Seriously Depressed Teens Respond to Combined Therapy

Over half of adolescents who don't respond to a first antidepressant improve when switched to a combination of a different antidepressant and cognitive-behavioral therapy (CBT). This is a key finding of an NIMH-funded clinical trial, the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA).

The combined therapy also produced a greater response than placing patients on another medication alone, suggesting that persistence may pay off in this population, said the authors in the February 27 Journal of the American Medical Association.

Previous trials have shown that SSRI antidepressants or CBT or the combination can produce an adequate clinical response in up to 60 percent of treated adolescents, the authors noted, but, “There are no empirical studies to guide clinicians regarding the management of adolescents with depression not responsive to an initial treatment with an SSRI.”

Previously, the Treatment of Adolescent Depression Study (TADS) demonstrated a similar benefit for combined therapy, but it tested a treatment-naïve group of depressed adolescents. TORDIA differed in two ways from TADS. It was aimed at youth who had not responded to a first round of treatment, and it included more chronically depressed adolescents (averaging two years) and more with suicidal ideation (59 percent)—groups often excluded from clinical trials, said lead author David Brent, M.D., in an interview with Psychiatric News.

“This was a much more difficult-to-treat sample,” said Brent, a professor of psychiatry at the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic. “We came to see that it would be unethical not to study people at high risk.”

The TORDIA study recruited young people, aged 12 to 18, who had not responded to at least an eight-week regimen of an SSRI antidepressant and who were not receiving CBT. In all, 334 patients at six institutions were randomized to one of four treatment options: a new SSRI alone (fluoxetine, paroxetine, or citalopram); an SSRI along with CBT; venlaflaxine with CBT; and venlaflaxine alone. Venlaflaxine, an SSRI/SNRI, was included because it has shown value in some trials in adults, said the authors.

The FDA's black-box warning, issued in the midst of the trial, may have cut into recruitment efforts, but may also have prompted improved procedures for monitoring any emergence of suicidal ideation or behavior and helped to fine-tune rescue protocols for intervention if signs of suicidality appeared, said Brent.

About 86 percent of the participants completed 12 weeks of the treatment protocol. Those who left did so because of adverse effects, nonadherence or withdrawal of consent, or need for out-of-protocol treatments. Participants were mostly white (82 percent), female (70 percent), and middle class ($61,000 annual median family income). However, compared with other trials, such as TADS, participants showed higher rates of two risk factors—chronicity and suicidal ideation—that made this sample more like the patients seen in routine community practice.