If you don’t read to the end of this post, check out the punchline at the bottom of the page anyway. Mac users, that’s CMD -⬇︎.
What’s your personal dystopia? Here’s a possibility. Let’s say there’s no social safety net, and you have to choose between a) unemployment and perpetual poverty and b) convincing doctors to prescribe, for non-lethal conditions, drugs that can cause people to become sick with cancer, heart, and lung disease and die, or send them deep into such black despair that they kill themselves. Kids too, for the latter. That’s the job description of a drug rep for Noven Pharmaceuticals, Inc.
Noven makes five drugs. They’re all lousy and whether by chance or design, they all have black box warnings. It must be fun trying to sell drugs with merits like “you probably won’t die if you take this.” Three of their products make up what they call their Women’s Health Division, but if you look at the odds of being hospitalized in grave condition after taking any of them you wonder if the word “Health” shouldn’t be quietly retired. The cancers they cause are in women’s reproductive organs, so scratch “Women” too. They have a new drug for The Division coming out soon. I can’t wait to see which organs women give up in the process of finding out it doesn’t work.
Daytrana. Noven makes a drug for children who don’t pay attention to the right things, or move around too much: Daytrana. Little girls and boys on Daytrana have experienced hellish states of mind on the stuff and the Food and Drug Administration diligently reports it. Daytrana gets its own post, which will be up soon.
Minivell and CombiPatch. Noven makes two hormone products for hot flashes, and I just made myself sick looking at the diseases they cause in exchange for keeping your hair from sticking to your forehead quite so much. Minivelle and CombiPatch double the chance a women over age 65 will develop dementia. Consider that 9% of us have Alzheimer’s by age 65, and like me you’ll think about cutting yourself very short bangs, whether they suit you or not, rather than reach age 65 with an 18% chance of having Alzheimer’s when you get there. Short bangs worked for Carson McCullers (but she only had to look good in black and white). Part of the 9% might be women using hormone drugs, but whatever the composition of the 9%, think of the risks of Minivelle and CombiPatch as raffle in which the prize is dementia. Everyone gets one ticket, except women on MiniV or CombiP, who get two. It’s a better deal than that, though. What fun would dementia be without various cancers, pulmonary embolism and deep vein thrombosis? You’ll get a fistful of tickets. One of them’s bound to win. I forgot to mention that there’s even a chance you’ll get relief from hot flashes. I charted the benefit you can expect from CombiPatch above, and you can read more about the benefit and the harms at FDA.gov.
Brisdelle and Pexeva. Noven set themselves the task of pretending a generic antidepressant is two different drugs for a variety of ailments, none life-threatening, while keeping us from noticing it’s an antidepressant. That’s Brisdelle for hot flashes and Pexeva for depression, anxiety, panic, and obsessive-compulsive disorder, a real Vita-Meta-Vegemin that should find a place in anyone’s medicine cabinet. They’re the subject of this post, with emphasis on Brisdelle.
Noven must have had some funky focus groups to settle on a name like Brisdelle. It sounds like a down-market Barbie®, but it’s re-badged paroxetine, a.k.a. Paxil, or Seroxat, intended only to diminish hot flashes women endure in menopause. Brisdelle is non-hormonal, Noven proclaims on Brisdelle.com. Remember the low-fat diet craze, when products like ketchup and dried fruit proclaimed their fat-freeness and hoped no one minded that they’re 25% to 50% sugar by weight? Paroxetine may not be a hormone, but it is the most difficult to withdraw from of the SSRIs. And oh yeah, it makes people want to kill themselves.
Paroxetine’s original maker, GSK, was fined $2,500,000 for fraud inherent in the white-washed clinical trial that got paroxetine approved for children and adolescents. The data, if reported accurately, would not have led to the drug’s approval. It was ineffective against depression in that age group and induced suicidality at a higher rate than the mis-dosed comparison fall-guy drug and placebo, and worse, at a higher rate than Professor-Doctor Martin Keller and his band of mercenaries reported. GSK was later fined $3,000,000,000 for Medicare and Medicaid fraud. They’d been marketing drugs to prescribers for conditions they hadn’t been tested on. At the time it was the largest fine on record, but Bank of America did us all proud with $16.65 billion last year, also for fraud. I told my 84-year-old dad about that, and he said, “Really? Bank of America? I can’t believe it.” And he doesn’t. Every time I bring it up, he says the same thing. Drugmakers used to command respect, but there’s evidence that’s on the wane.
