Adolescents with depression who have not responded to initial treatment with a selective serotonin reuptake inhibitor (SSRI) may have more effective results by changing medication and beginning cognitive behavioral therapy. According to an article in the February 27, 2008 issue of JAMA, this improves symptoms in comparison with just changing the medication.
Adolescent depression is condition that is common, chronic, recurrent and ultimately impairing. The researchers explain, “Untreated depression results in impairment in school, interpersonal relationships, occupational adjustment, and increases the risk for suicidal behavior and completed suicide. Therefore, the proper treatment of adolescent depression has profound public health implications for youth in this critical stage of development.”
SSRIs are a family of antidepressants that are typically used for depression and anxiety. They function by preventing reabsorption of the neurotransmitter seratonin into the presynaptic neuron. This increases seratonin levels between the neurons, thereby increasing the amount of seratonin that is absorbed into the postynaptic cell. In adults, the antidepressant venlafaxine, a selective serotonin and noradrenergic reuptake inhibitor (SNRI) has been shown to be effective in treatment-resistant depression.
Standard clinical guidelines for treatment of adolescent depression indicate prescription of SSRI medications, psychotherapy, or both. These treatments, either alone or on combination, have been shown to be effective, but at least 40% of adolescents with depression do not display adequate clinical response to these treatments.
David Brent, M.D., of the University of Pittsburgh, and colleagues compared the relative efficacy of various treatments for resistant adolescent depression, taking into account medication type, cognitive behavioral therapy (CBT), and the combination of the two. In a randomized controlled trial conducted between 2000 and 2006, 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder who showed insufficient response to a two-month initial treatment with an SSRI were analyzed. Participants were randomized to one of four treatments over 12 weeks: a switch to a second, different SSRI (either paroxetine, citalopram, or fluoxetine); a switch to a different SSRI plus CBT; a switch to venlafaxine; or a switch to venlafaxine plus CBT.
The authors reported that while the differences between the two new types of medications were negligible, the combination of a new antidepressant and CBT was effective. “In this study of adolescents with moderately severe and chronic depression who had not responded to an adequate course of treatment with an SSRI antidepressant, switching to a combination of CBT and another antidepressant resulted in a higher rate of clinical response [54.8 percent] than switching to another medication without CBT [40.5 percent]. There was no differential effect between switching to another SSRI [47.0 percent] or to venlafaxine [48.2 percent].”
There were no differential effects based on treatment in self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or other adverse events. During venlafaxine treatment, there was a greater increase in diastolic blood pressure and pulse, and more frequent occurrences of skin problems than with SSRI treatments.
The researchers conclude that there is hope for the adolescent with depression, even after an unsuccessful initial treatment. “… the clinician should convey hope to the adolescent with depression and his or her family that, despite a first unsuccessful treatment for depression, persistence with additional appropriate interventions can result in substantial clinical improvement.”
Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression
David Brent, MD; Graham Emslie, MD; Greg Clarke, PhD; Karen Dineen Wagner, MD, PhD; Joan Rosenbaum Asarnow, PhD; Marty Keller, MD; Benedetto Vitiello, MD; Louise Ritz, MBA; Satish Iyengar, PhD; Kaleab Abebe, MA; Boris Birmaher, MD; Neal Ryan, MD; Betsy Kennard, PsyD; Carroll Hughes, PhD; Lynn DeBar, PhD; James McCracken, MD; Michael Strober, PhD; Robert Suddath, MD; Anthony Spirito, PhD; Henrietta Leonard, MD; Nadine Melhem, PhD; Giovanna Porta, MS; Matthew Onorato, LCSW; Jamie Zelazny, MPH, RN
JAMA. 2008;299(8):901-913.
Written by Anna Sophia McKenney