Most patients who achieved a sustained response to treatment in the first
12 weeks of the Treatment for Adolescents With Depression Study (TADS)
maintained their gains at 36 weeks, while over half of those who did not
achieve a sustained response at 12 weeks did so with further treatment,
according to the investigators' latest report.
Response was measured on the Clinical Global Impression-Improvement (CGI-I)
scale. Two consecutive ratings of 1 or 2 on the scale were considered a
The study adds further evidence to the value of longer-term treatment and
to the use of cognitive-behavioral therapy (CBT) added to or in combination
with an SSRI antidepressant (Psychiatric News, November 2, 2007).
In the trial's first three months, patients treated with fluoxetine alone
or in combination with CBT fared significantly better than those on CBT
monotherapy. However, at the end of 36 weeks, rates of sustained response to
fluoxetine alone, CBT alone, and combination therapy were about the same.
Thus, CBT appeared to take longer to achieve similar levels of efficacy,
compared with the other treatment conditions.
"These findings emphasize the value of ongoing treatment in
facilitating the depression recovery process," wrote clinical
psychologist Paul Rohde, Ph.D., senior research scientist at the Oregon
Research Institute in Eugene, and colleagues in the April Archives of
General Psychiatry. "Approximately three-quarters of adolescents
with depression who have not fully responded after 12 weeks of acute treatment
will experience sustained response with further
TADS was funded by the National Institute of Mental Health.
"This study adds some evidence to what we know from the overall TADS
study and the efficacy of fluoxetine," David Mrazek, M.D., told
Psychiatric News. "It supports current practice—that
medicine works, and that medicine in the context of a therapeutic relationship
works even better."
Mrazek, who was not involved with the TADS study, is chair of the
Department of Psychiatry and Psychology at the Mayo Clinic and a professor of
psychiatry at the Mayo Medical School in Rochester, Minn. He is also chair of
APA's Council on Children, Adolescents, and Their Families.
The results are also a reminder that treatment of adolescents for
depression can be a laborious process, Rohde told Psychiatric
"Clinicians have to educate patients and their parents that treatment
is effective but that it takes time to work," he said.
Researchers did not include patients randomized to placebo in the first 12
weeks of TADS. They tallied data for the 242 cases remaining in active
treatment arms at the start of stage 2. Patients continued on the same regimen
they used in the trial's first phase. Full responders were maintained at doses
of fluoxetine up to 40 mg/day, while partial responders had doses raised to 50
mg/day or 60 mg/day.
In stage 1, patients getting CBT received 15 sessions. In stage 2 (12 to 18
weeks), full responders in stage 1 got CBT every two weeks, while partial
responders received once-a-week therapy. During the third stage (18 to 36
weeks), patients saw a therapist at six-week intervals for three CBT booster
Full responders received CGI-I scores of 1 ("very much
improved") or 2 ("much improved"), while partial responders
had scores of 3 ("minimally improved"). All others were ranked as
About 82 percent, or 121, of the 147 patients with a sustained response at
the end of 12 weeks maintained that status through 36 weeks. While fewer
patients on CBT alone achieved full response by 12 weeks, the effect proved
highly durable. About 94 percent (30 out of 32) maintained their status,
compared with 70 percent of those on fluoxetine alone and 87 percent on
combination therapy. Rohde and his colleagues make no recommendations from
this finding, except to note that it is "promising and warrants further
investigation" in light of the small cohort involved.
The relatively poor showing of CBT in the first 12 weeks may not reflect on
the treatment itself, said Rohde. "It might have been unrealistic to
expect that 12 weeks of treatment would be adequate," he said. "If
these patients were treated for, say, 16 weeks, the results for CBT might have
Many of the 95 patients without a sustained response in the first phase of
the trial did achieve a sustained response by 36 weeks. These included 56.8
percent of those originally on CBT, 46.2 percent of those on fluoxetine, and
60 percent of those on combination therapy. The differences were not
statistically significant, according to the researchers.
The study gives some encouragement to continue treatment even if results
don't appear right away, said Mrazek. "It tells people who use CBT that
if it does work, it will tend to continue to work, and that's
However, maintaining consistency in the application of CBT across different
settings might be difficult, said Mrazek.
"It might be highly variable even at one site," he said."
Fluoxetine can be prescribed in reproducible doses, but therapists and
TADS recruited patients during 2000 to 2003. The researchers followed their
patients for a full year after the end of the 36-week active treatment trial
and will eventually report on how the effects of treatment persisted, said
Grants from the National Institute of Mental Health and the National
Institute on Drug Abuse will also allow them to track their subjects for five
years to record functional outcomes as they transition to college, young
adulthood, and the workplace
An abstract of "Achievement and Maintenance of Sustained
Response During the Treatment for Adolescents With Depression Study
Continuation and Maintenance Therapy" is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/65/4/447>.▪