She was one of twenty-five volunteers in a study of larger than therapeutic doses of the investigational antidepressant duloxetine, which Eli Lilly is developing under the trade name Cymbalta. Four days earlier, the apparently non-depressed young woman had been switched from the active drug to the placebo arm of the study. Her death bolsters critics’ claims that antidepressants carry a risk of suicidal tendencies for some, especially younger, people. A federal advisory panel has just recommended that the FDA issue stronger warnings to doctors about the risks of these drugs in children and adolescents. Four other people given duloxetine during earlier trials have also committed suicide, the company revealed. A review panel has told Eli Lilly to stop entering new patients into this study and have all existing subjects receive an evaluation by an independent psychiatrist.

I thought, when I read the news, that the patient’s death was more likely to be an effect of the discontinuation of the drug than of its administration. (The New York Times reporter who wrote this story apparently thinks so too, as I was surprised to find when I scrolled down the article. The reporter is either very psychopharmacologically astute or he has an unattributed advisor in deep background. I was surprised, indeed, that the article includes no comments from psychopharmacologists outside of Eli Lilly spokespeople. Is it possible no one is willing to go on record with comments that will alienate the company?) Antidepressants that are eliminated rapidly from the body after cessation of use, most notably paroxetine, are known to cause a discontinuation syndrome including severe agitation; the investigational drug is another that has rapid elimination and the study design apparently involved high doses of the drug and a so-called ‘crossover design’ in which patients are switched abruptly and unknowingly between the medication and a placebo. You would think Eli Lilly would be aware of the risks of such a practice. My guess is that they were. The profits at stake if Lilly comes up with another blockbuster antidepressant to replace the market share it has lost with the expiration of the patent rights to its cash cow Prozac are worth a few wrongful-death settlements. (My friend Abby points out that human investigation subjects probably indemnify the company against wrongful death during the study anyway; I haven’t looked at a consent form recently and don’t know. This young woman had dropped out of college to participate in the study, for which she was paid $150/day.) Duloxetine is a good candidate for the next big thing; it has a similar mechanism of action to venlafaxine (Effexor) — dual serotonin and norepinephrine reuptake inhibition — which is newer and better than the SSRIs and has supplanted them in terms of prescribing volume and profitability.

As I usually add in covering this ongoing controversy over antidepressant safety, it is not the drug that is dangerous, but the way in which it was administered.