You might wonder how paroxetine, a drug that makes children and adults want to kill themselves, can also be an antidepressant. Clever you. It can’t. A level-headed group headed by World Health Organization researchers performed a level-headed meta-analysis of 40 published and unpublished paroxetine trials, which included over 6000 participants with major depressive disorder, and found that people randomly assigned to paroxetine groups, compared to people in placebo groups, were more likely to quit the trials early, were two-and-a-half times as likely to feel suicidal, and took the lion’s share of the adverse events. Effectiveness was not impressive. The authors calculated that for every 100 patients prescribed paroxetine, 11 would experience relief that wasn’t due to a placebo effect. That’s no good. That would make their doctors depressed.
So, the active ingredient in Brisdelle, as in Sprout’s recently approved Addyi, is an antidepressant that doesn’t work, which might be why Noven is careful to say it is not indicated for any psychiatric condition. Of course it isn’t. Paroxetine-as-Brisdelle pills supply a 7.5mg dose, which is only 75% of paroxetine-as-Paxil’s 10mg starting dose. (If math’s not your thing, think of a six-pack of 12-ounce cans of Bud Light and a six-pack of 16-ounce cans. How much less drunk would you be if you drank the 12-ounce six-pack instead of the 16-ounce six pack?) Because paroxetine at 7.5mg has not been tested and approved as an antidepressant, Noven is free to say it isn’t one. Yet, as you see below, they relied on the pharmacology of their antidepressant, Pexeva, which is paroxetine marketed as an oral psychiatry product, to lubricate the approval of Brisdelle, which is paroxetine marketed as a non-psychiatry product. Alas, in real life, drug approvals do not have referees with whistles to stop the action when things get out of hand. The “well established safety profile of paroxetine” is deep in the stacks of the University of the Continent of Atlantis, last I heard. But Noven was in dialog with the FDA, so everything was on the up-and-up.
Noven had to battle the FDA for Brisdelle’s approval, just as Sprout did for Addyi’s, and for the same reasons: minimal efficacy and appreciable potential harms. The same “significant number of women with no other options” malarky was used to justify its approval. The untenable other options are gruesome hormone products like Minivelle and CombiPatch that are less ineffective, but so unsafe that the FDA let hardly-works-but-less-unsafe Brisdelle slink in and take her place in the black box seats.
Never mind that among the 1184 women divided evenly between treatment with Brisdelle and placebo for the phase 3 trials, 4 in the treatment group and none on placebo experienced suicidality. One woman attempted suicide and three experienced suicidal ideation. Another woman on Brisdelle just plain died.
I should have mentioned earlier that Brisdelle is not paroxetine per se, and that paroxetine’s full name is paroxetine hydrochloride. Like Pexeva, Brisdelle is paroxetine mesylate, which is close enough for the FDA to use paroxetine hydrochloride and paroxetine mesylate interchangeably. Noven does too. It’s explicit in the “referreed” quote above, which came from a document Noven prepared for the FDA during the Brisdelle [pre]approval process. which should get a few bloggers shouting at their monitors, and all of us united in calling for an overhaul of drug safety evaluation. An overhaul is imperative in light of the FDA’s slack-jawed acceptance of Keller et al.’s patently worthless and arguably murderous paroxetine study, which greased the skids for any number of similar drugs’ approvals, and its pathetic obeisance to a twisted notion of woman’s rights in the flibanserin flameout.
Noven is aware of the discontinuation syndrome faced by Paxil users, yet they disguise it in word play. They say Pexeva’s not addicting. Well, it does not induce cravings, but that’s the only distinction. Withdrawal and the aftermath are hellish for an unknown percent of users. The aftermath can go on for years. “That’s why you should never stop your medication without speaking to your doctor first, even if you start feeling better.” By the time you start feeling better, on the off chance you do, it’s too late.
Would you sell Brisdelle, Pexeva, Daytrana, Minivelle, and Combipatch for a charismatic humanist like Jeffrey Eisenberg? Noven’s hiring. Someone’s got to win that Lexus this year and it might as well be you. Where else could you work and sell five products that all have black-box warnings? That’s right. Brisdelle, Pexeva, Daytrana, Minivelle, and Combipatch, none of which save lives, can cause lives to end. Don’t worry, though. In a paraphrasing of the newly minted but inevitably immortal words of Dr. Keller himself, in his ineffective plea of innocence following the exposure of Study 329, no one’s going to pin it on you.
Maybe not, but there is a social safety net. There’s no excuse for helping Jeffrey Eisenberg hurt people.
If you were pondering the moral dilemma, you’re off the hook. Looks like another one’s bitten the dust, a hazard of working with mortar and pestle.