Gabapentin Neurotoxicity

[xbnmx]

I was recently diagnosed with anxiety by a psychiatrist (or, rather, a nurse practicioner). She wanted to put me on SSRIs but I declined partially as a result of some things I've read, but largely as a result of some things I've seen them do to people I know who've gone on them. The only option aside from an SSRI, and I stress only, she said their was is a drug called gabapentin. I have done extensive research and found lots of sources that say the mechanism behind the drug is unknown, lots that say its a SGRI, and lots that specifically say its not an SGRI. i would like to have a better understanding of just what its mechanism on the brain is. Furthermore, I discovered a study (linked below) that I found this troubling paragraph in:

Our patient initially received 400 mg/day of gabapentin and developed absences. Gabapentin serum levels at that time were very high. This is in contrast to the suggestion by Verma et al. that gabapentin is extremely well-tolerated even in haemodialysis patients with high serum concentration [7]. Our pharmacokinetic study showed that even the recommended dose of 300 mg gabapentin [6] after each haemodialysis session was excessive and that the patient had very high serum levels. Gabapentin pharmacokinetic values in our patient differed from those previously reported by Wong et al. in haemodialysis patients [6]. However, the pharmacokinetic parameters of gabapentin in our patient should not be compared to those of Wong et al. since our patient was clearly overdosaged. At time 0 before administration, the parameters were already much higher than the Cmax of haemodialysed patients (6 mg/l) reported by Wong et al. [6] or in non-uraemic subjects (2.7 mg/l) after a dose of 300 mg. Furthermore, gabapentin is not metabolized and is entirely excreted in urine with a clearance that is linearly proportional to creatinine clearance. Consequently, in patients with terminal renal insufficiency accumulation of gabapentin occurs. Gabapentin is a highly hydrophilic compound which diffuses into adipose tissues only weakly. Therefore, excessive accumulation of the drug in plasma easily leads to a concomitant accumulation in cerebrospinal fluid and neurotoxicity. For these reasons, the dose of gabapentin was decreased in our patient to as low as 100 mg after each haemodialysis session. During the subsequent 4 months the patient experienced neither absences nor epileptic seizures.​

I was started on a pediatric dose of 600 mg a day (three 100mg pills three times a day and three 100mg pills before bed) that I worry, according to this study, could be accumulating in my cerebrospinal fluid and inciting neurotoxicity. Am I interpreting this correctly? Thank you for your time and help.

Study:
http://ndt.oxfordjournals.org/cgi/co...ull/16/10/2112

 

[David Baxter PhD]

The link in your post is broken...

However, I suspect it should be this one: http://ndt.oxfordjournals.org/cgi/content/full/16/10/2112

More information at Gabapentin Neurotoxicity - Google Search

But the bottom line is that we have a lot more experience with SSRIs, SNRIs, and their relatives than with the "neurotransmitter replacement" strategies, and therefore far m ore is known about the side-effects, risks, and long-term impact of the more commonly prescribed antidepressants.

I personally would be a little worried about beginning this type of therapy based on an evaluation by a nurse practitioner - no disprespect to nurse practitioners but I would be happier if you were doing it under the supervision of a psychiatrist and/or psychopharmacologist. It might be worth asking for a second opinion, if you're concerned.

 

[Daniel E.]

The only option aside from an SSRI, and I stress only, she said their was is a drug called gabapentin.

What about benzodiazepines (benzos) like Klonopin? Klonopin (clonazepam) was my favorite medication when I had problems sleeping due to anxiety. Exercise can also help a lot, and clinical studies have shown it to be as effective as medication for anxiety. So therapy + medication + exercise is ideal.

She wanted to put me on SSRIs but I declined partially as a result of some things I've read, but largely as a result of some things I've seen them do to people I know who've gone on them.

Personally, I tolerated even the older antidepressants like tricyclics and MAOI inhibitors pretty well. With most of the newer SSRIs I have taken like Lexapro, I have had no side effects at all. Worse come to worse, one just tritates down the dose and switches medications.

 

[xbnmx]

I asked about benzos and she said that they were out of the question due to addiction potential. She also stated that SNRIs were inappropriate. When gabapentin was the only drug offered as an alternative to an SSRI, she also mentioned that she had free samples of SSRIs, but not gabapentin. I am going to proceed to get a second opinion from an actual psychiatrist, its just it took months to get an aappointment with the one I did and then when they canceled day of all I had as a recourse was this nurse practitioner. Was your conclusion from the aryicle that my gabapentin therapy is, in fact, likely to be neurotoxic? Thank you again for your time and help!

 

[Daniel E.]

Since people undergoing dialysis are still given this drug -- though at a lower dosage -- toxicity doesn't seem to be a major concern for people with healthy kidneys:

Dosage adjustment in patients with compromised renal function or undergoing hemodialysis is recommended.

Adult Patients With Renal Insufficiency: Subjects (N=60) with renal insufficiency (mean creatinine clearance ranging from 13-114 mL/min) were administered single 400 mg oral doses of gabapentin...Dosage adjustment in adult patients with compromised renal function is necessary.

...This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.

http://www.pfizer.com/files/products/uspi_neurontin.pdf

Some anecdotal evidence (which is all over the place, but mostly reassuring):

Neurontin for Generalized anxiety disorder (GAD) Community Ratings - Revolution Health

Also: http://www.psycom.net/depression.central.gabapentin.html

 

[David Baxter PhD]

I asked about benzos and she said that they were out of the question due to addiction potential. She also stated that SNRIs were inappropriate.

SNRIs (Effexor, Cymbalta) are usually the treatment of choice these days for anxiety disorders, although arguably some people would do better on benzodiazepines.

A second opinion wouldn't hurt...

 

[xbnmx]

Can you articulate why benzos are preferable for some patients? Also, the article that I linked in the initial thread alarmed me to the point of not wanting to take my medication, can you help me to understand its findings if gabapentin is, as suggested above, not largely neurotoxic?

 

[Daniel E.]

Personally, the benzos were preferable for me because they actually worked. The SSRIs and SNRIs didn't seem to work for me, or, more accurately, whatever positive effects they had seemed too subtle. (I had drug-resistant depression/anxiety/OCD, which is why I tried MAOI inhibitors, tricyclics, etc.)

 

[David Baxter PhD]

See Some Concerns About Abuse of Benzodiazepines Unwarranted - Psychlinks Psychology and Self-Help Forum

 

[Daniel E.]

Also, the article that I linked in the initial thread alarmed me to the point of not wanting to take my medication, can you help me to understand its findings if gabapentin is, as suggested above, not largely neurotoxic?

Though your question is directed towards David, I would point out that the article in your original post is about a patient who is undergoing dialysis for renal (kidney) insufficiency. Since the kidneys were not working properly, they couldn't filter out the drug, which caused the drug to build up in the body to a toxic level. If your kidneys are healthy, I wouldn't worry about it.

 

[xbnmx]

Thank you both very much for your incredibly punctual and helpful input and advice!