Posted by Jeff Berk; BOLT International
Typical mooring at the Scottsdale Yacht Club.
I take Lyrica*
It’s a party in a pill
Friends inside my head
* (This is a Haiku. It’s NOT a true confession. I take martinis. Now there’s a true confession)
Funk-Sway; noun; the positive effect that pregabalin has** on the brain’s interior design.
(** You’re probably wondering how I know this)
Lyrica (pregabalin; Pfizer)
- The mechanism of action of pregabalin in fibromyalgia s believed to decrease substance P release at the synapse of peripheral neurons with central neurons.
“Drugs that are beyond the pipeline I can identify and I am sure that Eli Lilly and Pfizer but it wasn’t really Pfizer, it was before Pfizer took over pregabalin from Parke-Davis. So Pfizer bought Parke Davis to get Pregabalin. But Parke-Davis, we had published our results on substance P long before they started thinking about pregabalin and so they called me and asked me to come because they said we wonder if this might work in fibromyalgia. And, in fact, the mechanism of action of pregabalin is believed to decrease substance P release at the synapse of peripheral neurons with central neurons or interneurons. So it was logical that agent might be helpful in people with fibromyalgia who have high substance P levels. There will be experiments to evaluate that question and playing out whether it is true or not but it is true in animals. If you treat an animal with pregabalin they produce less substance P”.
- Pregabalin facilitates some of the deep first stages of sleep. No one has ever tested to see whether growth hormone production or insulin-like growth factor is increased with pregabalin therapy, but this is the mechanism by which Xyrem (sodium oxybate) produces its analgesic benefit.
“…Stage 3 or 4 non-REM sleep that occurs with sodium oxybate and it doesn’t stimulate growth hormone production which is a big problem in fibromyalgia, the growth hormone production is low because the are not getting into deep stages of sleep. Sodium oxybate provides that sleep stage of sleep and has been shown to stimulate growth hormone. Lyrica, pregabalin, also facilitates some of the deep first stages of sleep and no one has ever tested to see whether growth hormone production is increased or insulin-like growth factor is increased with pregabalin therapy”.
- Lyrica is effective in neuropathic pain and it is approved for fibromyalgia. The key benefits that Lyrica provides fibromyalgia patients is a 30%-50% reduction in pain and some improvement in fatigue. In order to move prescribers to switch from gabapentin to pregabalin Pfizer will try to make the case that pregabalin doesn’t negatively impact cognition as much as gabapentin. And since poor cognition worsens pain syndromes, the switch should have an overall positive effect on pain.
“We do (use Lyrica). We do use them for the standard problems like if you have an RA patient who is diabetic and has polyneuropathy or restless leg syndrome. We have used it or use it in fibromyalgia with limited success. Some patients like it because they can sleep a little bit better, but that is not a main breakthrough actually. None of the anti-fibromyalgia drugs are a real breakthrough. That is a very difficult field”.
“So the alpha-2 delta ligands certainly work in neuropathic pain. There is no question about that. And they are approved for fibromyalgia and there is no question about that. Getting the psychiatrists to use pregabalin vs. gabapentin will require some questions. They are more or less the same doses that get into the CNS. They have equally binding properties but obviously pregabalin is more potent because it gets in more reliably because it uses system L transporter and another transporter. Psychiatrists are very happy with gabapentin. Most of them can figure out pregabalin. It is just a newer version of that. Most of them have been using for a long time gabapentin off label for sleep, which can be a big problem in pain syndromes. They know it makes you tired in the daytime, which is the bad part of helping your sleep, and then therefore it makes cognition which is a part of these pain syndromes actually worse potentially. Whereas the SNRIs can make your sleep worse and your cognition better. So it wouldn’t take a rocket science in psychiatry to use them both together and hope you get these things fibro fog or these cognitive symptoms of pain treated with more of an SNRI and the sleep problems, the lack of slow wave sleep maybe gotten better by an alpha-2 delta ligand. So I think most psychiatrists are very capable of mixing and matching all the SNRIs with any of the alpha-2 delta ligands”.
“I expect from that drug to get a 30-50% reduction in pain and some improvement in fatigue due to better sleep. The short answer is burden. I think that none of these drugs put people into remission. They do for depression but not for pain. It takes the edge off. What tends to be is that it doesn’t bother them as much. So you don’t say is your pain gone because it almost never goes away, but what they say is that it doesn’t interfere as much because if they sleep better at night and they wake up more refreshed and they have less fatigue they can deal with it”.