|Teens with Treatment-resistant Depression More Likely to Get Better with Switch to Combination Therapy
Teens with difficult-to-treat depression [http://www.nimh.nih.gov/health/topics/depression/depression-in-children-and-adolescents.shtml]
who do not respond to a first antidepressant medication are more
likely to get well if they switch to another antidepressant medication
and add psychotherapy rather than just switching to another antidepressant,
according to a large, multi-site trial funded by the National Institutes
of Health's National Institute of Mental Health (NIMH). The
results of the Treatment of SSRI-resistant Depression in Adolescents
(TORDIA) trial were published February 27, 2008, in the Journal
of the American Medical Association (JAMA).
"The findings should be encouraging for families with a
teen who has been struggling with depression for some time," said
lead researcher David Brent, M.D., of the University of Pittsburgh. "Even
if a first attempt at treatment is unsuccessful, persistence will
pay off. Being open to trying new evidence-based medications or
treatment combinations is likely to result in improvement."
Adolescents with treatment-resistant depression have unique needs,
for which standard treatments do not always work.
"About 40 percent of adolescents with depression do not
adequately respond to a first treatment course with an antidepressant
medication, and clinicians have no solid guidelines on how
to choose subsequent treatments for these patients," said
NIMH Director Thomas R. Insel, M.D. "The results from TORDIA
bring us closer to personalizing treatment
for teens who have chronic and difficult-to-treat depression."
Brent and colleagues conducted TORDIA at six regionally dispersed
clinics with 334 adolescents ages 12
to 18. The teens in the study all had major depression and had
not responded to a previous two-month course of a selective serotonin
reuptake inhibitor (SSRI), a type of antidepressant. The teens
were randomly assigned to one of four interventions for 12 weeks:
- Switch to
another SSRI — paroxetine (Paxil), citalopram (Celexa)
or fluoxetine (Prozac)
to a different SSRI plus cognitive behavioral therapy (CBT),
a type of psychotherapy that emphasizes problem-solving and behavior
- Switch to
venlafaxine (Effexor) — another type of antidepressant
called a serotonin and norepinephrine reuptake inhibitor (SNRI)
- Switch to
venlafaxine plus CBT
The researchers chose to compare SSRIs with an SNRI because some
studies on adults have found that venlafaxine is more effective
than an SSRI in managing treatment-resistant depression.
About 55 percent of those who switched to either type of medication
and added CBT responded, while 41 percent of those who switched
to another medication alone responded. There were no differences
in response between those who switched to an SSRI and those who
switched to an SNRI, nor were there differences in response among
the three SSRIs tested.
Unlike similar studies on adolescent depression, TORDIA did not
exclude teens who were thinking about
suicide or had attempted suicide. They were included so that TORDIA
would mirror real-world treatment situations, and its findings
would be readily applicable to community settings.
More than half of the participants expressed suicidal thinking
and behavior (suicidality) before treatment began, and all teens
were monitored weekly for side effects related to suicidality and
predictive symptoms like hostility and irritability.
None of the TORDIA treatment groups, however, showed any measurable
effects on suicidality, a finding consistent with other studies
that have discovered suicidality does not necessarily subside when
the depression does. The researchers reiterated the need for new
treatments that specifically prevent or alleviate suicidality.
Although none of the medications seemed to be superior over the
others, venlafaxine was associated with more adverse effects, such
as skin infections and cardiovascular side effects. The researchers
concluded that because venlafaxine had a greater potential for
side effects, switching to another SSRI should be considered first.
The findings echo those of the NIMH-funded Treatment for Adolescents
with Depression Study (TADS), [http://www.nimh.nih.gov/health/trials/practical/tads/index.shtml]
which concluded that depressed teens benefited most from a combination
of medication and psychotherapy over both the short and long terms.
They are also consistent with results from the NIMH-funded Systematic
Treatment Alternatives to Relieve Depression (STAR*D) [http://www.nimh.nih.gov/health/trials/practical/stard/index.shtml]
study, which showed that adults with persistent
depression can get well after trying several treatment strategies.
The National Institute of Mental Health (NIMH) mission is to reduce
the burden of mental and behavioral disorders through research
on mind, brain, and behavior. More information is available at
the NIMH website, http://www.nimh.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
Brent D, et al. The treatment of adolescents with SSRI-resistant
depression (TORDIA): A comparison of switch to venlafaxine or to
another SSRI, with or without additional cognitive behavioral therapy. Journal
of the American Medical Association. 2008 Feb 27.