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David Baxter

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Drug-psychotherapy combination can help treatment-resistant depressed teens
February 27, 2008

More than half of teenagers with the most debilitating forms of depression that do not respond to treatment with selective serotonin reuptake inhibitors (SSRIs) show improvement after switching to a different medication combined with cognitive behavioral therapy, researchers at UT Southwestern Medical Center and their colleagues in a multicenter study have found.

"If an adolescent hasn't responded to an initial treatment, go ahead and switch treatments," said Dr Graham Emslie, professor of psychiatry and pediatrics at UT Southwestern and chief of child and adolescent psychiatry at Children's Medical Center Dallas, the study's principal investigator. "Our results should encourage clinicians to not let an adolescent stay on the same medication and still suffer."

The 334 study participants suffered from depression on average for about two years. The teenagers involved exhibited moderate to severe major depressive disorder, many with suicidal ideation. Historically, these types of patients have the worst treatment outcomes.

The researchers found that nearly 55 percent of teenagers who failed to respond to a SSRI, responded when they switched to a different antidepressant and participated in cognitive behavioral therapy, which examines thinking patterns to modify behavior.

The study also found that about 41 percent of participants responded after switching to either a different SSRI or to venlafaxine (Effexor?), a Serotonin-Norepinephrine Re-Uptake Inhibitor (SNRI).

SSRIs are the most common treatment for teenage depression, although previous studies have shown that about 40 percent of teenagers on the drugs don't respond to the first treatment.

"This is a group that has been suffering from a serious medical condition for a long time," said Dr Emslie, the first psychiatrist to demonstrate antidepressants are effective in depressed children and adolescents. "It's important that the adolescent not give up."

The Treatment of SSRI-resistant Depression in Adolescents (TORDIA) trial was conducted at six regionally dispersed clinics with 334 adolescents ages 12 to 18. The teens in the study all had major depression and had not responded to a previous two-month course of a selective serotonin reuptake inhibitor (SSRI), a type of antidepressant. The teens were randomly assigned to one of four interventions for 12 weeks:

  1. a different SSRI;
  2. a different SSRI plus cognitive behavioral therapy;
  3. venlafaxine only, or;
  4. venlafaxine plus cognitive behavioral therapy.
Improvement was measured using the Clinical Global Impressions Scale and Children's Depression Rating Scale-Revised.

The results showed that medication and therapy do not have to be independent of each other.

"If you haven't had a good response with antidepressants, definitely add cognitive behavioral therapy," Dr Emslie said. "Having them work together is probably the most beneficial."

Although none of the medications seemed to be superior over the others, venlafaxine was associated with more adverse effects, such as skin infections and cardiovascular side effects. The researchers concluded that because venlafaxine had a greater potential for side effects, switching to another SSRI should be considered first.

More than half of the participants expressed suicidal thinking and behavior (suicidality) before treatment began, and all teens were monitored weekly for side effects related to suicidality and predictive symptoms like hostility and irritability.

None of the TORDIA treatment groups, however, showed any measurable effects on suicidality, a finding consistent with other studies that have discovered suicidality does not necessarily subside when the depression does. The researchers reiterated the need for new treatments that specifically prevent or alleviate suicidality.

The study results are similar to research findings from the UT Southwestern-led STAR*D study on adult depression. The largest depression study of its kind, STAR*D has demonstrated that one in three to four adults who did not achieve full remission of symptoms from one antidepressant medication became symptom-free after changing or adding a second medication.

"One major question of psychiatrists is whether depression is different in adolescence," Dr Emslie said. "This research suggests this disease is present in adolescence and very similar to what happens in adulthood. It's important to identify and treat depression early."

"About 40 percent of adolescents with depression do not adequately respond to a first treatment course with an antidepressant medication, and clinicians have no solid guidelines on how to choose subsequent treatments for these patients," said Thomas R. Insel, MD, Director of the National Institute of Mental Health which funded the study. "The results from TORDIA bring us closer to personalizing treatment for teens who have chronic and difficult-to-treat depression."

Source: Brent D, Emslie G, Clarke G,. Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression: The TORDIA Randomized Controlled Trial. JAMA. 2008;299(8):901-913. [Abstract]
 

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