Posted by Larry Hoover on August 26, 2004, at 13:32:28
One of the problems plaguing the interpretation of clinical studies involving adolescent and pediatric use of SSRIs is that the standardized reporting of potentially suicidal acts fell under the general heading "emotional lability", and some other things that fell under that same heading had nothing to do with suicidality at all. As a result, some reports linked SSRIs to suicidality when the evidence did not show that. In order to make sense out of this mess, the FDA commissioned two studies which "re-scored" the suicidal acts, using more explicit terms of reference. The new analyses do show an increase of suicidality for some drugs, but at a far lower extent than has been reported in the "shock media".
http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-11-TAB09a-Mosholder-review.pdf
Also, for the first time, suicidality is used as a primary outcome measure in a clinical trial of pediatric Prozac (fluoxetine). When suicidality is scored in this way, it is now clear that Prozac (at least) is not associated with an increase in suicidal thinking or acts. Quite the contrary.
Lar
JAMA. 2004 Aug 18;292(7):807-20.Comment in:
JAMA. 2004 Aug 18;292(7):861-3.
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial.March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J; Treatment for Adolescents With Depression Study (TADS) Team.
Duke Clinical Research Institute, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. jsmarch@acpub.duke.edu
CONTEXT: Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI). However, little is known about their relative or combined effectiveness. OBJECTIVE: To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of a volunteer sample of 439 patients between the ages of 12 to 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder. The trial was conducted at 13 US academic and community clinics between spring 2000 and summer 2003. INTERVENTIONS: Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d). Placebo and fluoxetine alone were administered double-blind; CBT alone and CBT with fluoxetine were administered unblinded. MAIN OUTCOME MEASURES: Children's Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score. RESULTS: Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P =.001) on the Children's Depression Rating Scale-Revised. Compared with fluoxetine alone (P =.02) and CBT alone (P =.01), treatment of fluoxetine with CBT was superior. Fluoxetine alone is a superior treatment to CBT alone (P =.01). Rates of response for fluoxetine with CBT were 71.0% (95% confidence interval [CI], 62%-80%); fluoxetine alone, 60.6% (95% CI, 51%-70%); CBT alone, 43.2% (95% CI, 34%-52%); and placebo, 34.8% (95% CI, 26%-44%). On the Clinical Global Impressions improvement responder analysis, the 2 fluoxetine-containing conditions were statistically superior to CBT and to placebo. Clinically significant suicidal thinking, which was present in 29% of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction (P =.02). Seven (1.6%) of 439 patients attempted suicide; there were no completed suicides. CONCLUSION: The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.
poster:Larry Hoover
thread:382578
URL: http://www.dr-bob.org/babble/20040825/msgs/382578.html