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Switching Therapy for Adolescents With SSRI-Resistant Depression Better Than Changing Medication Alone, Pitt Researchers Report in JAMA

PITTSBURGH, February 26, 2008 — 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 published in the current issue of the Journal of the American Medical Association. However, 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, M.D., academic chief of child and adolescent psychiatry at Western Psychiatric Institute & Clinic and professor of psychiatry, pediatrics and epidemiology at the University of Pittsburgh School of Medicine. “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 non-response 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.”

Dr. Brent and his team of researchers created a six-site, National Institutes of Mental Health funded study, the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA), in order to focus on non-response to an SSRI, rather than on non-response 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, an SNRI (serotonin and norepinephrine reuptake inhibitor), 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 Dr. 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, Ph.D., professor and chair of statistics in the University of Pittsburgh’s School of Arts and Sciences. Inconsistencies among the six reporting sites could derail a project, said Dr. Iyengar, who has worked with Dr. Brent and others in the psychiatry department for more than 20 years as a research statistician. Iyengar participated in TORDIA’s initial planning and execution, for example, by ensuring that important patient characteristics were balanced across treatments so that the data from the sites would generate a consistent conclusion. Afterward, he and statisticians in Pitt’s Department of Statistics and at WPIC did the analysis of the data, conducted statistical analyses and examined common and unique effects across sites.

Co-authors of the study include Boris Birmaher, M.D., Neal Ryan, M.D., Nadine Melhem, Ph.D., Giovanna Porta, M.S., Matthew Onorato, L.C.S.W., Kaleab Abebe, M.A., and Jamie Zelanzy, M.P.H., R.N., University of Pittsburgh; Graham Emslie, M.D., and Betsy Kennard, Psy.D., University of Texas Southwestern Medical Center; Greg Clarke, Ph.D., and Lynn DeBar, Ph.D., Kaiser Permanente, Portland, Ore.; Karen Dineen Wagner, M.D., Ph.D., University of Texas Medical Branch; Joan Asarnow, Ph.D., James McCracken, M.D., Michael Strober, Ph.D., and Robert Suddath, M.D., University of California, Los Angeles; Marty Keller, M.D., Anthony Spirito, Ph.D., and Henrietta Leonard, M.D., Brown University; Ben Vitiello, M.D., and Louise Ritz, Ph.D., National Institutes of Mental Health.

The University of Pittsburgh School of Medicine is one of the nation’s leading medical schools, renowned for its curriculum that emphasizes both the science and humanity of medicine and its remarkable growth in National Institutes of Health (NIH) grant support, which has more than doubled since 1998. For fiscal year 2006, the University ranked sixth out of more than 3,000 entities receiving NIH support with respect to the research grants awarded to its faculty. The majority of these grants were awarded to the faculty of the medical school. As one of the university’s six Schools of the Health Sciences, the School of Medicine is the academic partner to the University of Pittsburgh Medical Center. Their combined mission is to train tomorrow’s health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care.

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