The use of the selective serotonin reuptake inhibitor (SSRI) sertraline (Zoloft, Pfizer Inc) to treat anxiety disorders in children and adolescents is safe and is associated with a tolerable adverse event (AE) profile, according to the results of an in-depth analysis of four treatment conditions in the Child/Adolescent Anxiety Multimodal Study (CAMS).
After carefully probing the AEs occurring within each of the four treatment arms ― cognitive-behavioral therapy (CBT), sertraline (SRT), a combination of both (COMB), or pill placebo (PBO) ― the researchers could find no differences in overall rates of AEs.
However, they did find a higher rate of psychiatric AEs in children aged 12 years and younger, leading them to advise additional, more vigilant monitoring in this younger age group.
The study, led by Moira A. Rynn, MD, from Columbia University Medical Center/New York State Psychiatric Institute, New York City, was published in the March issue of the Journal of the American Academy of Child and Adolescent Psychiatry.
In-depth Analysis
A multicenter, randomized, placebo-controlled CAMS compared the use of SRT, CBT, COMB, and PBO during a 12-week period in 488 children and adolescents diagnosed with separation anxiety disorder, generalized anxiety disorder, or social phobia.
At the end of 12 weeks, the response with COMB treatment was superior to that with both CBT and SRT. The response rate for COMB was 80.7%; for CBT, 59.7%; and, for SRT 54.9%. All active treatments were more effective than PBO, which was associated with a response rate of 23.7%.
An analysis of the AEs in CAMS focused on comparisons between SRT vs PBO and SRT vs CBT; there were no differences in the frequency of moderate to severe AEs, including suicidal and homicidal ideation, with SRT vs PBO.
However, for CBT, insomnia, fatigue, and restlessness occurred less frequently in comparison with SRT. The analysis did not include comparisons between SRT and COMB, because COMB was an open treatment condition, and participants knew they were taking medication.
In the current article, the authors extended results of a previous analysis of AEs by comparing the frequency of AEs across all four treatment conditions, including COMB. They also compared AEs in children and adolescents.
Of the 488 participants, 74% were aged 12 years or younger.
This more in-depth analysis showed no differences between SRT and PBO for physical or psychiatric AEs. However, SRT was associated with higher rates of physical AEs compared with CBT or COMB, but not compared with PBO.
Participants in the SRT group reported higher rates of insomnia (P < .01), fatigue (P < .01), and sedation (P < .05) than participants in the CBT or COMB treatment groups.
Worsening and emergence of new self-reported physical symptoms during acute treatment, which were evaluated with the use of a Physical Symptom Checklist, occurred more often in the PBO treatment group than in the SRT treatment group.
These included increased symptoms of stomach pain (21.4% vs 9.6%, P < .05), difficulty breathing (9.1% vs 1.1%, P < .05), and numbness or tingling in the arms or legs (9.1% vs 0%, P < .01).
However, a greater percentage of participants receiving SRT reported worsening or new onset of sleep difficulty compared with PBO participants (27.7% vs 13.0%, P < .05).
Higher AE Rate in Younger Children
The rate of total psychiatric AEs was higher in children aged 12 years or younger than in adolescents in all of the treatment conditions (31.7% vs 23.1%, P < .05).
When individual treatments were compared, SRT showed significantly higher rates of psychiatric AEs compared with CBT (P < .05).
COMB participants had more psychiatric AEs than did CBT participants. These included more disinhibition (P < .05) and increased motor activity (P < .05).
COMB participants also had more suicidal/homicidal ideation and behaviors compared with SRT or PBO participants (P < .05 for both treatments).
There were no suicide attempts in any treatment condition.
"The findings reported in this article support the mounting data suggesting the tolerability and safety of acute SSRI treatment for pediatric anxiety disorders. More specifically, no significant differences in the overall rate of physical or psychiatric AEs were found when comparing the 2 blinded treatments arms, SRT and PBO, using the systematic inquiry method," the authors write.
The investigators note that the study has several limitations, including use of post hoc analyses, which "may result in spurious association between treatment and AEs."
They also caution that although their study adds information about AEs with SSRIs in youth treated for anxiety disorders, the results may not be generalizable to youth receiving SSRIs for the treatment of other psychiatric disorders.
"Sertraline was well tolerated, and the benefits outweigh the adverse effects associated with the use of SSRIs in youth with anxiety. The results from this secondary analysis highlight the need for careful assessment and monitoring of AEs with SSRI treatment for children and adolescents diagnosed with anxiety disorders," the authors continue.
"It is the responsibility of the treatment provider to inform, educate, and help the child or adolescent and his or her family to assess the benefits versus the risk of all the treatment options and to understand which modality is the best initial choice for his or her particular need," they conclude.
Risks Still an Issue
In an accompanying editorial, Floyd R. Sallee, MD, PhD, from the College of Medicine, University of Cincinnati, in Ohio, notes that the findings provide "additional reassurance" of short-term tolerability and safety of SSRIs and "coincides with ever-increasing prescribing rates" for these medications "for children and adolescents with anxiety disorders among generalists and specialists treating these conditions."
The benefit side of the risk-to-benefit ratio is becoming clearer with SSRIs in the treatment of anxiety in children and adolescents. However, the risks remain at issue, Dr Sallee notes.
He points out that CAMS exposure to SSRI was limited to 12 weeks, but SSRI treatments for anxiety disorder in youth typically continue for at least 1 year.
"In this regard, we have no answers to the long-term risk of SSRI exposure by age or stage of brain development... It is important that we have long-term longitudinal studies that follow therapeutic outcomes and AEs over time," Dr Sallee concludes.
The research was supported by grants from the National Institute of Mental Health (NIMH). Sertraline and matching placebo were provided by Pfizer. Dr Rynn reports financial relationships with the National Institutes of Health, the NIMH, the National Institute of Child Health and Human Development, Eli Lilly and Co, Pfizer, Merck, Shire, American Psychiatric Publishing, Oxford University Press, the American Academy of Child and Adolescent Psychiatry, and the American Society of Clinical Psychopharmacology. Dr Sallee reports financial relationships with the NIMH, Ironshore Pharmaceuticals, AstraZeneca, Impax Laboratories, Purdue Pharma, Otsuka Research and Development, and Reckitt Benckiser and that he is a member of the board of directors and a stockholder of P2D Bioscience.
J Am Acad Child Adolesc Psychiatry. 2015;54:180-190. Abstract, Editorial
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Cite this: SSRIs Safe, Tolerable for Pediatric Anxiety - Medscape - Mar 11, 2015.
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