{"id":32078,"date":"2013-01-14T23:00:41","date_gmt":"2013-01-15T04:00:41","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=32078"},"modified":"2013-01-15T04:48:32","modified_gmt":"2013-01-15T09:48:32","slug":"ask-alice","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/01\/14\/ask-alice\/","title":{"rendered":"ask Alice…"},"content":{"rendered":"\n

The Eli Lilly documents I mentioned in the last post [foul…<\/a>] have quite a history indeed. Little wonder I said, "I got really lost following the timeline and their exact path from sealed documents into the public domain, and promise to try to get that in order soon.<\/em>" Dr. Peter Breggin had the first shot at them as an expert witness "Dr. Breggin originally found, examined and evaluated each of these documents in the early 1990s when he was the plaintiffs’ medical and scientific expert for the combined Multi-District Litigation [MDL] concerning Prozac.<\/em>" He’s written up their subsequent history which I couldn’t possibly summarize [An Examination of Eli Lilly and Company’s Contentions that the BMJ Prozac Documents were Never Missing and Have No Significance<\/span><\/a>], but it sounds like a plot in a John le Carr\u00e9 novel and is worth reading over. As he tells it, as the dicuments appeared in recurrent suits against Lilly. The suits would be settled privately and the documents would be sealed and then disappear. Finally they were leaked to the British Medical Journal who forwarded them to the FDA and a member of Congress. Lilly denies involvement in their disappearance.<\/p>\n

As for the characters mentioned in the emails, they were high-ups in Lilly at the time, in Europe and in the US. I’ve added links to the info I could find [Further links and information on David Healy’s Let them Eat Prozac<\/font><\/strong> site<\/a> and on AHRP<\/a>]:<\/p>\n\n\n
\n
This is message #1 from: BOUCHY CLAUDE<\/a><\/strong><\/sup><\/div>\n
November 13, 1990 10:49<\/strong><\/sup><\/div>\n
To: THOMPSON LEIGH<\/a>, WEINSTEIN ALLAN J<\/a>, ZERBE ROBERT L<\/a><\/strong><\/sup><\/div>\n
CC: MAYR GERHARD<\/a>, TAUREL SYDNEY<\/a>, WEBER HANS J<\/a><\/strong><\/sup><\/div>\n<\/td>\n<\/tr>\n<\/table>\n

Interlude: I find myself with that d\u00e9jà vu feeling again. I’m a late comer to all of this pharmaceutical business, having spent my life in another corner of the psychiatric world, and just when I think I’m finally getting caught up, I run into some new thing like "329" or "TMAP" or "STAR*D" and I start nosing around and there’s some huge saga laying in wait behind a tree. So after I clicked on Pharmagossip’s links to those Lilly emails this weekend, I found myself today falling down another rabbit hole into an alternative universe that a lot of you know all about, but I didn’t even it know was there. <\/em><\/p>\n

Here’s just a piece of the story. It’s from a legal brief kindly forwarded by Leehmon McHenry from the Baum Hedlund law firm. It tells the story of Prozac being turned down by the BGA [Germany’s FDA] and why:<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n <\/tr>\n<\/table>\n

Prozac was turned down in Germany in 1985 because of the akathisia and suicidality [43]. That report that says “The benefits vs. risks consideration for [Prozac] currently does not fall clearly in favor of the benefits<\/em>” came from, Professor Herrmann, a consultant hired by Eli Lilly [44] – their own consultant! When the FDA asked Lilly why they were being turned down in Germany, Lilly lied outright, saying that the BGA didn’t say. When the BGA finally did approve Prozac, they required a warning [49][50]. There’s an online petition<\/a> from a group called SSRI-Crusaders that has a very good narrative, including where those emails in the last post fit.<\/p>\n

