NEW YORK – Cognitive-behavioral therapy seems to ramp up the beneficial effect of antidepressant treatment for children and teens.
About 60% of youngsters will respond favorably to their first antidepressant medication – generally a selective serotonin reuptake inhibitor (SSRI), Dr. Karen D. Wagner said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
Dr. Karen Wagner
Switching to a different antidepressant will help about 50% of those who don’t respond. But adding psychotherapy will grab about 10% more – bringing the total response rate up to around 70%, said Dr. Wagner of the University of Texas Medical Branch, Galveston.
The landmark TORDIA (Treatment of Resistant Depression in Adolescents) study showed very clearly that piggybacking both treatments is more effective than using medication alone (JAMA 2008;299:785-92).
The study was published in 2008 but remains a key piece of clinical evidence for helping youngsters with treatment-resistant depression. It included about 300 teens who failed their initial 8-week SSRI therapy. They were then randomized to 12 weeks of switching to a different SSRI alone; switching to venlafaxine alone; or switching to either of the drugs plus cognitive-behavioral therapy (CBT).
Adding CBT to either medication showed a higher response rate (55%) than did the medication alone (40%). The new drugs alone were equally effective (new SSRI, 47%; venlafaxine, 48%).
TORDIA could give the impression that psychotherapy might be the best choice for initial treatment, Dr. Wagner said. While it is a great add-on, the timing of CBT response is a big consideration.
"CBT certainly increases the pool of patients who will respond, but it is not as effective initially as medication. CBT eventually does catch up, but if you have a child with moderate to severe depression, the question is: Do we have the time for that? I tend to encourage parents to think about medication first if we don’t have many months to wait for a child to get well."
Choosing among off-label medications
Venlafaxine is one of many antidepressants that are not approved for use in children and teens. Treating depression in youngsters almost always means off-label prescribing. Only two antidepressants – fluoxetine and escitalopram – are Food and Drug Administration–approved for children and teens, and only fluoxetine is approved for children younger than 12 years. And data are actually mixed about fluoxetine; a recent published study showed it was no different from placebo over 6 months.
Of the older, more well-known antidepressants, only two have positive data for youngsters. One randomized study of citalopram posted positive findings for its primary endpoint (Am. J. Psychiatry 2004;161:1079-83). The other is sertraline, which had positive overall findings in a pooled analysis, although the individual studies were negative (JAMA 2003;290:1033-41).
Studies on all of the other drugs were negative, including mirtazapine (two studies), nefazodone (two), paroxetine (three), and venlafaxine (two). This doesn’t mean the medications won’t work – they do benefit some children, Dr. Wagner said. But parents need to know that the studies in children were not positive. However, she added, the safety profiles were all reasonably good.
There are no pediatric safety or efficacy data on any of the new antidepressants. That list includes vilazodone, desvenlafaxine, levomilnacipran, vortioxetine, as well as the less-traditional choices of l-methylfolate and ketamine.
"When you’re thinking about a treatment algorithm, these should be very, very low on the list," Dr. Wagner said. "And make sure to let parents know there are some safety and efficacy data in adults, but they have never been studied in children or adolescents."
Duloxetine disappoints in latest studies
The newest evidence for duloxetine in youngsters with depression looks lousy.
In two highly anticipated, yet-unpublished, phase III trials, duloxetine and fluoxetine – which is already approved for kids – completely fell apart relative to placebo, Dr. Wagner said.
The studies were both sponsored by Eli Lilly; they comprised a total of about 1,000 children and teens. Both included 10-week acute treatment phases followed by 6-month extensions.
The first study randomized patients to up to 120 mg of duloxetine, up to 40 mg of fluoxetine, or placebo for 10 weeks. After that, those who were taking placebo crossed over to up to 120 mg of duloxetine for 6 months. The other regimens remained stable.
By 10 weeks, the mean decrease in the Children’s Depression Rating Scale was 24.3 points for duloxetine, 23.7 points for fluoxetine, and 24.3 points for placebo. By 36 weeks, the CDRS for children still taking duloxetine had decreased another 7 points. It decreased by an additional 9.9 points in those who continued fluoxetine, and by 9.6 points in those who crossed over to duloxetine. None of the between-group differences were significant.