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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by cache-monkey on March 29, 2005, at 13:09:27
Hey all,
I'm going to be adding Depakote to my current low-dose (too low, really) Valium monotherapy.
The PI for Depakote states, regarding the interaction between Depakote and Valium:
"Valproate displaces diazepam from its plasma albumin binding sites and inhibits its metabolism. Co-administration of valproate (1500 mg daily) increased the free fraction of diazepam (10 mg) by 90% in healthy volunteers (n=6). Plasma clearance and volume of distribution for free diazepam were reduced by 25% and 20%, respectively, in the presence of valproate. The elimination half-life of diazepam remained unchanged upon addition of valproate."I'm not quite sure what this means. If anyone can explain, I would be much obliged.
Best,
cache-monkey
Posted by Ritch on March 29, 2005, at 13:41:33
In reply to Confused Re: Interaction btw. Valium Depakote, posted by cache-monkey on March 29, 2005, at 13:09:27
> Hey all,
>
> I'm going to be adding Depakote to my current low-dose (too low, really) Valium monotherapy.
>
> The PI for Depakote states, regarding the interaction between Depakote and Valium:
> "Valproate displaces diazepam from its plasma albumin binding sites and inhibits its metabolism. Co-administration of valproate (1500 mg daily) increased the free fraction of diazepam (10 mg) by 90% in healthy volunteers (n=6). Plasma clearance and volume of distribution for free diazepam were reduced by 25% and 20%, respectively, in the presence of valproate. The elimination half-life of diazepam remained unchanged upon addition of valproate."
>
> I'm not quite sure what this means. If anyone can explain, I would be much obliged.
>
> Best,
> cache-monkey
Maybe Ed can clarify better, but it sounds like the Depakote is going to boost the serum plasma level of Valium considerably because it will "displace" the Valium from "binding" to proteins-- I think the clinical effect is reduced when it is "bound" to proteins, when it is "displaced" by the Depakote it "frees" it up and the clinical effect of the Valium is increased. I think. Hope this helps.
Posted by Phillipa on March 29, 2005, at 17:17:17
In reply to Re: Confused Re: Interaction btw. Valium Depakote » cache-monkey, posted by Ritch on March 29, 2005, at 13:41:33
Why can't they talk in English! Fondly, Phillipa
Posted by ed_uk on March 29, 2005, at 19:37:57
In reply to Confused Re: Interaction btw. Valium Depakote, posted by cache-monkey on March 29, 2005, at 13:09:27
Hello!
Here is the original abstract...........
Br J Clin Pharmacol. 1982 Apr;13(4):553-60.Valproic acid and diazepam interaction in vivo.
Dhillon S, Richens A.
1 The effect of oral administration of sodium valproate (1500 mg daily) on the distribution and elimination kinetics of intravenously administered diazepam in six healthy volunteers has been studied. 2 During valproate administration the unbound fraction of diazepam in serum increased approximately two fold. This was accompanied by a significant increase in apparent volume of distribution and plasma clearance of diazepam. 3 There was a positive correlation between the change in free fraction and the increase in both apparent volume of distribution and plasma clearance of the drug. 4 The concentration of unbound diazepam in serum (calculated from the percent free diazepam and total serum concentration) was significantly higher during valproate administration. Both the intrinsic clearance and volume of distribution of unbound drug were significantly reduced. 5 Mean serum N-desmethyldiazepam levels were significantly lower during valproate coadministration. 6 These results suggest that valproic acid displaces diazepam from plasma protein binding sites and inhibits its metabolism.
....................................................
>I'm not quite sure what this means. If anyone can explain, I would be much obliged.
I was thinking you were currently cross-tapering from alprazolam to diazepam. .....Or are you just taking diazepam at the moment?
Depakote may affect the dose of Valium which you will require. Although Depakote increases the concentration of unbound diazepam in the serum, it also decreases the concentration of diazepam's pharmacologically active metabolite: desmethyldiazepam. As a result, it's very difficult to predict what effect Depakote might have on the dose of diazepam that you will require. Because of Depakote's mood stablising properties, I think it's most likely that Depakote will minimise the amount of diazepam that you will need.
The Depakote dose may also affect the amount of diazepam that you will require. You may need to adjust the amount of diazepam that you're taking when the Depakote dose is changed.
If, after you've spent some time on Depakote, you decide that you no longer want to take it, you may need to adjust your diazepam dose again as you taper the Depakote.
In short, Depakote may affect the amount of diazepam that you require. The amount of diazepam that you will need is likely to depend on the amount of Depakote that you are taking.
There are two types of interaction between diazepam and Depakote....
1. Pharmacokinetic
Depakote displaces diazepam from plasma protein binding sites, increasing the serum concentration of unbound diazepam. As a result, the amount of diazepam reaching the brain will be greater.
Depakote inhibits the metabolism of diazepam- reducing the serum concentration of diazepam's major active metabolite.
2. Pharmacodynamic
Depakote and diazepam may have addictive effects on the brain eg. increased drowsiness, reduced coordination etc.
In the short term, I would expect Depakote to decrease the amount of diazepam that you will need.
After diazepam has been taken for several weeks, it's metabolite desmethyldiazepam is responsible for a large proportion of the drug's sedative-anxiolytic activity. Since Depakote appears to reduce the blood level of desmethyldiazepam, the (probable) potentiating effect of Depakote on diazepam may be less pronounced in the long term. This is just a theory- desmethyldiazepam has a much longer half-life than diazepam so it tends to accumulate.
Here is my advice.......
Once you've started Depakote, don't feel you have to take exactly the same dose of diazepam every day. Adjust your daily diazepam dose according to the severity of your anxiety. When you're eventually on a stable/constant dose of Depakote, you'll be able to find a suitable maintenance dose of diazepam. If the Depakote works really well, you might not even need the diazepam anymore!
Best,
Ed.
This is the end of the thread.
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