So here I am down in another obviously well traveled rabbit hole. The corporate misbehavior is everywhere – altered data, missing emails, lying to the FDA, legal maneuvering. The most amazing part to me is that we can read that this<\/a> started in 1978: <\/em><\/div>\n
\n
Eli Lilly has known Prozac (fluoxetine) causes akathisia, defined as an extreme subjective feeling of inner restlessness. This condition has long been known to be caused by antipsychotic drugs and recognized as leading to suicidal and homicidal-suicidal feelings. Lilly’s own internal documents show the condition was identified in association with Prozac as early as 1978.  August 2, 1978, when only three trials were underway, minutes of a meeting of the Fluoxetine (Prozac) Project Team read: "There have been a fairly large number of reports of adverse reactions… Another depressed patient developed psychosis… Akathisia and restlessness were reported in some patients." A similar meeting held 10 days earlier stated, "some patients have converted from severe depression to agitation within a few days; in one case the agitation was marked and the patient had to be taken off [the] drug." The minutes further state, "in future studies the use of benzodiazepines to control the agitation will be permitted. From that point on, Lilly’s trial subjects were put on tranquillizers to get them over the akathisia experienced by some in the early days on the drug. Those who developed akathisia or who had any suicidal tendencies were excluded from the trial data on the basis that they would otherwise obscure the results of the drug’s success in treating depression.<\/strong><\/sup><\/div>\n<\/blockquote>\n
<\/strong>and yet here in 2013, we still spend no small amount of time dealing with studies by Martin Keller [2001] or Robert Gibbons [2012] who try to deny what was known all those years ago. And Prozac is the index drug, the one that started this whole avalanche of the me-too drugs that poured from the pipeline aided by the widespread pharmaceutical-academic alliances that have made swiss cheese out of psychiatry for over three decades. Lewis Carroll and Alice didn’t have anything on us…<\/em><\/div>\n","protected":false},"excerpt":{"rendered":"

The Eli Lilly documents I mentioned in the last post [foul…] have quite a history indeed. Little wonder I said, "I got really lost following the timeline and their exact path from sealed documents into the public domain, and promise to try to get that in order soon." Dr. Peter Breggin had the first shot […]<\/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":[2],"tags":[],"class_list":["post-32078","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/32078","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=32078"}],"version-history":[{"count":30,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/32078\/revisions"}],"predecessor-version":[{"id":32109,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/32078\/revisions\/32109"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=32078"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=32078"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=32078"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

