Don't Dally on SSRI Dosing for Anxious Kids



NEW YORK – "Start low, go slow" is the typical mantra of child psychopharmacology, but it might do an enormous disservice to children with anxiety disorders.

While antidepressants can really help these children, most physicians use far too low a dose to effectively control symptoms, Dr. John T. Walkup said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

"If you use too low a dose, you won’t get the quality of effect that you could," said Dr. Walkup, vice chair of child and adolescent psychiatry at the New York–Presbyterian Hospital/Weill Cornell Medical Center. "This leaves kids with the stigma of being on medicine and the stigma of having residual treatment. I can’t think of anything meaner to do to a kid. Please, please, think about pushing the doses of these medicines so that you give kids a chance to respond the best that they can."

Selective serotonin reuptake inhibitors (SSRIs) have proven benefits for anxious children, but almost no one doses young patients in the studied amounts, he said. The Child/Adolescent Anxiety Multimodal Study is an example of successful higher SSRI doses (N. Engl. J. Med. 2008;359:2753-66).

"Please, please think about pushing the doses of these medicines so that you give kids a chance to respond the best that they can."

The 12-week trial randomized 488 children with anxiety disorders to cognitive-behavioral therapy, sertraline, or a combination of both. The dosing design was flexible; physicians were told to increase the dose until symptoms remitted or side effects occurred.

"This was a forced titration. We started on 25 mg/day for a week, went to 50 mg/day the second week, sat there for a month, and then titrated up to 100 mg and 150 mg. As soon as we saw side effects, or if the child was in remission, we backed down."

After 12 weeks, the average daily sertraline dose in the combination group was 134 mg/day. In the sertraline-only group, two children withdrew from treatment because of an adverse effect. In the combination group, there were no adverse effect withdrawals. The drug was effective – 60% of children in the medication-only group improved significantly, as did 81% of those in the combination therapy group.

But the final sertraline dose was up to five times higher than the 25-37.5 mg/day dose commonly used in the psychiatric community, Dr. Walkup said. "At that low a dose, you’re going to have a lot of partial treatments and incomplete remissions. The kind of titration seen in the successful clinical trials pushes you to the highest safe dose, while most of what clinicians seek is the lowest effective dose. The problem with that is that you undershoot, undertreat, and leave kids crippled by partial recovery."

Dr. Walkup advises a literature review for physicians unfamiliar with forced titration of SSRIs. "Look at the trials and if you are not dosing in the time frame and dosages used in those trials, you are probably going too slow and too low. Think of where you should be before you call a drug a failure and stop it."

Another hurdle for some is off-label prescribing, he noted. The Food and Drug Administration has approved four SSRIs for obsessive-compulsive disorder and two for depression. But none of the drugs are approved for non–obsessive-compulsive disorder anxiety.

Despite the positive studies, "The chance that any of these drugs is ever going to be FDA-approved is slim to none," Dr. Walkup said. "So if you’re going to follow the evidence in treating childhood anxiety, you’re going to be prescribing off-label and you will have to be comfortable with that."

Dr. Walkup disclosed that he is a consultant for Shire Pharmaceuticals and has received research support from Abbott Laboratories, Lilly, and Pfizer.

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