Personalized Clonazepam Therapy and Withdrawal Regimen (CYP3A4 and NAT2 Enzymes)

Optimization of Clonazepam Therapy Adjusted to Patient’s CYP3A Status and NAT2 Genotype

"Prospective assaying of CYP3A4 expression and N-acetyl transferase 2 acetylator phenotype can better identify the patients with higher risk of adverse reactions and facilitate the improvement of personalized clonazepam therapy and withdrawal regimen."

"A careful and protracted withdrawal regimen can be suggested to apply for normal CYP3A4 expresser patients with slow NAT2 acetylator phenotype to avoid withdrawal symptoms or to minimize the severity of symptoms. Nardi et al. (2010) recommended a 0.25-mg/wk rate of dosage reduction after intermediate-term use of clonazepam; however, the potential benefits of personalizing discontinuation are worthy of investigation."

Full study here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203763/

Thanks for posting this article, abcd! I know they're looking at a very specific population in this study, but the information is still very pertinent and interesting to me. How did you happen to come across it?

Hey, Lapsy.  Specific population?  Meaning those diagnosed with schizophrenia or bipolar?  I can't imagine that would have any impact on this particular study, though.

How did I find it?  One click leading to another, lol.

Hey abcd,

There's a mention of the other medications the people are taking concurrently with clonazepam, so that can certainly play a role. It's mentioned in the article. Still, though, the premise is that people with certain genotypes metabolize clonazepam in such a way that they are more susceptible to the side effects and withdrawal effects of the medication. Concurrent medications can further affect the whole process.

Suffice to say, I asked someone to print this one out for me, so it's going in my file as one to keep as a reference. So, thanks again for sharing it!

Hey Lap, I see where you're coming from, yes, those other meds are always a complicating factor.  Ya know, although I understand the importance of these types of studies, still, I felt so bad for the poor participants.  :'(

I'll be sure to post if I stumble upon more of these such studies. 

Thanks very much, abcd. I just think it's important to have proof of how different people are when it comes to reactions to benzos. If a doctor says, "Well, I've got other patients on this, and they're fine," or "Your reaction is more extreme than most," or something like that, a study like this can explain what's going on. Genotypes play a major role in medication metabolism, and all doctors and pharmacists should understand that.

If I'm understanding correctly, the patients weren't on clonazepam for very long. So, take heart, dear abcd!

Optimization of Clonazepam Therapy Adjusted to Patient’s CYP3A Status and NAT2 Genotype

"Prospective assaying of CYP3A4 expression and N-acetyl transferase 2 acetylator phenotype can better identify the patients with higher risk of adverse reactions and facilitate the improvement of personalized clonazepam therapy and withdrawal regimen."

 

"A careful and protracted withdrawal regimen can be suggested to apply for normal CYP3A4 expresser patients with slow NAT2 acetylator phenotype to avoid withdrawal symptoms or to minimize the severity of symptoms. Nardi et al. (2010) recommended a 0.25-mg/wk rate of dosage reduction after intermediate-term use of clonazepam; however, the potential benefits of personalizing discontinuation are worthy of investigation."

 

 

fascinating, thank you

Full study here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203763/

Benzodiazepine Kinetics -  Comparison Chart

http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?19/60/20425

Good info and more charts here on CYP3A4 inducers/inhibitors/substrates:

http://www.pharmacytimes.com/publications/issue/2008/2008-09/2008-09-8687