analysis included 57 trials (N = 16,056). A linear mixed model analysis based on weekly outcome data suggested that for SNRI a logarithmic model offered the best fit compared to placebo (indicating the greatest incremental improvement from baseline occurred early in treatment); whereas for SSRI a linear model provided the best fit (indicating a similar improvement over the duration of the acute treatment phase). There were no significant differences in efficacy between pharmacological agents within each class or when comparing SSRIs to SNRIs. The greatest treatment benefits were observed for social anxiety disorder for both medication classes. Higher doses of SSRIs, but not SNRIs, were associated with significantly greater symptom improvement and likelihood of treatment response. For both medical classes, higher doses were associated with an increased likelihood of dropout due to side effects. Conclusions SSRIs and SNRIs are effective in treating anxiety disorders. Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.

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Section: Discussioncontrasting

confidence: 90%

Section: Discussionsupporting

confidence: 72%

Section: Meta-analysis Methodsmentioning

confidence: 99%

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Systematic review and meta-analysis: Dose-response curve of SSRIs and SNRIs in anxiety disorders

et al. 2018

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“…In this study, there was no relationship between the dose of the medication and response. 31 This finding should be interpreted with caution, given a number of causal inferences. Specifically, it is likely that patients who had exhibited response to an antidepressant would be unlikely to have their antidepressant dose titrated by the treating clinician.…”

Section: Introductionmentioning

confidence: 92%

Primary Pediatric Care Psychopharmacology: Focus on Medications for ADHD, Depression, and Anxiety

Dobson

Giles

2017

Current Problems in Pediatric and Adolescent Health Care

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The evidence base for psychopharmacologic interventions in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) has dramatically increased over the past two decades. Psychopharmacologic interventions commonly utilized in the pediatric primary care setting—selective serotonin (norepinephrine) reuptake inhibitors (SSRIs/SSNRIs), stimulants and α2 agonists—are reviewed. General pharmacologic principles are summarized along with class-related side effects and tolerability concerns (e.g., suicidality and activation in antidepressant-treated youth as well as insomnia, irritability, anorexia in stimulant-treated pediatric patients). Selected landmark trials of antidepressant medications in youth with depressive disorders (Treatment of Adolescent Depression Study [TADS] and the Treatment of SSRI-Resistant Depression Study [TADS]) and anxiety disorders (Child/Adolescent Anxiety Multimodal Study [CAMS] and Child/Adolescent Anxiety Multimodal Extended Long-term Study [CAMELS]) are described in addition to the Multimodal Treatment of ADHD Study. Finally, available data are presented that are related to prediction of treatment outcomes in youth with depressive disorders, anxiety disorders and ADHD.

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“…In contrast, a meta‐analysis of randomized, placebo‐controlled trials in pediatric depression suggests that the greatest incremental treatment gains of SSRIs compared to placebo are seen earlier in treatment and are statistically significant by 2 weeks into treatment (Varigonda et al, ). On average, nearly half of the treatment benefits of SSRIs over placebo are observed at 2 weeks and more than two thirds of the gains are apparent at 4 weeks of treatment (Varigonda et al, ). These data suggest that early treatment gains to antidepressant treatment in pediatric MDD may be strongly predictive of overall response.…”

Section: Evaluating Treatmentmentioning

confidence: 99%

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Dwyer

Stringaris

Brent

et al. 2020

Child Psychology Psychiatry

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Background Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard‐of‐care treatments (psychotherapy and medication), roughly one third will not. Methods Here, we have reviewed the literature in order to discuss the concept of treatment‐resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. Results We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first‐ and second‐line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence‐based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. Conclusions As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.

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Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder

Cited by 41 publications

References 57 publications

Systematic review and meta-analysis: Dose-response curve of SSRIs and SNRIs in anxiety disorders

Systematic review and meta-analysis: Dose-response curve of SSRIs and SNRIs in anxiety disorders

Primary Pediatric Care Psychopharmacology: Focus on Medications for ADHD, Depression, and Anxiety

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

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