Cognitive-behavioral therapy (CBT), whether combined with fluoxetine or
placebo, is highly effective in treating major depressive disorder in
adolescents who also have a substance use disorder (SUD) and conduct disorder,
according to a randomized, double-blind study by researchers from the
University of Colorado at Denver.
While medication was a little more effective than placebo in reducing
depressive symptoms, giving a placebo along with weekly CBT sessions designed
to treat substance use problems worked almost as well.
The authors, led by Paula Riggs, M.D., an associate professor at the
Department of Psychiatry at the University of Colorado, enrolled 126
adolescents between 13 and 19 years old who were diagnosed with major
depression as well as SUD and conduct disorder. Based on the participating
physicians' overall assessment, 67 percent of the 63 patients in the
placebo-plus-CBT group and 76 percent of the 63 patients in the
fluoxetine-plus-CBT group were deemed "very much improved" or"
much improved" after being treated for four months.
The difference in effectiveness between fluoxetine and placebo was not
statistically significant in terms of physicians' ratings of symptom
improvement, but was statistically significant in scores of the Childhood
Depression Rating Scale—Revised (CDRS-R), an overall rating of
depression severity based on a clinician-conducted, semistructured interview
with the patient. About 69.8 percent of patients in the fluoxetine-CBT group
and 52.4 percent of the placebo-CBT group reached remission for their
depression (defined as CDRS-R score of 28 or less); this difference did not
reach statistical significance.
Some study participants were recruited from the social-service and
juvenile-justice systems. The authors pointed out that most large, controlled
clinical trials of antidepressants in young patients exclude those with
substance use disorders despite the high rates of comorbidity. Because of the
lack of research data, "clinicians are often reluctant to prescribe
antidepressants for depressed adolescents with SUD" and "such
youths are...expected to complete substance treatment and achieve...abstinence
before antidepressant medication is considered."
The study was published in the November 2007 Archives of Pediatric and
Adolescent Medicine and was funded by National Institute on Drug Abuse
"Adolescents with major depression, substance abuse, and behavior
problems may be a clinically complex group, but unfortunately not an uncommon
one," said Christopher Kratochvil, M.D., a child psychiatrist at the
University of Nebraska Medical Center. "The investigators should be
congratulated for the clinically relevant and important work with this
understudied patient population."
According to survey data compiled by NIDA, the rate of illicit drug use
(use of such drugs at once within the prior month) in 2006 was 16.8 percent in
10th graders and 21.5 percent in 12th graders. Another study published in the
same issue of Archives of Pediatric and Adolescent Medicine by a
group of Massachusetts researchers found, through screening in the primary
care setting, that 14.8 percent of adolescents between ages 12 and 18 had
substance use problems. Many of these youths have comorbid psychiatric
disorders and have little access to mental health treatment until they are
picked up by the social-service or juvenile-justice systems, Riggs told
Psychiatric News. "About 80 percent of the study participants
were not court-mandated and came voluntarily, but they were just as sick [in
terms of] substance use disorders. They cannot afford treatment, and their
parents cannot afford it, and they haven't entered the social or
criminal-justice systems that pay for treatment."
The researchers were surprised by the high rates of treatment compliance
and completion by the youth in the study. Of the 126 participants, only six
were lost to follow-up, and two withdrew consent; 12 could not complete
because they went to jail or residential facilities, or moved out of the area."
It really begs the question of whether we as a society ought to offer
free treatment to these kids," said Riggs. "If you offer the
treatment, they will come."
In this study patients received weekly, standardized, one-hour CBT sessions
specifically targeting SUD, not depression. The youth learned cognitive and
behavioral techniques to better manage the negative thoughts and feelings that
can trigger substance use, with the goal of reducing such use. "It's
clear the coping skills, the empathic approach, the weekly monitoring...of CBT
were very effective," said Riggs. The high rates of response and
remission in the placebo-CBT group might have obscured the impact of
fluoxetine on depression, the authors suggested in their report.
The participants' self-reported frequency of substance use and conduct
disorder symptoms went down in both treatment groups during the study. The
placebo-CBT group actually improved a little more on average in terms of SUD
and conduct disorder outcomes than did the fluoxetine-CBT group, but the
differences were not statistically significant. "In the context of CBT
and controlling for fluoxetine use, we found that remission from depression
was a significant predictor of decreased substance use," said Riggs.
Riggs urged physicians to provide integrated, not sequential, treatment for
comorbid mental health issues and drug abuse problems. Adolescents with such
comorbidities responded to treatment in rates as high as those without these
comorbidities in depression studies, and the safety and efficacy of combined
CBT and fluoxetine were satisfactory, she pointed out.
This finding should convince clinicians not to wait for patients to stop
substance use before they initiate depression treatment. "Start with
CBT, but if they don't respond to the treatment in a month or so, physicians
shouldn't hesitate to add fluoxetine to treat the depression," she
An abstract of "A Randomized Controlled Trial of Fluoxetine
and Cognitive-Behavioral Therapy in Adolescents With Major Depression,
Behavioral Problems, and Substance Use Disorders" is posted at<archpedi.ama-assn.org/cgi/content/abstract/161/11/1026>.
An abstract of "Prevalence of Positive Substance Abuse Screen Results
Among Adolescent Primary Care Patients" is posted at<archpedi.ama-assn.org/cgi/content/abstract/161/11/1035>.▪