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Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder - 16/06/15

Doi : 10.1016/j.jaac.2015.05.004 
Anjali L. Varigonda, MD a, Ewgeni Jakubovski, MA b, Matthew J. Taylor, MRCPsych d, Nick Freemantle, PhD e, Catherine Coughlin, BS b, Michael H. Bloch, MD, MS b, c,
a University of Vermont Medical Center, Burlington 
b Yale Child Study Center, New Haven, CT 
c Yale University 
d University of Oxford, UK 
e University of Birmingham, Edgbaston, Birmingham, UK 

Correspondence to Michael H. Bloch, MD, MS, Child Study Center, Yale University School of Medicine, PO Box 2070900, New Haven, CT 06520

Abstract

Objective

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for pediatric major depressive disorder (MDD). We conducted a meta-analysis to examine the following: the time-course of response to SSRIs in pediatric depression; whether higher doses of SSRIs are associated with an improved response in pediatric depression; differences in efficacy between SSRI agents; and whether the time-course and magnitude of response to SSRIs is different in pediatric and adult patients with MDD.

Method

We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs to placebo for the treatment of pediatric MDD. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on standardized mean differences between treatment and placebo groups.

Results

The meta-analysis included 13 pediatric MDD trials with a total of 3,004 patients. A logarithmic model indicating that the greatest benefits of SSRIs occurred early in treatment best fit the longitudinal data (log[week] = 0.10, 95% CI = 0.06–0.15, p < .0001). There were no significant differences based on maximum SSRI dose or between particular SSRI agents. SSRIs were demonstrated to have a smaller benefit in pediatric compared to adult MDD.

Conclusion

Treatment gains in pediatric MDD are greatest early in treatment and are, on average, minimal after 4 weeks of SSRI pharmacotherapy in pediatric MDD. Further research is needed using individual patient data to examine the power of early SSRI response (e.g., 2–4 weeks) to predict outcomes in short-term pharmacological trials.

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Key Words : MDD, meta-analysis, serotonin reuptake inhibitors


Plan


 Clinical guidance is available at the end of this article.
 This article was reviewed under and accepted by deputy editor John T. Walkup, MD.
 The authors gratefully acknowledge support from the National Institutes of Health/National Institute of Mental Health (1K23MH091240), the Trichotillomania Learning Center, the Yale Child Study Center Research Training Program, the APIRE/Eli Lilly and Co. Psychiatric Research Fellowship, the AACAP/Eli Lilly and Co. Junior Investigator Award, NARSAD, and UL1 RR024139 from the National Center for Research Resources, a component of the National Institutes of Health, and NIH roadmap for Medical Research.
 Disclosure: Dr. Bloch has received grant or research support from the NIH K23 Award, the Trichotillomania Learning Center, the Tourette Syndrome Association, the Patterson Foundation, NARSAD, the Rembrandt Foundation, and the American Academy of Child and Adolescent Psychiatry Research Initiative Junior Investigator Award. Drs. Varigonda, Taylor, Freemantle, Mr. Jakubovski, and Ms. Coughlin report no biomedical financial interests or potential conflicts of interest.


© 2015  Publié par Elsevier Masson SAS.
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Vol 54 - N° 7

P. 557-564 - juillet 2015 Retour au numéro
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