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Ryan-could use your expertise
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Ryan-could use your expertise

I've taken valium for 5 years and never really had much side effects from it. However, since taking zoloft I feel more side effects from the diazepam such as more drowsy, dizzy, headache, etc. I looked for interactions and I did come up with something that is known. This is what I've found:

In a study consisting of 20 healthy male volunteers, pretreatment with sertraline (50 mg/day titrated to 200 mg/day over 10 days) for 22 days was associated with a 32% decrease in the systemic clearance of diazepam (10 mg single intravenous dose) relative to baseline, compared to a 19% decrease relative to baseline for the placebo group. There was no significant difference in the pharmacokinetics of N-demethyldiazepam, a major pharmacologically active metabolite of diazepam, before and after sertraline administration except for the time to reach peak plasma concentration (Tmax), which increased by 23% in the sertraline group and decreased by 19% in the placebo group. The clinical significance of these changes is unknown but should be minimal. However, caution is recommended during concomitant administration, as the risk of using sertraline with other CNS-active drugs has not been systematically evaluated.

So from my understanding Diazepam does not leave the system as fast when dosing with zoloft and even maybe more important is that N-demethyldiazepam actually reaches peak plasma levels quicker by a significant amount compared to placebo. What does this mean exactly? Does this mean that the N-demethyldiazepam is building up too much in the blood hence more side-effects. I just feel aweful after I take a valium and don't remember feeling that way on it with previous ssri's like lexapro, paxil, etc. Can you give me some insight and more explanation in plain English so I can make a decision on what to do. Thanks.
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P.S.
I also found something with combining luvox with valium and was wondering if zoloft is similar to luvox in it's action. Here's what I found:

The co-administration of Fluvoxamine Tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic co-administration. Evidence supporting the conclusion that it is inadvisable to co-administer fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (R= B), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study. It is likely that experience significantly underestimates the degree of accumulation that might occur with repealed diazepam administration.

If the same holds true with Zoloft then it may be wise for me to either switch benzo or go to paxil which is my next choice. Your advice would be appreciated.
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Avatar_n_tn
Might as well get all my questions out of the way :)

Would paxil be a good substitution if I wanted to stick with Diazepam?
Would klonopin be fine to take with the Zoloft?

I noticed there was a buildup with diazepam and also of zoloft when taking with Grapefruit which gives me some indication that taking zoloft and diazepam is really causing me some problems.
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Wish I could edit my posts. Sorry about the add-ons.
Something else I ran across is that paxil, zoloft, and prozac greatly increases diazepam levels by altering it's clearance. Therefore, I don't know if paxil would really be an answer or a good alternate to the zoloft. Clonazepam interacts or interferes with the CYP3A3 and and 3A4 enzyme substrates so not sure if that would still give me the same problem with zoloft or paxil. I really prefer the valium but am open at this point. Just need some advice and clarification in plain English. Thanks again.
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Avatar_n_tn
While your digging I'll give you a little more info on my situation.

I take ssri's specifically for worrying obsessively about my health and a little ocd. I also have generalized anxiety disorder. I probably have bi-polar also since the ssri's tend to make me manic at times as well. However, the ssri's are the only thing that works that helps me to function normally without constantly worrying about my health. They are stimulating to me which is a problem and prozac, effexor were the worst. Paxil and Lexapro have seemed to be the most tolerable. Zoloft is one I have never really given more than a few weeks. I have been on remeron, celexa, lexapro, paxil, zoloft, luvox, and I'm sure I'm missing a few more.

The problem my doctor has is that we know the ssri's are stimulating but it is the only thing that works for my obsessions with my health. Looking back I've had ocd behaviors since I was a child. The benzo's have been something I always stay on whether I am taking ssri's or not for my GAD. I took klonopin for 8 years then switched to valium and like it much more. It makes me feel more like myself where the klonopin dulls me and gives me more of a buzz and makes me out of it.

Again, zoloft is the one ssri that I have never given longer than a few weeks on compared to the others so that's why we are trying it out. The lexapro stopped working and paxil I was on a few times for years at a time so that's why my decision to go back to it is an option. However, since taking the zoloft I feel aweful while taking the valium. Usually an hour or two after popping a valium I feel horrible. I am guessing that there is some type of interaction between the 2 and from what I am reading the studies suggest that. However, it also suggests that paxil and prozac does the same but there is not as much literature on it and I do not recall feeling so bad when I took the valium and the paxil together.

My dilemna is that I want to give the Zoloft some time to work since it's one I have never fully given time to work but I don't want to keep dosing the 2 if they are causing adverse reactions or side effects that I can avoid if I switch one of them. At this point it's either switch to klonopin and stick out the zoloft or switch to paxil and stay on the valium but I wanted your input on the interactions. My girlfriend say's I've been complaining non stop since taking the zoloft and valium together but it's hard to pinpoint which one is making me feel bad. My conclusion that it's probably the 2 together because I tend to feel the worst after I take the valium. I take the Zoloft in the morning and can really wait until 4 or 5pm before I feel the need to take a valium. When I do take it I feel out of it, sick, dizzy, buzzed, and that's just at 5mg-hardly a large dose. After 4 or 5 hours I start to feel better. It's difficult to contribute to the valium because I've taking it for so long with no problems and I feel fine in the morning after taking the zoloft except for the normal stimulation and typical side effects I get with pretty much any ssri I've taken.

Anyways, the enzymes is what has got me thrown for a loop. I'm just not educated on it but it seems that there is a known interaction between zoloft and valium and I am thinking that taking zoloft with valium is causing a build-up of diazepam and it's major metabolite hence more interactions and it could be causing more zoloft build-up as well. I'm just not sure. Thanks.
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P.S.
I've been on Zoloft for 5 weeks today...started out at 50mg and last 2 1/2 weeks at 75mg so I did expect some side effects but I didn't expect them with the valium and didn't really attribute it to the valium and was looking at the zoloft also as the problem until I read up on the interactions. The lingering questions again are:

1) Is there an interaction between zoloft and diazepam that would warrant me to consider switching one? If so, in your opinion would paxil be a viable alternative even with some literature stating that paxil causes increases in diazepam levels hence putting me in the same situation?
2) If I switch to klonopin is it known to have the same interactions of buildup of clonazepam when dosed with zoloft or paxil. I know there are no active metabolites  but didn't know if there are interactions similar to dosing klonopin as there would be with diazepam.
Your a big help and I appreciate any feedback or opinion to help aid me in my decision. Thanks.

I think I just may be drugging myself up too much by taking both causing either a buildup of diazepam or zoloft or both.
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Avatar_n_tn
Ryan,
What would make you believe that paxil would not have the same effect as Zoloft since it's a potent inhibitor of CYP2D6 as well. Is there something you found that would indicate why paxil and zoloft would have different effects on valium clearance? I have found no such thing except one article which states that paxil will alter the clearance of valium but that's all I could find. Paxil's literature states that valium does not effect paroxetine but the effect of paroxetine of diazepam was not evaluated. This leads me to believe there may be similar interactions with paxil and valium but just haven't been established like with Zoloft. Could this be true? The reason I'm asking is because I don't want to switch over to paxil after being on zoloft for a while and just end up in the same position. Thanks again.
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