Within one year after active interventions ended, adolescents who
participated in the Treatment for Adolescents With Depression Study (TADS)
largely retained the improvements they evidenced during the study and saw
minimal symptom deterioration, a recent analysis conducted by the TADS
In findings published online September 1 in AJP in Advance, the
TADS researchers reported the long-term outcomes of youth with major
depressive disorder who had been treated with combined fluoxetine and
cognitive-behavioral therapy (CBT), fluoxetine alone, or CBT alone for 36
weeks. After the study-related treatments ended, the clinical benefits the
subjects achieved during active treatment were retained similarly across all
treatment groups (see
The multisite TADS trial, which began in 1999, was funded by the National
Institute of Mental Health (NIMH). During the active-treatment phases of the
trial, 327 adolescents aged 12 to 17 with a diagnosis of major depressive
disorder were first randomized to acute treatments with fluoxetine, CBT, or
both modalities combined for 12 weeks, followed by an additional 24 weeks of
open-label, continued treatment. At the end of the 36 weeks of active
treatments, 215 patients participated in follow-up assessments every three
months, and those who showed signs of relapse were referred to a clinician in
the community for additional treatment.
During the yearlong follow-up, 2.8 percent of the patients had a
psychiatric-related hospitalization, and about one-third received outpatient
mental health care on their own.
A small minority (13 percent) of the study patients were judged to have
experienced clinical deterioration during this follow-up period by independent
evaluators using the Clinical Global Impression (CGI) scale. Of the subgroup
of patients who were in remission at the end of the 36-week active treatment,
about 30 percent failed to meet the definition of remission at some point
during the one-year follow-up. The three acute-phase treatment groups did not
differ significantly on these long-term outcomes.
The finding that most adolescent patients with depression maintained their
clinical response after 36 weeks of active treatment contrasts with a
short-term study published in the April 2008 American Journal of
Psychiatry. In that study, patients aged 7 to 18 who had achieved
clinical response after 12 weeks of acute fluoxetine treatment for major
depressive disorder were then randomly assigned to either fluoxetine or
placebo. During the next six months, 69 percent of patients on placebo and 42
percent who continued on fluoxetine relapsed; the rates were statistically
significantly different. The TADS authors also pointed to previous
epidemiological and intervention studies showing a relapse rate of 25 percent
to more than 50 percent after children and adolescents recovered from a
The relatively high rate of sustained response and low rate of relapse seen
in TADS patients is encouraging, but the reason for this favorable outcome is
yet to be fully understood.
"There are two explanations for the findings," John March,
M.D., M.P.H., the principal investigator of TADS, told Psychiatric
News. He is the director of the Neurosciences Medicine Division at Duke
Clinical Research Institute and a professor of psychology and neuroscience at
Duke University. "One explanation is that long-term treatment produces
sustained response and remission. The other is that [the sustained response]
may reflect sample attrition, as only the sustained remitters stayed in the
study," said March.
March cowrote a review of the overall results from TADS so far with
Benedetto Vitiello, M.D., chief of the Child and Adolescent Treatment and
Preventive Intervention Research Branch at NIMH, which summarized key clinical
messages gleaned from the study. The review was also published in AJP in
Advance on September 1 and, along with the follow-up study, in the
October print edition of the American Journal of Psychiatry.
Among the clinical messages derived from the study data, March and Vitiello
noted, is that "it appears that six to nine months of treatment likely
will be adequate for the average patient." Although only 23 percent
reached remission at week 12—the end of the acute treatment—the
remission rate went up to more than 50 percent by week 36 in all three
treatment groups (55 percent for fluoxetine alone, 64 percent for CBT alone,
and 60 percent for combined CBT and fluoxetine).
In addition to showing the benefits that accrue from treating patients
beyond 12 weeks, TADS also revealed several advantages of combined treatment
over using CBT or fluoxetine monotherapy, according to March and Vitiello. For
example, although combination treatment did not beat either monotherapy in
response rate, patients on combination treatment reached maximum symptom
improvement at week 18, on average three months earlier than those on either
CBT or fluoxetine alone.
Another notable finding was that adolescents were twice as likely to have
suicidal ideation or behaviors if they were treated with fluoxetine only than
if they received CBT only or combination therapy. In fact, CBT appeared to
have a protective effect on suicidality, since the rate of suicidal ideation
or behaviors was significantly higher in the fluoxetine-only group, but
similar between the CBT-only and combination therapy groups.
"The Treatment for Adolescents With Depression Study (TADS):
Outcomes Over 1 Year of Naturalistic Follow-Up" is posted at<ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2009.08111620v1>."
Clinical Messages From the Treatment for Adolescents With Depression
Study (TADS)" is posted at<ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2009.08101606v1>."
Fluoxetine Versus Placebo in Preventing Relapse of Major Depression in
Children and Adolescents" is posted at<ajp.psychiatryonline.org/cgi/reprint/165/4/459>.▪