{"id":19389,"date":"2012-02-09T16:36:00","date_gmt":"2012-02-09T21:36:00","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=19389"},"modified":"2012-02-09T21:29:50","modified_gmt":"2012-02-10T02:29:50","slug":"a-book-review","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2012\/02\/09\/a-book-review\/","title":{"rendered":"a book review…"},"content":{"rendered":"
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Editorial Coment<\/font><\/strong><\/td>\n<\/tr>\n
I’m showing these studies to look at the antidepressant-suicidality-in-adolescents<\/em> question, but before getting to that, there’s something else. I was taught to be vigilant for graphmanship<\/em> [using tricks to make graphs look better], so I usually replot data full-scale as I’ve done here. My comment is "no great shakes<\/em><\/font><\/strong>" in any of these studies. The major significant is time<\/em>, not treatment effect [if penicillin worked like this, it would’ve probably never been discovered]. So treatment effects here may be significant<\/em>, but they’re hardly exciting.<\/sup><\/td>\n<\/tr>\n<\/table>\n

The question of the use of antidepressants in depressed children and adolescents lives on [and on]. Previously, I’ve reported the industry funded studies shown here with the drug\/date [see tuning the quartet…<\/font><\/a><\/strong><\/u>]:<\/p>\n


[replotted to full scale]<\/sup><\/p>\n

All report positive results. There was another NIMH study around that time that should be added to the mix:<\/div>\n
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Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents With Depression<\/font><\/strong><\/u><\/a>
Treatment for Adolescents With Depression Study (TADS) Randomized Controlled Trial<\/sup>
Journal of the American Medical Association<\/font><\/strong>. 2004 292:807-820.
[full text on-line<\/font><\/strong><\/u><\/a>]<\/div>\n

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Objective<\/font><\/strong><\/u>: 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<\/font><\/strong><\/u>: 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<\/font><\/strong><\/u>: Children’s Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score.
Results<\/font><\/strong><\/u>: 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<\/font><\/strong><\/u>: The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.<\/sup><\/div>\n

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[replotted to full scale]<\/sup><\/div>\n

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[reformatted and abbreviated]<\/sup><\/div>\n<\/blockquote>\n
There was a brisk response to this JAMA TADS article [letters here<\/font><\/strong><\/a><\/u>]. Using epidemiological calculations, Carroll saw the adverse and therapeutic effects balancing each other in terms of suicidality [author March disagreeing]. Others split evenly in their responses. Recall that it was towards the end of 2004 that the FDA required that the antidepressant manufacturers add a black box warning about increased child and adolescent suicidality to their literature and package inserts… <\/div>\n

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…and we’ve spoken of little else since that time, even though these drugs were never approved for pediatric use by the FDA. Their Warning was obviously heeded:<\/p>\n

\"from<\/a><\/p>\n

In the last post, I discussed the recurrent claims that adding this warning increased suicides in adolescents or deprived kids of their needed treatment with antidepressants [hope springs…<\/font><\/a><\/strong><\/u>]. Then, as if on cue, the study below appeared yesterday on the Internet, along with a quick retort on Dr. David Healy’s blog. Healy was active in the early identification of the problem of suicidality with antidepressants and he leaped on this study [Coincidence a fine thing<\/font><\/strong><\/u><\/a>]: <\/div>\n
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Suicidal Thoughts and Behavior With Antidepressant Treatment<\/font><\/strong><\/u><\/a>
Reanalysis of the Randomized Placebo-Controlled Studies of Fluoxetine and Venlafaxine<\/sup><\/font><\/strong>
by Robert D. Gibbons, PhD; C. Hendricks Brown, PhD; Kwan Hur, PhD; John M. Davis, MD; and J. John Mann, MD<\/sup>
Archives of General Psychiatry<\/font><\/strong>. Published online February 6, 2012.<\/div>\n
[full text on-line<\/font><\/strong><\/u><\/a>]<\/div>\n

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Context<\/font><\/strong><\/u>: The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults.
Objective<\/font><\/strong><\/u>: To determine the short-term safety of antidepressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms.
Data Sources<\/font><\/strong><\/u>: All intent-to-treat person-level longitudinal data of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride.
Study Selection<\/font><\/strong><\/u>: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine.
Data Extraction<\/font><\/strong><\/u>: The suicide items from the Children’s Depression Rating Scale–Revised and the Hamilton Depression Rating Scale as well as adverse event reports of suicide attempts and suicide during active treatment were analyzed in 9185 patients (fluoxetine: 2635 adults, 960 geriatric patients, 708 youths; venlafaxine: 2421 adults with immediate-release venlafaxine and 2461 adults with extended-release venlafaxine) for a total of 53 260 person-week observations.
Data Synthesis<\/font><\/strong><\/u>: Suicidal thoughts and behavior decreased over time for adult and geriatric patients randomized to fluoxetine or venlafaxine compared with placebo, but no differences were found for youths. In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior.
Conclusions<\/font><\/strong><\/u>: Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal personlevel data from a large set of published and unpublished studies.<\/sup><\/div>\n<\/blockquote>\n
Dr. Gibbons is the Director of the Center for Health Statistics<\/font><\/strong><\/u><\/a> at the University of Chicago and has had a long-held interest in this topic. He has consistently challenged the anti-depressant\/suicidality connection: <\/div>\n