1 Boring Old Man

"None of the 10 measures relying on patient reported or parent reported outcomes showed significant advantage for an antidepressant, so that claims for effectiveness were based entirely on ratings by doctors."

It’s ragweed season here, so it has been indoors for me. Having just read Paxil Study 329, I read the two Lilly Prozac studies [X065 and HCJE], the Wagner Zoloft study, TADS, then moved on to the meta-analyses [Hammad, Kaizar, Bridge, Jureidini, Gibbons] and the transcripts of the FDA hearings in 2004 that added the Black Box warning. I was beginning to get cross-eyed and had a headache. I wondered what I was looking for this time around. I’m usually reading these articles looking for deceitful presentations or other scientific improprieties [and there are plenty to find]. But  the thing that set off this bout of re-reading was this from the ParentsMedGuide:

Are antidepressant medications effective for the treatment of child/adolescent depression?

^{Yes, antidepressant medications can be effective in relieving the symptoms of depression for some children and adolescents. One antidepressant – fluoxetine, or Prozac – a medicine in the category of selective serotonin reuptake inhibitors, or SSRI’s, has been approved by the FDA for treating depression in children 8 years of age and older. Escitalopram, or Lexapro has also been approved by the FDA for treating adolescents 12 years of age and older. Your physician may prescribe other antidepressant medications as well. You should know that prescribing an antidepressant that has not been approved by the FDA for use with child and adolescent patients [referred to as off-label use or prescribing] is common and consistent with general clinical practice. Atypical antipsychotics, however, are not approved by the FDA for the treatment of depression in children and adolescents and are not considered appropriate for first-line treatment. As generally used, tricyclic antidepressants [e.g. imipramine, amitriptyline] have not been shown to be effective for pediatric depression and they should not be used as the first treatment. About 60 percent of children and adolescents will respond to initial treatment with medication. Of those who don’t, a significant number will respond to another medication and/or to the addition of a form of psychotherapy called cognitive behavioral therapy…}

Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment
^{A Meta-analysis of Randomized Controlled Trials
by Jeffrey A. Bridge, Satish Iyengar, Cheryl B. Salary, Rémy P. Barbe, Boris Birmaher, Harold Alan Pincus, Lulu Ren, David A. Brent}
Journal of the American Medical Association. 2007 297:1683-1696.
[full text on-line]

^{Context: The US Food and Drug Administration [FDA] has issued warnings that use of antidepressant medications poses a small but significantly increased risk of suicidal ideation/suicide attempt for children and adolescents.
Objective: To assess the efficacy and risk of reported suicidal ideation/suicide attempt of antidepressants for treatment of pediatric major depressive disorder [MDD], obsessive-compulsive disorder [OCD], and non-OCD anxiety disorders…
Data Synthesis: Twenty-seven trials of pediatric MDD [n = 15], OCD [n = 6], and non-OCD anxiety disorders [n = 6] were selected, and risk differences for response and for suicidal ideation/suicide attempt estimated by random-effects methods. Pooled risk differences in rates of primary study-defined measures of responder status significantly favored antidepressants for MDD [11.0%; [95% confidence interval {CI}, 7.1% to 14.9%]], OCD [19.8% [95% CI, 13.0% to 26.6%], and non-OCD anxiety disorders [37.1% [22.5% to 51.7%]], corresponding to a number needed to treat [NNT] of 10 [95% CI, 7 to 15], 6 [4 to 8], and 3 [2 to 5], respectively. While there was increased risk difference of suicidal ideation/suicide attempt across all trials and indications for drug vs placebo [0.7%; 95% CI, 0.1% to 1.3%] [number needed to harm, 143 [95% CI, 77 to 1000]], the pooled risk differences within each indication were not statistically significant: 0.9% [95% CI, −0.1% to 1.9%] for MDD, 0.5% [−1.2% to 2.2%] for OCD, and 0.7% [−0.4% to 1.8%] for non-OCD anxiety disorders. There were no completed suicides. Age-stratified analyses showed that for children younger than 12 years with MDD, only fluoxetine showed benefit over placebo. In MDD trials, efficacy was moderated by age, duration of depression, and number of sites in the treatment trial.
Conclusions: Relative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD. Benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across indications, although comparison of benefit to risk varies as a function of indication, age, chronicity, and study conditions.}

^{Similar to the FDA’s analysis, we found an overall increased risk of suicidal ideation/suicide attempt associated with antidepressant treatment. Our pooled estimates of risk differences are smaller than those from the FDA report, because we used random-effects rather than fixed-effects models for combining studies and also because we included 7 additional studies not covered in the FDA report. When we reanalyzed the data using fixed-effects models, our results were more similar to those of Hammad.}

^{Relative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD.}

"None of the 10 measures relying on patient reported or parent reported outcomes showed significant advantage for an antidepressant, so that claims for effectiveness were based entirely on ratings by doctors."