Analysis of data from the Treatment for Adolescents With Depression
Study (TADS) indicates that treatment with a selective serotonin reuptake
inhibitor (SSRI) or a combination of an SSRI and cognitive-behavioral therapy
are cost-effective at 12 weeks of treatment. The researchers concluded,
however, that based on a standard cost-effectiveness measure, SSRI treatment
is more cost-effective than combination therapy since the additional
improvement came at a high cost.
The TADS study, sponsored by the national Institute of Mental Health to
determine the best way to treat teenagers with major depression, earlier
reported that therapy combining the SSRI fluoxetine with cognitive-behavioral
therapy (CBT) produced better clinical outcomes than did placebo or either
At 12 weeks, 73 percent of patients in TADS receiving combination therapy,
62 percent of those receiving fluoxetine only, 48 percent of those receiving
CBT alone, and 34 percent of those receiving placebo were considered treatment
Over the 12-week study, patients on placebo accrued median costs of $841,
those taking fluoxetine alone $942, patients on CBT alone $2,287, and those on
a combination of the drug and CBT $2,832. Each category, however, had
wide-ranging costs. For instance, placebo costs ranged from $109 to $23,838
per patient, and combination therapy cost between $390 and $15,292 per
The study was posted on AJP In Advance on April 15 and will be
published in the May print edition of the American Journal of
In an editorial accompanying the article, Grayson Norquist, M.D., professor
and chair of the Department of Psychiatry and Human Behavior at the University
of Mississippi, pointed out some of the study limitations—most notably
that looking at cost-effectiveness at 12 weeks may be premature, given that it
takes weeks and sometimes months for treatment to begin alleviating
The cost-effectiveness study was conducted by Marisa Elena Domino, Ph.D.,
an associate professor of health policy and administration in the School of
Public Health at the University of North Carolina at Chapel Hill, and
"The implication of these results is that fluoxetine is more
cost-effective based on short-term outcomes; combination therapy would only be
recommended over fluoxetine if the additional clinical improvement is worth
the markedly higher costs," wrote Domino and colleagues.
The authors noted several limitations. For example, "This study did
not separately incorporate either suicidal behavior or other adverse effects
into the cost-effectiveness analysis, although clearly the costs of suicidal
behavior in youth are tremendous."
The study was a useful step and a valuable way to think about clinical
trials' outcomes, said Robert Rosenheck, M.D., a professor of psychiatry and
epidemiology and public health and director of the Division of Mental Health
Services and Outcomes Research at Yale University and the Department of
Veterans Affairs Medical Center in West Haven, Conn.
However, he was also concerned that the study might nudge insurance
companies to stop reimbursing for psychotherapy, a step he thought was
"One small study should not set policy," he told
Psychiatric News. "Psychotherapy is a human service, and it
takes time and professional skills to carry it out, so it's
The study included data from 369 of the 439 young people aged 12 to 18 in
the original TADS study (Psychiatric News, September 3, 2004). The
researchers added up costs for CBT, medications and medication management,
time and travel, and other services. Costs could also include inpatient
medical or psychiatric treatment, case management, drug or alcohol
detoxification, emergency room visits, or other needed services.
Depression-free days, which were determined from the Children's Depression
Rating Scale-Revised were translated into quality-adjusted life years (QALY),
a standard measure of cost-effectiveness. Participants averaged 22
depression-free days in the first 12 weeks of treatment.
Results indicated that using fluoxetine treatment alone improved clinical
outcomes at only a slightly higher cost than placebo.
"CBT was neither an effective nor cost-effective option at 12
weeks," wrote the authors. "Combination therapy had the highest
costs, but [showed] the greatest [clinical] improvements... and should be
considered cost-effective at $123,000 per QALY."
However, using combination treatment raised the cost per additional QALY to
In his editorial, Norquist argued for caution in interpreting these
results. He noted that the costs attributed to placebo were in part a result
of the trial design because they included time, travel, and services to"
manage" the nondrug costs that would not exist for patients on no
treatment at all. That, wrote Norquist, "exaggerates the
cost-effectiveness difference between drug alone and combination
Further, the fact that the study period was only 12 weeks "highlights
the problem of basing cost-effectiveness on short-term data for conditions
likely to be chronic and in need of long-term interventions that have variable
effects over time on health and functional status," wrote Norquist.
Both Norquist and Domino said that results of TADS at 36 weeks showed
similar improvement with fluoxetine alone and CBT alone. By that time, all
results clustered closer than at 12 weeks. Positive response rates were 86
percent for combination therapy, 81 percent for fluoxetine alone, and 81
percent for CBT alone.
"If long-term costs are proportional to those in stage 1, the later
CBT response could mean that CBT should become more cost-effective..,"
The absence of an overwhelming difference in response over a longer term
muddies the water for determining cost-effectiveness, said Rosenheck.
"Even if the science were totally clear, it isn't clear what we
should do about it," he said. "The science of cost-effectiveness
and effective policies will evolve together, but we are still at the beginning
of the process." ▪