1 Boring Old Man

Benefits From Antidepressants:
^{Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine
by Robert D. Gibbons, PhD; Kwan Hur, PhD; C. Hendricks Brown, PhD; John M. Davis, MD; and J. John Mann, MD}
Archives of General Psychiatry. Published online March 5, 2012.

…

^{Conclusions: To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.}

^{[only Child and Adolescent data shown]}

A commenter located a reference to it and I finally found it on a Lilly Clinical Trial site, listed under Strattera, not Prozac, because it was primarily an ADHD Study with Prozac as an add-on. Later, someone more adept at searching than I found the actual published version. And so my obsession returned:

With the four child studies and the two Gibbons et al papers in front of me, I found plenty to worry about in the child data. Not only were the two Effexor studies missing – they mattered. They both show no efficacy and they were listed in other meta-analyses as showing a high suicidality rate. And study LYAQ was grossly inappropriate in that only some of the subjects were even depressed [it was an ADHD study].

So the reason my posting mostly stopped in mid-month is that I decided to write a letter to the editor about all the things I had found. That was a leap for me. My scientific writing days ended before I was thirty when I was an NIH fellow. I wrote a lot of things as a psychiatrist, but they were all for local consumption and I never published. So my writing style was as you read it – kind of anecdotal and bloggy. I enlisted the help of all my wives and savvy friends and translated my narrative story-telling letter into a form that stuck strictly to the facts and sounded dry enough to crackle in an envelope. I learned a lot about how to write in that way in the process – a defensive writing aiming to leave no loose ends for a rebuttal. I expunged quotes, formatted and reformatted a couple of tables, and read and re-read the directions. I actually felt pretty good about the product.

The thing I felt good about in the letter was that I thought it was correct. This meta-analysis is deeply methodologically flawed, and in my opinion shouldn’t have been published in the first place. One of the main reasons is Trial LYAQ. There’s just no way to look at it as a study of Major Depressive Disorder:

Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms
^{by Kratochvil CJ, Newcorn JH, Arnold LE, Duesenberg D, Emslie GJ, Quintana H, Sarkis EH, Wagner KD, Gao H, Michelson D, and Biederman J.}
Journal of the American Academy of Child and Adolescent Psychiatry. 2005 44:915-24.

^{OBJECTIVE: Symptoms of depression and anxiety are commonly comorbid with attention-deficit/hyperactivity disorder [ADHD]. The authors assessed the safety and effectiveness of atomoxetine monotherapy compared with combined atomoxetine/fluoxetine therapy in a population of children and adolescents with ADHD and concurrent symptoms of depression or anxiety.
METHOD: Patients were randomized to treatment with fluoxetine [n = 127] or placebo [n = 46] under double-blind conditions for 8 weeks, with concomitant atomoxetine use the last 5 weeks.
RESULTS: At end point, reductions in ADHD, depressive, and anxiety symptoms were marked for both treatment groups [p < .001 for the relevant scale in each symptom cluster]. Some differences between treatment groups for depressive symptoms were significant, but the magnitudes of the differences were small and likely of limited clinical importance. Completion rates for the two groups were similar, as were discontinuation rates for adverse events. The combination group had greater increases in blood pressure and pulse than did the monotherapy group.
CONCLUSIONS: In pediatric patients with ADHD and comorbid symptoms of depression or anxiety, atomoxetine monotherapy appears to be effective for treating ADHD. Anxiety and depressive symptoms also improved, but the absence of a placebo-only arm does not allow us to conclude that these effects are specifically the result of treatment with atomoxetine. Combined atomoxetine/fluoxetine therapy was well tolerated.}

^{"The youth data consisted of 3 outpatient trials and 1 inpatient trial; all subjects had depression (similar to MDD) and were aged 7 to 18 years."}