ADDITIONAL PROPOSED FINDINGS OF FACTS<\/strong><\/sup><\/td>\n<\/tr>\n
39.<\/strong><\/sup><\/td>\n German regulators expressed concerns about Prozac and an increased risk of suicidality in the early 1980’s, before Prozac was approved for marketing.<\/strong><\/sup><\/td>\n<\/tr>\n
40.<\/strong><\/sup><\/td>\n According to a May 25, 1984 internal memorandum from Eli Lilly and Company (“Lilly”) regarding Lilly’s efforts to obtain registration of Prozac in Germany: “During the treatment with the preparation [fluoxetine\/Prozac] 16 suicide attempts were made, 2 of these with success. As patients with a risk of suicide were excluded from the studies, it is probable that this high proportion can be attributed to an action of the preparation in the sence (sic) of an deterioration of the clinical condition, which reached its lowest point.”<\/strong><\/sup><\/td>\n<\/tr>\n
41.<\/strong><\/sup><\/td>\n According to a June 26, 1984 Lilly memorandum, item # 10: “The BGA [German equivalent of FDA] suspects fluoxetine [Prozac] to be a stimulating\/activating drug (side-effect profile, suicides, suicide attempts).” Item # 14 states: “This is a very serious issue in the opinion of the BGA. It might well be that we will have to recommend concomitant tranquilizer intake for the first 2 or 3 weeks in the package literature.”<\/strong><\/sup><\/td>\n<\/tr>\n
42.<\/strong><\/sup><\/td>\n A January 29, 1985 memo states: “Two major concerns [regarding the Prozac application] seem to be the reason that the registration [in Germany] was not accepted,” “efficacy questioned” and “suicidal risk.”<\/strong><\/sup><\/td>\n<\/tr>\n
43.<\/strong><\/sup><\/td>\n On February 26, 1985, the German Regulatory Authority told Lilly “we intend to refuse the registration of [Prozac] for the following reasons.” 2.1 states: “The use of [Prozac] seems objectionable, as the increase in agitating effect occurs earlier than the mood elevating effect and therefore an increased risk of suicide exists.”<\/strong><\/sup><\/td>\n<\/tr>\n
44.<\/strong><\/sup><\/td>\n A March 29, 1985 Preliminary Report of Benefit\/Risk Considerations concerning Prozac written by Professor Herrmann, a professor in Germany who was hired by Eli Lilly to help the company obtain approval of Prozac in Germany, stated:“The BGA are making the objection that initially activation and agitation occur before the drug works antidepressively, and that a higher rate of suicides might result from this.” The report further states: “Overall it holds true that the higher incidence rate, for which an explanation must be found, remains in the initial phase as well as in view of the entire duration of treatment, in looking at all patients as well as patients of controlled studies. If an explanation cannot be found for this, this fact will remain a significant obstacle to approval in the Federal Republic of Germany.”. “The fact that suicide attempts are more frequent with Prozac than with imipramine [an older, comparison antidepressant] remains to be explained.” “The benefits vs. risks consideration for [Prozac] currently does not fall clearly in favor of the benefits. Therefore it is of greatest importance that it be determined whether there is a particular subgroup of patients who respond better to Prozac than to imipramine, so that the higher incidence of suicide attempts may be tolerable.”<\/strong><\/sup><\/td>\n<\/tr>\n
45.<\/strong><\/sup><\/td>\nAccording to an April 1, 1986 memorandum of a meeting with Professor Herrmann: “Still not resolved is the fact that suicide attempts have been observed more frequently on fluoxetine as compared to imipramine…. According to the today’s knowledge [fluoxetine’s ‘favourable’ side effect spectrum] is negatively affected by the increased suicidal risk.”<\/strong><\/sup><\/td>\n<\/tr>\n
46.<\/strong><\/sup><\/td>\n According to a December 8, 1987 FDA memo, the FDA had asked Lilly for an explanation of Germany’s concerns about Prozac. The memo, written by Dr. Richard Kapit states: “On December 4, 1987, [Lilly sent a letter to the FDA]…. regarding comments made by the German regulatory authority (the BGA) on the safety of Prozac…. The letter asserted that the German authorities never defined or documented the phrase … ‘unacceptable damaging effects’… The company asserts that all information made available to the BGA has been made available to the FDA, and to their knowledge, the FDA has used more sophisticated analyses in reviewing the data…. Conclusion: The BGA comments do not appear to reflect clinical events, since no such events have been reported to the FDA, and according to the company, we have received all information submitted to the BGA. Recommendation: The comments by the BGA should not affect FDA’s conclusion that [Prozac] NDA 18-936 is approvable.”<\/strong><\/sup><\/td>\n<\/tr>\n
47.<\/strong><\/sup><\/td>\n However, the February 26, 1985 memo described above did explain Germany’s concerns that “the increase in agitating [over-stimulating] effect occurs earlier than the mood elevating effect and therefore an increased risk of suicide exists.”<\/strong><\/sup><\/td>\n<\/tr>\n
48.<\/strong><\/sup><\/td>\n In April 1988, Lilly received “a bad surprise … an official letter from the BGA officially rejecting our application for registration!”<\/strong><\/sup><\/td>\n<\/tr>\n
49.<\/strong><\/sup><\/td>\n Lilly continued to pursue its application for approval of Prozac in Germany and in an August 30, 1989 memo, Lilly received feedback from the “Commission A” (an expert working\/consultant group to BGA), stating that a “counterindication [for Prozac] because of acute suicidality should become a warning whereby the physicians should be advised that in the absence of sedation, the risk of higher suicidality should be taken into account.”<\/strong><\/sup><\/td>\n<\/tr>\n
50.<\/strong><\/sup><\/td>\n Lilly eventually gained BGA approval in 1989, but agreed to include in the German prescribing guidelines for Prozac a warning that the use of sedatives may be necessary to counteract Prozac’s activating side effects.<\/strong><\/sup><\/td>\n<\/tr>\n