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CBT + Zoloft = Best Treatment for Childhood Anxiety

I hadn’t yet written about the New England Journal of Medicine study by Walkup and colleagues (2008) that found that cognitive behavioral therapy (CBT) and Zoloft (sertraline) are an effective combination to help treat childhood anxiety disorders. The results are robust and the study was one of the best designed in recent years.

CL Psych and Furious Seasons were both happy to see an extensive side effects table was included (and CL Psych noted how CBT has some more disturbing side effects than Zoloft). Philip at Furious Seasons commented more from the perspective of amazement that we continue to prescribe such medications to children as young as eight (and psychiatrists will tell you they’ve written scripts for much younger children than that).

But even when studies with sufficient power, a placebo control group, a thorough randomized sample from multiple clinics, and a thoughtful design are published, critics will find flaws in them. And as much as I can find a flaw with virtually any study, I try and focus on obvious, fatal flaws that would negate or at least call into question a study’s results. This study had no such flaws.

Doug Bemner led the blog charge, suggesting that out of the three assessments used to measure change in each of the four treatment groups, one of them showed something that perhaps wasn’t as significant as the researchers claimed (at least for the medication-only group). He also relied on the old “guilt by association” argument, comparing the new study against a poorly designed 7-year old study. As far as I can tell, the two studies share nothing in common except that they both looked at a medication’s effectiveness in teens (different medications, different disorders, and designed and conducted by different researchers).

Bremner’s off-the-cuff analysis wrongly suggests the current researchers had no specific outcome objectives:

In the sertraline/CBT study, the authors (as far as we know) had “improvement” as their primary outcome. However improvement can be misleading.

Yet, the researchers presented a quite clear definition of how they define improvement:

The categorical primary outcome was the treatment response at week 12, which was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impression–Improvement scale, which ranges from 1 to 7, with lower scores indicating more improvement, as compared with baseline. A score of 1 or 2 reflects a substantial, clinically meaningful improvement in anxiety severity and normal functioning.

They also used two additional scales to measure improvement, which they clearly define in their “Outcome Assessments” category.

Now, the data in the study shows that all groups improved. This is typical for a study, because we know that “placebo response” can often approach the response rates for an active medication. So there’s no surprise there.

A careful reading of the data presented in Table 2 shows some important findings. At week 12, 80% of the combined group had a significant response to treatment, compared to about 24% of the placebo group. So while the placebo group showed a significant decline in their anxiety (as defined by the researchers, a score below 13), their global functioning scores demonstrated they had significantly more distress than the treatment groups, just barely grazing over the threshold that suggests a need of treatment.

No one picking apart the study noted that if you provide a child with the combination treatment, 80% of them will have a significant improvement by week 12, compared to simply giving them a sugar pill (24%). That’s a huge and statistically significant difference.

Importantly, the only group to get to a score of 2 (2.4 to be exact) on the Clinical Global Impression-Improvement scale — their main outcome measure — was the combination therapy group (Zoloft + CBT). This is the primary outcome measure defined by the researchers at the onset of the study and the one where none of the other groups achieved. However, the researchers’ statistical analysis concluded that all three active treatments provided significant improvement over the placebo group.

The other significant finding from the study was the rise of cognitive behavioral therapy as an appropriate treatment, even on its own, for children and teens with moderate to severe anxiety:

This evaluation of cognitive behavioral therapy and other recent studies suggests that such therapy for childhood anxiety is a well-established, evidenced-based treatment.

This was a well-designed and robust study that offers additional data suggesting that any of the three treatments — Zoloft, cognitive behavioral therapy or a combination of the two — were effective for reducing anxiety in children and teens. Combination treatment, however, was found to offer the most relief for the most people who tried it. And cognitive behavioral therapy showed that it can hold its own even in the treatment of moderate to severe anxiety in children and teens.

* * *

Read Furious Seasons’ take: Major Study Of Zoloft And CBT For Kids’ Anxiety Has Its Own Issues

Read CL Psych’s take: You Really Can Report Safety Data


Walkup, J.T. et al. (2008). Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety. NEJM (Dec. 25 issue).

CBT + Zoloft = Best Treatment for Childhood Anxiety

John M. Grohol, Psy.D.

Dr. John Grohol is the founder of Psych Central. He is a psychologist, author, researcher, and expert in mental health online, and has been writing about online behavior, mental health and psychology issues since 1995. Dr. Grohol has a Master's degree and doctorate in clinical psychology from Nova Southeastern University. Dr. Grohol sits on the editorial board of the journal Computers in Human Behavior and is a founding board member of the Society for Participatory Medicine. You can learn more about Dr. John Grohol here.

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APA Reference
Grohol, J. (2019). CBT + Zoloft = Best Treatment for Childhood Anxiety. Psych Central. Retrieved on October 28, 2020, from
Scientifically Reviewed
Last updated: 24 May 2019 (Originally: 3 Nov 2008)
Last reviewed: By a member of our scientific advisory board on 24 May 2019
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