There is much buzz about a just-released report in the clinical journal Neurorehabilitation, which reports a case study of three patients, reportedly diagnosed with long-term persistent vegetative state, who were returned to full consciousness for a number of hours with doses of zolpidem, the medication in the sleeping pill “Ambien”. Clinicians and ethicists are warily interested; the “pro-life” blogosphere, of course, is uncritically beside itself over the news:

End the Madness: PVS is reversible or misdiagnosed [Pro-Life Blogs]

PVS is reversible and often misdiagnosed [HyScience]

Important News: Drug ‘Reverses’ Vegetative State  [BlogsforTerri]

Rise and Talk [Premature Terminal Delivery]

Holy Cow! Patients in PVS Awakened by Sleeping Pill [Wesley J. Smith]

etc.

The Terri Schindler Schiavo Foundation has already demanded a moratorium on terminations of treatment for all patients in PVS on the strength of this report, as has their easily-misled former spokesperson, Pamela Hennessy.

That’s a lot of mileage to get out of preliminary reports of a case-study article (i.e., not an experimental report, just a clinical anecdote) involving a total of three patients. I suspect almost none of those jumping on this bandwagon have even read the report, appearing as it does in a limited-circulation clinical journal that is not available online. Glen McGee has a more measured reaction at bioethics.net, pointing out the slimness of the evidence as well as the fact that the one of the two authors is not a neurologist, and both have a habit of finding weird uses for Ambien (which is noted for its unusual side effects, including extended periods of complex action without conscious recall). As McGee points out:

The hypothesis that this set of side effects, which according to Aventis spokesmen occur in less than 1 in 1,000 cases – might be really really common in treating people who are basically dead strains credibility.

I would go further to note that the evidence may not even be as “strong” as an anecdotal report with n=3 suggests. The newspaper reports on the patients in the trial describe one’s reaction to the drug as being a transformation from “constantly uttering random screams” to more normal interactions – but if this is the case, he almost certainly wasn’t in a persistent vegetative state. Reflexive movements and even noises are found in PVS, but “constant random screams”, I think, are not. That raises a significant question whether any of these patients were truly in PVS. Yet another issue is the report that this remarkable “awakening” phenomenon has supposedly been observed in these patients on an almost daily basis for three years. They’re telling us that they can cure PVS on demand, and have been doing so for several years running – and they just now got around to mentioning it to anybody!? It’s hard to take this seriously.

One may also tentatively raise the question of how this is supposed to be happening. Without real clinical data, we are in no position to evaluate these reports, but yet another reason to look askance is the publicly-described patient histories: all three were young men who suffered head injury in car accidents. It’s hard to understand how a neuropharmaceutical could undo the persistent effects of physical injury, especially on a reversible basis; if the injury is severe enough to cause PVS, a drug should not undo that damage, let alone in a 20-minute period, for just 4 hours. (Compare Oliver Sacks’s patients, “awakened” by l-Dopa; they lacked a natural neurotransmitter, and awakened when he dosed them with a trasmitter mimetic, then lapsed back when it wore off. But these new patients reportedly suffered organic damage from physical injury, not a neurochemical pathway disturbance - how does a neuro drug overcome that?) As I said, speculating without clinical evidence gets us into Bill Frist territory – something to be avoided – but it’s still hard to imagine a mechanism for these reports. 

This news, if it pans out and stands up to scrutiny and eventual clinical testing, will be earthshaking. However, there’s more than enough good reason to be skeptical until more-solid evidence comes in. The gullible right wing has already declared that the entire concept of PVS is vacated by these provocative case reports; a more cautious approach may be in order for the reality-based community.

As a final speculative note, however, I offer my expectation: the reports will turn out to be false. I predict, with the expectation of being vindicated, that: (1) no patients “awakened” by zolpidem were actually in clinically-confirmable PVS; (2) no patients in true PVS will be “awakened” by zolpidem, temporarily or permanently; (3) the reports of repeated daily “awakenings” will turn out to be grossly exaggerated; (4) the degree of normal function regained by these patients after “treatment” will be grossly exaggerated. I further predict, with some risk of being wrong, that: (5) at least one, maybe all, of these patients will turn out to display variable degrees of consciousness as part of their longstanding clinical condition without the use of zolpidem; (6) there is actually no observable difference in patient demeanor before and after zolpidem administration, and the case reports are merely selected instances of unremarkable incidents, a la the Schiavo “balloon video”.

That’s what I expect. If the case report stands up, I’ll be wrong, and some major changes will have to occur in our thinking about non-responsive patients. Let’s check back after the dust settles.

PS: One final prediction, in which I have 100% confidence: if these case reports are disproven, they will not be repudiated by “pro-life” bloggers or activists, and we will continue to hear about these “miracle cures” and how PVS is a fictitious and deadly conspiracy diagnosis, for years to come.