Searching for published papers/Neurontin

[craig]

I'm looking for something published in any medical Magazine/Journal
on the use of Neurontin in large dosages on humans. Above 2500 mg a day.
I'm at 3000 mg and my local doctor has been told 2400 mg is Max! Any ideas? Perhaps I'm not using the search in the right way here.
Thanks for any help.

cbal-craig

[Max]

Is it same drug as Gabapentin?

Here is interesting article about lowering dose

http://www.newscientist.com/news/news.jsp?id=ns9999156


Try search on this website both Doctors guide & Medline

http://www.docguide.com/dgc.nsf/ge/Unregistered.User.545434?OpenDocument


Hope this helps

[This message was edited by Max on Dec 02, 2002 at 03:33 PM.]

[craig]

Thank you Max,
I have spent an hour or so and it appears not much has been published about large dose usage. I'll keep looking though, thanks for the links.

craig

[David Berg]

You also might try searching on PubMed at http://www.ncbi.nih.gov/entrez/query.fcgi
or
http://www.pubmed.com

There was a story awhile back on NPR about the company that originally had Neurontin before Pfizer acquired it a few years back. Among other things, they mentioned that the company was pushing doctors to prescribe up to 4800 per day.

Regardless of the dosage (but especially with the higher dosages), be sure to familiarize yourself with the possible problems that can arise with Neurontin and pay attention to your body while you're taking it. It's a drug that's helped lots of people, but it's a powerful drug and has a few potentially dangerous side effects. You can read Pfizer's own info on Neurontin at:
http://www.pfizer.com/hml/pi%27s/neurontinpi.pdf

David Berg

[Wise Young]

Here are some recent articles... Sorry, I don't have time to review the literature for you right now.

