{"id":63224,"date":"2016-01-29T17:56:26","date_gmt":"2016-01-29T22:56:26","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=63224"},"modified":"2016-01-29T18:10:18","modified_gmt":"2016-01-29T23:10:18","slug":"in-the-old-days","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/01\/29\/in-the-old-days\/","title":{"rendered":"in the old days…"},"content":{"rendered":"
I took a several week unpaid leave of absence from blogging and email commerce to do a number intense project. I found that I just couldn’t do it if I thought about anything else. I finished the part that had to be done yesterday, and look forward to returning to my normal mental life. Looking over all the accumulated emails, I ran across one from a medical school friend who sent me a blurb from his literature [he’s an Emergency Medicine physician]. It was in Emergency Medicine Today<\/a>:<\/div>\n
hat tip to Ferrell…<\/font><\/strong>  <\/sup><\/div>\n
\n
Antidepressants Appear To Be Much More Dangerous For Kids, Teens Than Reported In Medical Journals, Review Finds.<\/font><\/strong><\/div>\n

HealthDay<\/a> reports, “Antidepressants appear to be much more dangerous for children and teens than reported in medical journals, because initial published results from clinical trials did not accurately note instances of suicide and aggression,” a review<\/a> published Jan. 27 in the BMJ suggests. Researchers arrived at that conclusion after analyzing data from “68 clinical study reports from 70 drug trials that involved more than 18,500 patients.” The clinical studies “involved five specific antidepressants: duloxetine [Cymbalta], fluoxetine [Prozac], paroxetine [Paxil], sertraline [Zoloft] and venlafaxine [Effexor].” <\/p>\n

According to Medical Daily<\/a>, “the limitations in both design and reporting of clinical trials may have led to ‘serious under-estimation of the harms.’” The study authors concluded, “The true risk for serious harms is still uncertain.” The Telegraph<\/a> [UK] also covers the story.<\/div>\n<\/blockquote>\n
At first I thought it was an acknowledgement of our recent article [Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence<\/a>], but it was better than that. It was an article from the Nordic Cochrane Center<\/font><\/em> about the potential adverse effects in adolescents from SSRIs – another log on the fire: <\/div>\n
\n
Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports<\/a><\/div>\n
by Tarang Sharma, Louise Schow Guski, Nanna Freund, and Peter C. Gøtzsche<\/div>\n
British Medical Journal.<\/font><\/strong> 2016 352:i65<\/div>\n
[full text on-line<\/a>]<\/div>\n

<\/p>\n

Objective<\/u>:<\/font><\/strong> To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.<\/div>\n
Design<\/u>:<\/font><\/strong> Systematic review and meta-analysis.<\/div>\n
Main outcome measures: Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.<\/div>\n
Data sources<\/u>:<\/font><\/strong> Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website.<\/div>\n
Eligibility criteria for study selection<\/u>:<\/font><\/strong> Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.<\/div>\n
Data extraction and analysis<\/u>:<\/font><\/strong> Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method [fixed effect model].<\/div>\n
Results<\/u>:<\/font><\/strong> We included 70 trials [64 381 pages of clinical study reports] with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality [all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06], suicidality [1.21, 0.84 to 1.74], and akathisia [2.04, 0.93 to 4.48] were not significant, whereas patients taking antidepressants displayed more aggressive behaviour [1.93, 1.26 to 2.95]. For adults, the odds ratios were 0.81 [0.51 to 1.28] for suicidality, 1.09 [0.55 to 2.14] for aggression, and 2.00 [0.79 to 5.04] for akathisia. The corresponding values for children and adolescents were 2.39 [1.31 to 4.33], 2.79 [1.62 to 4.81], and 2.15 [0.48 to 9.65]. In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.<\/div>\n
Conclusions<\/u>:<\/font><\/strong> Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.<\/div>\n<\/blockquote>\n
Since the article is online, I’ll skip the details and say why I liked it, over and above it being another loud message about the potential harms of SSRIs<\/font><\/em> in adolescents as well as the pressing need for Data Transparency in Clinical Trials<\/font><\/em>:<\/div>\n
    <\/p>\n
  • \n
    The reference came from a primary care newsletter<\/font><\/em>. Non-psychiatrist physicians prescribe the majority of the SSRIs, and that’s where this information about harms belongs. Hopefully the news is finally spreading.<\/div>\n<\/li>\n
  • \n
    The heavy lifting in this article was done by students<\/font><\/em> working with Dr. Gøtzsche at the Nordic Cochrane Center<\/font><\/em>. We desperately need for this kind of critical evaluation of Clinical Trials to be coming from the world of young researchers and physicians rather than just from us old guys.<\/div>\n<\/li>\n
  • \n
    They did this meta-analysis using a large number of Complete Study Report<\/font>s[ CSR<\/font>s] they got from the European Medicines Agency <\/font>[EMA<\/font>]. Again, great news that they could get them. And there was more, they got to see the wide variability in what was in those reports and how variable they were with raw data – clarifying that in lobbying for Data Transparency<\/font>, we need to specify that they have actual data<\/font>.<\/div>\n<\/li>\n
  • \n
    They emphasize the point that that the CSRs are not enough to evaluate harms. We absolutely need to have access to the Case Report Forms <\/font>[CRF<\/font>s] where the data was originally transcribed. We couldn’t have done our Paxil Study 329 article without them.<\/div>\n<\/li>\n
  • \n
    Their findings mirrored ours from Paxil Study 329, but they had information from many more studies than just our one source. It is a more general commentary.<\/div>\n<\/li>\n
  • \n
    It’s always great to hear from an old friend from the time when the world was young [among many other things, ironically, we were lab partners in pharmacology<\/font><\/em> lab a little over 50 years ago]…<\/div>\n<\/li>\n

    <\/span><\/ul>\n

    But happy talk aside, we shouldn’t even have to be fighting for honesty and transparency is the scientific literature. That ought to be a given. As a young guy, I noticed that the elders always talked about the good old days when things were better and I resolved not to do that when I got old. In the main, I have been able to hold to that resolution. But with this issue of the Clinical Trial articles in the medical literature, I can’t stick to my guns. I can’t remember ever having to keep one eye always cocked, looking for signs that I’m being taken for a ride by a distorted, commercially biased production. It really was better in the old days…<\/div>\n","protected":false},"excerpt":{"rendered":"

    I took a several week unpaid leave of absence from blogging and email commerce to do a number intense project. I found that I just couldn’t do it if I thought about anything else. I finished the part that had to be done yesterday, and look forward to returning to my normal mental life. Looking […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-63224","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/63224","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=63224"}],"version-history":[{"count":24,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/63224\/revisions"}],"predecessor-version":[{"id":63248,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/63224\/revisions\/63248"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=63224"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=63224"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=63224"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}