Pitt Study Assesses Options for Treatment-Resistant Depression in Teens

For depressed adolescents who have not responded to initial treatment with selective serotonin reuptake inhibitors (SSRIs), the combination of cognitive behavioral therapy (CBT) and a switch to another antidepressant had better clinical results than a change in medication without CBT, according to a study by University of Pittsburgh School of Medicine researchers.

The study is published in the current issue of the Journal of the American Medical Association. The study also found that a switch to another SSRI was just as effective as a switch to venlafaxine and resulted in fewer adverse side effects. Adolescent depression is a common, chronic, recurrent, and impairing condition that accounts for a substantial proportion of disability and mortality. Untreated depression results in problems in school and interpersonal relationships and increases the risk for suicidal behavior. Therefore, proper treatment has profound public health implications for youth in this critical stage of development.

“Current clinical guidelines for the acute management of adolescent depression recommend SSRIs coupled with CBT,” noted David A. Brent, professor of psychiatry, pediatrics, and epidemiology at Pitt’s School of Medicine and academic chief of child and adolescent psychiatry at Western Psychiatric Institute & Clinic (WPIC). While these treatments alone or in combination have been shown to be effective, previous studies have shown at least 40 percent of adolescents with depression do not respond sufficiently to these treatments. Despite the high percentage of nonresponse and the serious consequences of persistent depression in this age group, until now there have been no empirical studies to guide clinicians regarding the management of this population. With these results, doctors now have the guidelines to properly respond to and treat their adolescent patients.”

Brent and his team of researchers created a six-site, National Institutes of Mental Health-funded study called the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA). The study allowed researchers to focus on nonresponse to an SSRI rather than on nonresponse to psychotherapy, because SSRIs have been the predominant method of treatment for adolescent depression.

The study involved 334 depressed 12- to 18-year-olds who were followed for a period of 12 weeks. The effectiveness of four treatment strategies was evaluated in patients who had not responded to a two-month initial treatment with an SSRI. Those treatments included a switch to a second, different SSRI such as paroxetine, citalopram, or fluoxetine; a switch to a different SSRI in addition to CBT; a switch to venlafaxine; or a switch to venlafaxine in addition to CBT. Results showed CBT plus a switch to either medication regimen showed a higher response rate than a medication switch alone. However, there was no difference in response rate between venlafaxine and a second SSRI.

The researchers chose to compare SSRIs with venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), because prior studies on adults have shown that venlafaxine is more effective than an SSRI in managing treatment-resistant depression. And, unlike similar studies on adolescent depression, TORDIA included teens who were actively suicidal so that the study would mirror real-world treatment situations to ensure its findings would be readily applicable to community settings.

“These findings should be encouraging for families with a teen who has been struggling with depression for some time,” said Brent. Even if a first attempt at treatment is unsuccessful, persistence will pay off. Being open to trying new evidence-based medications or treatment combinations is likely to result in improvement.”

The large amounts of data in this study required regular monitoring and organization throughout its duration, explained chief statistician and co-author Satish Iyengar, professor and chair of statistics in the University’s School of Arts and Sciences.

Additional study coauthors in the Pitt School of Medicine included Boris Birmaher, professor of psychiatry; Neal Ryan, Joaquim Puig-Antich Professor in Child and Adolescent Psychiatry; and Nadine Melhem, assistant professor of psychiatry.

Other coauthors with Pitt affiliations included Giovanna Porta, systems analyst at WPIC; Matthew Onorato, project coordinator for the study at WPIC who is now at Nationwide Children’s Hospital in Columbus, Ohio; Kaleab Abebe, a statistics Ph.D. candidate in Pitt’s School of Arts and Sciences; and Jamie Zelazny, senior program coordinator for the study, who is now adverse events coordinator for Pitt’s Institutional Review Board.