1 Boring Old Man

Dr. Nemeroff’s presentation in London felt like a postcard from the past – a postcard from the time of Paxil Study 329 and TMAP, the time of ghostwriters and chemical imbalance, the period when academic psychiatry and commercial enterprise wore each other like costumes at Mardi Gras bathed in the warm glow of future discovery just up ahead. it was a time when psychiatry had been freed from the shackles of speculation and transported into the light of a new century.

Yesterday, I watched  Dr. Nemeroff’s Grand Rounds presentation at NYU last year again. It was the part at the end about treatment implications that got to me. That story starts with a 2000 industry-funded non-placebo controlled comparison of a forgotten antidepressant and Cognitive Behavior Therapy or the combination. There had been innumerable earlier studies that showed that CBT plus antidepressant beat either one of them alone – so many that we used to joke that every new researcher must have to do a CBT/Antidepressant study as a rite of passage. What was unique was the army of authors and the fact that the New England Journal didn’t have room for all the industry disclosures. The article launched editor Marcia Angell as an anti-COI activist.

I said forgotten antidepressant because by 2003 when Nemeroff’s paper was published, Nefazodone [Serzone®] was being withdrawn from the market in Europe and stopped being sold in the US in 2004 because of hepatotoxicity. So it’s hard for me to see that 2000 study with its cadre of add-on authors as anything but business as usual in an era of junk science, and Dr. Nemeroff’s paper as an afterthought résumé-churner. Speaking of rites of passage, if a post-doc fellow had presented a secondary analysis of an industry funded, non-placebo controlled study to the Institute of Psychiatry at Kings College and made global pronouncements about how to treat chronically depressed patients based on the findings, I think he or she would have been shredded from the floor.

Results of the analyses of variance comparing change in Hamilton Rating Scale for Depression scores as a function of treatment type and early life trauma histories as well as Fig. 1A reflect change relative to the first week of treatment instead of baseline. When change scores relative to baseline are used, the interaction effects between treatment type and childhood trauma histories are not statistically significant. This discrepancy is due to marked changes in depression scores during the first week of treatment.

Note that all analyses comparing the more conservative outcome measure of remission as a function of treatment type and childhood trauma as well as Fig. 1B are correct. Thus, consideration of treatment response relative to baseline does not detect the effect of childhood trauma on final remission, whereas consideration of final response relative to first response does detect the effect.

Dr. Nemeroff is described as charismatic. I don’t know about that, but he’s certainly at home on a podium. All through his career, people have allowed him to get away with things they wouldn’t tolerate in others. They see him as bright, engaging, boyish, maybe an embellisher, but in an innocent sort of way. He’s used to being let off the hook. When he recommended treatments that he had a financial stake in without mentioning it in 2004, he got a hand slap. When he was exposed for writing signing on to a ghost written review of a vagal nerve stimulator with other coinvestors without mentioning his or their stake, he said it was a clerical error and gave up his editorship. When he was busted for unreported income from GSK while PI on a joint GSK NIMH grant and removed as chairman, he said he didn’t understand the rules and got another chairmanship within the year. All of those explanations were untrue, as were his defenses when he was exposed for a ghost-written textbook by POGO a year later.