Aug. 16, 2004 — Adolescents with major depressive disorder showed improvement
after treatment that combined fluoxetine (an antidepressant medication) and
cognitive behavioral therapy (CBT), according to the results of the Treatment
for Adolescents with Depression Study (TADS) published in the Aug. 18 issue of
the Journal of the American Medical Association (JAMA).
According
to background information in the article, major depressive disorder (MDD) is
common in adolescence. "...depression in adolescence is a major risk factor for
MDD, suicide, and long-term psycho-social impairment in adulthood. Thus,
improvements in the treatment of MDD among adolescents should positively affect
public health."
John S. March, M.D., M.P.H., from Duke University Medical
Center in Durham, N.C., and colleagues from the TADS team, evaluated the
effectiveness of four treatments among adolescents with MDD. This study included
439 patients with a primary diagnosis of MDD who ranged in age from 12 to 17
years. They enrolled in the study between spring 2000 and summer 2003 at 13
academic and community clinics across the United States. The participants were
randomly assigned to twelve weeks of fluoxetine alone, CBT alone, CBT with
fluoxetine, or placebo (sugar pill). "In TADS, CBT is a skills-oriented
treatment based on the assumption that depression is caused by or maintained by
depressive thought patterns and a lack of active, positively reinforcing
behavioral patterns; treatment included 15 sessions, which lasted between 50 and
60 minutes, over the first 12 weeks," the authors describe.
"Compared
with fluoxetine alone and CBT alone, treatment [combining] fluoxetine with CBT
was superior," the authors report. "Fluoxetine alone is a superior treatment to
CBT alone. Rates of response for fluoxetine with CBT were 71 percent; fluoxetine
alone, 60.6 percent; CBT alone, 43.2 percent; and placebo, 34.8 percent. ...
Clinically significant suicidal thinking, which was present in 29 percent of the
sample at baseline, improved significantly in all four treatment groups.
Fluoxetine with CBT showed the greatest reduction. Seven (1.6 percent) of 439
patients attempted suicide; there were no completed suicides." The researchers
also found treatment with fluoxetine alone elevated the risk for psychiatric
adverse events. "While fluoxetine did not appear to increase suicidal ideation
(thoughts), harm-related adverse events may occur more frequently in
fluoxetine-treated patients and CBT may protect against these events," the
researchers add.
In conclusion the authors write: "First, given the high
prevalence, morbidity, and significant mortality associated with MDD, the
identification of depressed adolescents and provision of evidence-based
treatment should be mandatory in health care systems. Second, despite calls to
restrict access to medications, medical management of MDD with fluoxetine,
including careful monitoring for adverse events, should be made widely
available, not discouraged. Third, given incremental improvement in outcome when
CBT is combined with medication and, as importantly, increased protection from
suicidality, CBT also should be readily available as part of comprehensive
treatment for depressed adolescents."
Editor's Note: The research for
this article was supported by a contract from the National Institute of Mental
Health. Lilly Inc. provided fluoxetine and matching placebo under an independent
educational grant to Duke University. Please see JAMA study for authors'
financial disclosures.
Editorial: Treatment of Adolescents with Major
Depression
In an accompanying editorial, Richard M. Glass, M.D.,
Deputy Editor, JAMA, and the Department of Psychiatry, University of Chicago,
writes, "the publication of the results of the Treatment for Adolescents With
Depression Study (TADS) in this issue of JAMA is certainly timely in view of
recent and widely publicized controversies regarding treating adolescents with
depression.
"...the TADS results raise a mixture of questions and answers
regarding the complicated issue of whether antidepressant drug treatment
prescribed to treat depression might increase the risk for depression's most
dangerous outcome, suicidal behavior. The reduction of suicidal ideation over
time is reassuring, but the increased risk for harm-related adverse events
observed in the patients receiving fluoxetine suggests that the increase in
activation, irritability, or disinhibition sometimes associated with SSRI
(selective serotonin reuptake inhibitor) treatment warrants careful monitoring
in clinical practice. However, the TADS results leave this as a question rather
than a firm answer because those specific symptoms were rare among the patients
receiving fluoxetine."
"Probably the most important message from TADS is
that carefully assessed, empirically validated treatments are available for
adolescents with major depression. A corollary of that message is that
depressive illness is a major public health problem with substantial morbidity
and mortality for adolescents as well as for adults. The results from this major
new trial demonstrate that although treatment of a depressive illness is often
successful and gratifying for patients and clinicians, such success typically
requires more than a brief visit for prescription of medication. Rather, it
requires careful assessment and monitoring in the context of an ongoing
patient-physician relationship. Furthermore, the current evidence suggests that
the likelihood of a good outcome is enhanced by the combination of appropriate
and carefully monitored drug treatment with an empirically validated
psychotherapy."
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