The Dec. 9, 2013, issue of The New Yorker published a detailed but rather misguided article by Ian Parker, "The Big Sleep," about the complicated tangle of profit, science, and psychology in the search for better drugs to aid sleep. Recently there have been troubling stories about people suffering strange side effects from zolpidem (marketed as Ambien), such as driving, eating, and having sex while completely asleep. For many years zolpidem/Ambien has been the best selling prescription sleep aid in the US, but the rising concerns about the bizarre side effects have motivated other drug companies to try inventing an alternative.
Parker's article focuses on several employees at the pharmaceutical giant Merck who developed a totally new kind of sleep aid, suvorexant, and were preparing to defend its safety at a government approval meeting with the Food and Drug Administration in May of 2013. Parker casts this encounter as a morality tale pitting the good, reasonable Merck scientists against the bad, slow-witted government officials. The most dastardly villain in the story is the lead investigator for the FDA, Ronald Farkas, a neuroscientist who reviewed Merck's data on the clinical effects of suvorexant. This is how Parker describes Farkas' presentation at the meeting:
In a relentless PowerPoint sequence, Farkas made suvorexant sound disquieting, almost gothic. He noted suicidal thoughts among trial participants, and the risk of next-day sleepiness. He quoted from Merck's patient notes: "Shortly after sleep onset, the patient had a dream that something dark approached her. The patient woke up several times and felt unable to move her arms and legs and unable to speak. Several hours later, she found herself standing at the window without knowing how she got there." A woman of sixty-eight lay down to sleep "and had a feeling as if shocked, then felt paralyzed and heard vivid sounds coming up the stairs, with a sense of violent intent." A middle-aged man had a "feeling of shadow falling over his body, hunted by enemies, hearing extremely loud screams."
The rest of the article ignores these concerns and focuses instead on explaining why zolpidem is more dangerous than generally assumed, and why suvorexant is a more efficient medication for inducing sleep. Parker never addresses the specific questions raised in the FDA presentation about the occurrence of highly disturbing dream and sleep phenomena in people taking suvorexant. As one of the Merck scientists rightly pointed out, a few "adverse effects" should not be surprising in large clinical trial with thousands of participants. But did Merck do any further study of these dream-related side effects to see how widespread they were, what different forms they took, and what impact they had on people's lives? Apparently not. The fact that Zarkas raised these concerns is treated not as evidence against suvorexant, but rather as evidence against Zarkas and the seriousness of his critique. So what if suvorexant disrupts dreaming? Why should real scientists pay attention to a few bad dreams?
Parker writes persuasively about the advantages of suvorexant over zolpidem in terms of their different effects on the brain. Zolpidem works like previous generations of sleep aids (barbituates, Valium, Halcion) in triggering the neurotransmitter GABA, which inhibits activity all over the brain--it's a general knock-out drug, hence the problems with amnesia, confusion, and disinhibition. Suvorexant, however, focuses specifically on orexin, a recently discovered neurotransmitter that plays a key role in maintaining wakefulness. By lowering the activities of orexin, suvorexant enables people to fall asleep and stay asleep with less grogginess upon awakening.
However, Parker and the Merck scientists seem oblivious to the concerns about the variable psychological effects of this new medication. Merck wanted the FDA to focus on two questions only: One, does suvorexant induce sleep? Two, can people who take suvorexant perform adequately on cognitive tests after waking? The problem, apparently, is that the FDA wanted to ask questions beyond just these two.
I wish the FDA would ask even more questions. I wish Merck and other drug companies were compelled to give far more detailed answers about the long-term effects of using these powerful brain-changing sleep medications. How exactly are people's dreaming patterns affected? What about their emotional balance over time? Their relational abilities? Their interactions with their families and friends? Their creative energy, curiosity, and openness to new experiences? Their engagement as citizens? If millions of people are going to be spending billions of dollars to use this drug for years on end, shouldn't we have some idea of the answer to these questions? Is it really beyond the pale of "true science" to even ask such questions?
If nothing else, consider this: As Parker notes, the neurotransmitter orexin was discovered just a few years ago, in 1998. Does Merck or anyone else know what happens to the human brain over time if orexin levels are continually raised or lowered by artificial chemical means? The answer is clearly no. There has not been enough time to conduct that kind of longitudinal research. Yet Parker's article encourages us to feel frustration with the government and sympathy with the big pharmaceutical company because the FDA is not racing to approve this new orexin-manipulating drug.
Ronald Farkas is my new hero.
Actually, Parker does come back to the topic of dreams at the very end of the article, when he is describing Merck's efforts to persuade the FDA that suvorexant will not produce narcolepsy in people by depleting them of orexin. In parentheses, Parker notes:
Emmanuel Mignot, [a sleep] researcher at Stanford, recently told me that suvorexant seems to produce a rather normal experience of sleep, except that patients are hurried into the REM phase, which is also the experience, in a more extreme way, of narcoleptics. Suvorexant might not be the best drug for people prone to nightmares, he said.
Mignot is neither a Merck employee nor a government hack, so his third-party expert view would seem to be highly credible. And guess what? He immediately sees a potential downside to suvorexant in relation to its effects on dreaming. Mignot's comment is exactly in line with the concerns raised by Farkas in his "unfriendly" PowerPoint presentation. The fact that this crucial admission of potential harm is relegated to a late parenthetical aside makes it painfully clear that dream research is not treated as a legitimate part of the scientific discussion, at least in big drug company presentations and in the pages of The New Yorker.