Depression in Adolescents: Treatment Dilemma
Major Depressive Disorder is a common condition in adolescents. The estimated prevalence of depressive disorders in this age group is 5% and it results in high morbidity including psycho-social and developmental disruption as well as a significant increased risk for suicide. Improved treatment for this disorder has profound implications both for the children suffering from the disorder and for public health.
The best study ever conducted in the field of Child and Adolescent Psychiatry to evaluate the efficacy of antidepressant medications and cognitive behavioral therapy in adolescents was published in JAMA in August 2004. Referred to as the TADS (Treatment for Adolescents with Depression Study), it was a multi-center, randomized and controlled study that evaluated 439 patients between the ages of 12-17 with major depressive disorder. The four arms of the 12-week study included the following groups: 1. fluoxetine (prozac) alone—titrated from 10mg up to 40 mg; 2. cognitive behavior therapy (CBT) alone; 3. CBT + fluoxetine; and 4. placebo. Patients at high risk for suicide were excluded, but approximately 30% of the patients had some evidence of suicidal ideation.
CBT has well-documented efficacy for the treatment of adolescent and adult depression, as well as for the treatment of other conditions such as panic disorder and OCD. In this study, the CBT component consisted of 15 sessions with psycho-education, cognitive restructuring of thought patterns and social problem-solving.
The study found that after twelve weeks of therapy all patients had a decrease in depressive symptoms. The greatest improvement was seen in the group that received combined treatment with fluoxetine + CBT with 71% of patients improving based on the Children’s Depression Rating Scale-Revised (CDRS-R). Fluoxetine alone proved to be superior in treatment response (60.6%) to CBT alone (43.2%) as well as to placebo (34.8%).
At the time of the study, fluoxetine was the only anti-depressant medication FDA-approved for use in the treatment of adolescent depression—even though several other SSRI medications including Zoloft and Celexa are commonly prescribed in practice. No previous study has shown so robust a response rate in children or teenagers to anti-depressant medications.
Prior research has documented CBT response rates consistently as high as 60%. The relatively low response rate reported here may be attributable to the fact that this study included patients with more chronic and/or more severe depression (compared to most studies), and that CBT’s benefit is often most pronounced over time rather than in the acute phase of treatment. Interestingly, there are always high placebo response rates in depression treatment studies of children as well as adults that may suggest some intrinsic benefit from contact with a mental health clinician and brief monitoring alone.
No adolescents in the study completed suicide, although there was a slight increased rate of expressed suicidal ideation in those patients on active medication. CBT appeared to have a protective effect to decrease suicidal behavior. Whether SSRI treatment is associated with an emergence of suicidal thinking is still controversial and unclear. Over weeks of treatment, and with symptom improvement, suicidality is significantly diminished.
The choice of the best treatment has been confusing for physicians, especially in light of the FDA decision mandating that all antidepressants include a black box warning statement that antidepressants increase the risk of suicidal ideation and behavior in children and adolescents. However, MDD is one of the largest risk factors for suicide so effective diagnosis and treatment is essential. The importance of TADS is that it demonstrates a robust finding as to the efficacy of anti-depressant medication in the treatment of adolescent depression. Evidence-based therapy, premised on the results of well-conducted research protocols, should be the basis of best practice guidelines.
The current recommendation of the American Academy of Child and Adolescent Psychiatry is that combined therapy with an antidepressant medication and psychotherapy is the most effective treatment for moderate to severe depression in adolescence.
JAMA, August 18, 2004—Vol 292, No. 7
This information provided by Robert A. Root, M.D., Medical Directory, Child and Adolescent Psychiatry, California Pacific Medical Center Department of Pediatrics.