Can Ambien Wake Up PVS Patients?

The Guardian gives credence to a case report concerning three patients purportedly diagnosed in PVS for more than three years who were "aroused transiently every morning after zolpidem," a sleeping pill. That would be Ambien.

The report, by Clauss and Nel, of Royal Surrey County Hospital and of Family Practice of Pollack Park South Africa, was published in this month's issue of Neurorehabilitation.

There are 26 million annual prescriptions for Ambien, most of which are probably not to patients in a persistent vegetative state.

Recall that Ambien is oft reported to cause odd behavior like sleepcooking, and, as summarized on this page of the ever-helpful Yourlawyer.com, sleepdriving. 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. But what a cool idea for a study. And imagine the informed consent process: give the med, wait until they wake up and (as the study reports) throw a baseball, then consent them to another day's dose.

At best this is the weirdest anecdotal report in the history of neurology - even for a journal that publishes case studies, and one wonders why on earth a larger group of subjects would not be studied before moving to this level of publication (the plural of anecdote is data?) about the most controversial area of end of life care on Earth.

But really the question is what this little report will do to the wide world of Schiavo.

Paul Root Wolpe comments on the most likely response from the right wing: "You see? They really are alive in there, their personalities are just trapped, and if we had given this to Terri she would be talking with us today. Killing them is murder."

So it really matters what is up with this study. Who are the authors? Clauss, a neuro has published a number of case reports about the effect of Ambien on various conditions, e.g., this letter in New England Journal in 2004 on its effect on Spinocerebellar Ataxia. He and Nel co-authored "Effects of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans"" last year in a low-impact German journal. In both 2000 and separately in 2001 they claimed that Ambien aroused patients from a semi-comatose state, in a letter to the editor and in a case report, in the South African Journal of Medicine. Claus is a "Consultant Nuclear Medicine Physician" at Surrey, not exactly working in neuropharmacology, but has been active in publishing lots of these little case studies about a wide variety of uses of Ambien. Yet the Guardian writes:

Ralf Clauss of the nuclear medicine department of the Royal Surrey County hospital, one of the authors, said that clinical trials were now needed. He said the drug could have uses in all kinds of brain damage, including Parkinson's disease and Alzheimer's.

So is this the biggest story in the long history of debate about persistent vegetative state, plural anecdotal evidence of something extraordinary, or something else. We're digging.

posted May 23, 2006 | link | jump to the comments (6)

comments

Wolpe's comment, "See, they really are alive in there," is revolting. They really are alive.

- by Wesley J. Smith on May 24, 2006 at 1:11 AM | link

There is always the potential to study whether Ambien or something like it could be used long-term to restore consciousness. Or, yeah, we could just put 'em down like stray mutts as "Dr." (of sociology, per his bio) Wolpe "prescribes" and be done with it.

- by craig on May 24, 2006 at 6:31 PM | link

You are right that there is reason to be skeptical about these reports.
Beyond your comments, 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 describe one patients 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 wasnt 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. Theyre 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!? Its 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. Its 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 Sackss 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 its still hard to imagine a mechanism for these reports.
Time will tell, but my expectation is it will turn out to be false.

- by Kevin T. Keith on May 24, 2006 at 6:44 PM | link

Not sure if all of these are directly related, but there are more articles on the topic going back to at least 1976. For a sample, go to PubMed and enter the following unique identifiers (one at a time): 1290558, 1635936, 2152443, 397581, 815813.

- by TSH on May 24, 2006 at 7:55 PM | link

There are more articles that may be related going back to at least 1976. For a sample, go to PubMed and enter the following unique identifiers (one at a time): 1290558, 1635936, 2152443, 397581, 815813.

- by TSH on May 24, 2006 at 7:59 PM | link

While The Guardian is not an academic journal, this article bears reading

"Something strange and wonderful is happening here, and we have to get to the bottom of it," he says. "Since Louis, I have treated more than 150 brain-damaged patients with zolpidem and have seen improvements in about 60% of them. It's remarkable."

One doctor gaining a 60% rate over 150 patients where patients improve from treatment is a bit better than n=3
Now a GP is not a research scientist but somebody ought to at least get consent forms and analyze those 150 charts.

- by TM Lutas on Sep 15, 2006 at 8:46 PM | link