Monday, March 16, 2009
What is the one drug taken by 85 percent of those with schizophrenia and two in three with bipolar that they are 100 percent compliant with?
I posed this question last year to 50 or 60 clinicians at a grand rounds lecture I presented at a psychiatric facility in Princeton. Just prior to asking the question, I cited a 2006 study in which four in five patients on Zyprexa dropped out of the long-term phase of the trial.
This is not an isolated finding. The drop-out rate figure fluctuates between 40-to-100 percent over the long term across a broad range of psychiatric meds and diagnoses.
What's different about nicotine? In my talk, I showed a slide citing the research of Robert Freedman MD of the University of Colorado that connected "auditory gating" disturbance to nicotine craving. Apparently, individuals with schizophrenia have trouble screening out the second of two repetitive sounds, which does hell to their concentration.
This gating response is mediated by - drum roll, please - the alpha-7 nicotinic receptor.
Nicotine works. With nicotine, patients actually get their brains back - even if just for a precious few seconds. Apparently, in the brief time a cloud is in the patients' lungs, a cloud clears from the brain.
The only thing that is wrong is the delivery system, but in the drug development pipeline are nicotinic agonists.
Here's where I won over my audience: "So, if you prescribe cigarettes," I said, "you will get much better compliance than if you prescribe an atypical antipsychotic."
(Clinicians like to show their appreciation by looking like they're holding in their lower intestinal tract versions of auditory gating.)
"Now, compare that with an atypical antipsychotic," I went on to say. "Rather than clearing the brain, these meds actually take major parts of the brain off-line."
For support, my slide quoted a 2007 editorial in the American Journal of Psychiatry:
"Without adequate dopamine signaling, our patients do not feel 'well.' When dopamine systems are dysfunctional, patients seek a change. This may involve stopping taking a medication, such as antipsychotic drugs that block dopamine."
Then I quoted John Krystal MD of Yale from a lecture he gave to the American Psychiatric Association the year before:
"Our medications are least effective for the most disabling symptoms of schizophrenia," namely, "the cognitive dysfunctions ..."
Cognitive dysfunction also looms large in bipolar.
Let's start connecting the dots: We have psychiatrists prescribing patients a class of drugs that work well against psychosis at the expense of worsening the most pronounced feature of schizophrenia and a significant feature of bipolar. No surprise - low compliance rates.
Meanwhile, we have a drug that doctors try to ban that actually helps bring patients' brains back online for a few precious seconds. Surprise, surprise - high compliance.
You tell me: Who are the smart people in this equation?
"Far from lacking insight into their illness, from refusing to put up with side effects," I said, "patients are willing to put up with a drug with one of the worst side effects profiles in the world. Why? Because it works. It works where they want it to work."
I was just getting warmed up:
"Let's face it," I said, "we've all been badly oversold on the new generation antipsychotics - you, me, family members. When all is said and done, these new generation atypicals are basically Thorazine with the tires rotated."
I wasn't through:
"The CATIE studies brought this out loud and clear. My question for you is why did it take you so long to figure this out? The same info was in the journals you subscribe to, on the labeling of the meds you prescribe. More important, your patients have been telling you this for years.
"Why haven't you been paying attention?"
This part of my talk was interrupted by a spontaneous display of stony cold silence. The temperature in the room literally dropped ten degrees.
What were they expecting? A CME lecture sponsored by Eli Lilly with free "Zyprexa" pens and coffee mugs?