• Arroyo S (2002). [Titration and dosage of gabapentin]. Rev Neurol 34:287-9. Summary: INTRODUCTION. Gabapentin (GBP) is a new anti epileptic drug which is indicated in partial epilepsy as either monotherapy or additional therapy. Unlike most anti epileptic drugs, GBP can be rapidly titrated. DEVELOPMENT. A recent double blind trial has shown that treatment with GBP may start with 900mg from the first day (300 mg every 8 hours). This dose is sufficient to be effective as monotherapy in patients with partial epilepsy of recent onset. It is also known that in patients with drug resistant epilepsy high doses of anti epileptic drugs are often necessary. In the clinical trials carried out before gabapentin was put on the market, the doses used were generally low (almost always below 1,800 mg/day). However, recent experience has shown that doses of up to 4,800 mg/day markedly increase the efficacy without significant increase in the rate of adverse effects. CONCLUSIONS. Recent data suggest that GBP may be rapidly titrated and high doses of GBP show greater efficacy with no increase in adverse effects, so they are advisable in drug resistant patients. Department of Neurology; Institut Clinic de Malalties del SN, Barcelona, 08036, Espana. santiago.arroyo@terra.es
• Kang MG, Felix R and Campbell KP (2002). Long-term regulation of voltage-gated Ca(2+) channels by gabapentin. FEBS Lett 528:177-82. Summary: Gabapentin (GBP) is a gamma-aminobutyric acid analog effective in the treatment of seizures. A high-affinity interaction between GBP and the alpha(2)delta subunit of the voltage-gated Ca(2+) channels has been documented. In this report, we examined the effects of the chronic treatment with GBP on neuronal recombinant P/Q-type Ca(2+) channels expressed in Xenopus oocytes. GBP did not affect significantly the amplitude or the voltage dependence of the currents. Exposure to the drug did, however, slow down the kinetics of inactivation in a dose-dependent fashion. In addition, biochemical analysis showed that the integrity of Ca(2+) channel complex is not apparently affected by GBP binding, suggesting that chronic treatment with the drug might cause the channel kinetic modification through subtle conformational changes of the protein complex. Howard Hughes Medical Institute, Department of Physiology and Biophysics, The University of Iowa College of Medicine, 400 Eckstein Medical Research Building, Iowa City 52242, USA.
• Mellegers MA, Furlan AD and Mailis A (2001). Gabapentin for neuropathic pain: systematic review of controlled and uncontrolled literature. Clin J Pain 17:284-95. Summary: OBJECTIVE: To assess the efficacy/effectiveness and side effects of gabapentin for the treatment of neuropathic pain. DESIGN: Systematic review of the literature. METHODS: Extensive search of several electronic databases located both controlled and uncontrolled studies. Efficacy was assessed through meta-analysis of randomized controlled trials (RCTs), whereas the effectiveness of gabapentin in uncontrolled studies was assessed via a novel system of dichotomous classification of "bad" versus "good" results. FINDINGS: Thirty-five papers involving 727 patients with multiple neuropathic pain conditions met the inclusion criteria. The meta-analysis of the 2 high-quality, placebo-controlled RCTs showed positive effect of gabapentin in diabetic neuropathy and post-herpetic neuralgia. The addition of 2 low-quality, placebo-controlled RCTs did not alter the magnitude or direction of observed effect. The uncontrolled studies demonstrated positive effect on pain in different neuropathic syndromes, as well as benefit on different types of neuropathic pain; highest dose administered and rate-of-dose escalation showed wide variability between prescribers. Fewer and less severe side effects were reported in the uncontrolled studies. CONCLUSIONS: Gabapentin seems to be effective in multiple painful neuropathic conditions. The variable prescribing patterns of the uncontrolled studies raise the suspicion that effectiveness may be reduced if one limits administration of the drug to very low doses, whereas rapid dose escalation may be associated with increased central nervous system side effects. Well-designed controlled trials may provide insight into differential symptom sensitivity to the drug. University of Maastricht, The Netherlands.
• Sutton KG, Martin DJ, Pinnock RD, Lee K and Scott RH (2002). Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol 135:257-65. Summary: 1. This study examined the action of gabapentin (gabapentin,1-(aminomethyl) cyclohexane acetic acid (Neurontin) on voltage-gated calcium (Ca(2+)) channel influx recorded in cultured rat dorsal root ganglion (DRG) neurones. 2. Voltage-gated Ca(2+) influx was monitored using both fura-2 based fluorescence Ca(2+) imaging and the whole-cell patch clamp technique. 3. Imaging of intracellular Ca(2+) transients revealed that gabapentin inhibited KCl (30 mM)-evoked voltage-dependent Ca(2+) influx. Both the duration for 50% of the maximum response (W50) and total Ca(2+) influx were significantly reduced by approximately 25-30% in the presence of gabapentin (25 microM). 4. Gabapentin potently inhibited the peak whole-cell Ca(2+) channel current (I(Ba)) in a dose-dependent manner with an estimated IC(50) value of 167 nM. Block was incomplete and saturated at a maximal concentration of 25 microM. 5. Inhibition was significantly decreased in the presence of the neutral amino acid L-isoleucine (25 microM) but unaffected by application of the GABA(B) antagonist, saclofen (200 microM), suggesting a direct action on the alpha(2)delta subunit of the Ca(2+) channel. 6. Gabapentin inhibition was voltage-dependent, producing an approximately 7 mV hyperpolarizing shift in current voltage properties and reducing a non-inactivating component of whole-cell current activated at relatively depolarized potentials. 7. The use of specific Ca(2+) channel antagonists revealed a mixed pharmacology of the gabapentin-sensitive current (N-, L- and P/Q-type), which is dominated by N-type current. 8. The present study is the first to demonstrate that gabapentin directly mediates inhibition of voltage-gated Ca(2+) influx in DRG neurones, providing a potential means for gabapentin to effectively mediate spinal anti-nociception. Department of Biology, Pfizer Global R&D, Cambridge Laboratories, Cambridge, CB2 2QB. Kathy_sutton@merck.com

[craig]

Thank you very much David and Dr. Young

[David Berg]

craig,

I neglected to clarify that 4800 is a high dose and I'd be very wary of going that high. Even the NPR show didn't portray the company's actions (such as recommending such high doses) as favorable.

Before Pfizer took over, the prior company (I can't recall their name off-hand) used a number of questionable marketing tactics. You might even be able to go to http://www.npr.org and do a search on Neurontin and find that story in their archives.

David Berg

[craig]

Originally posted by David Berg:

craig,
I neglected to clarify that 4800 is a _high_ dose and I'd be _very_ wary of going that high. Even the NPR show didn't portray the company's actions (such as recommending such high doses) as favorable.
David Berg

No problem there, I am trying to dose down to 2800 mg or even 2500 however the burning is very tough to endure. I also use strong narcotics for chronic skeltal pain when needed. It is an effort to keep my eyes open from all the Neurontin, I plan to go see my Neurologist to see about other anti-convolution meds. I understand they are using a couple of other drugs.

Thanks ~