Issue with benzodiazepines not working

[Jwright1984]

I have been diagnosed with generalized anxiety disorder, panic disorder and ptsd. Within the last year I have been prescribed several different benzodiazepines. The problem I have? They don't work.....at all. A good example. I was prescribed diazepam 5 mg. I took it and felt...nothing. No anxiety relief, no sleepiness, no effects at all. Doc said to double it. I did, took 10 mg. Exact same thing. Doc said to try 20 mg. I did, took 20 mg. Again...nothing. I might as well have taken a sugar pill. We tried ativan with the same results. We tried Xanax with the same result. Even Ambien doesn't have any effect. I can't find anything online about anyone else having this issue. It can't be a tolerance issue because before the diazepam it had been over a year since I took a benzo and I only used it for 1 week at a low dose. At first I thought maybe my gabapentin was interfering, it does, sort of, work with the gaba system. I am off gabapentin now and have been for over a month and still my diazepam has no effect. I can take 20 mg and be wide awake with a completely clear head (albeit with anxiety raging). The only other med I take that involves the gaba/glutamate system is lamotrigine, could that be the culprit? This is very frustrating because if I get a panic attack, which can happen out of the blue for me, I have nothing I can take to quell it. If anyone can help or has information it would be greatly, greatly appreciated.

My current meds/supplements:

Fluoxetine 20 mg
Duloxetine 60 mg
Lamotrigine 200 mg
Modafinil 200 mg
Lansoprazole 15 mg delayed release
Valerian 1000 mg (for occasional insomnia)
Omega-3 3000 mg
Whole food multivitamin
Vitamin D3 5000 iu
Magnesium 350 mg

[Paxiled]

First, if you take a benzo, you have to stop the valerian -- they both target the same neurotransmitter (now, if you really know your herbs, if you take the valerian far apart in time from the time you take your benzo, you can do it, but nobody not very well educated about herbs should take valerian and a benzo.  Second, when do you take your magnesium?  Benzos and antidepressants and other drugs that target brain neurotransmitters use the magnesium pathway to get past the blood/brain barrier.  If you take your magnesium at the same time as you take your med, only one is going to get where it's trying to go.  This is why so many people who take antidepressants get muscle pain and problems with digestion -- they're often interfering with the absorption of magnesium.  Third, you're on a lot of drugs with so many possible contraindications, including ones nobody has discovered yet, that for you it might be a problem.  This is a problem for anyone who takes a lot of medication.  Fourth, gabapentin, is GABA, it's not like GABA (though of course it is synthetic).  It's formulated to go straight to your brain so it completely bypasses the digestive system, which probably avoids the magnesium problem.  But it might have burned out your GABA receptors -- it's the reason so many people who take this drug have to keep upping the dose and then it taps out.  Can't say this happens, but it's possible.  Now, none of these could be happening -- it might be your liver metabolites or some other protective agent in your body just don't like benzos.  It happens.  But there are a lot of benzos out there to try.  You might be looking for more from them than they can deliver given how many drugs you've been on, nor are they sleep aids --  they interfere with REM sleep and any drug taken for insomnia will eventually cause rebound insomnia.  The only cure for it is to get rid of the cause of it, which I admit is really really hard to do. If you really just can't sleep with the help of melatonin or exercise or meditation or lifestyle changes or natural remedies, take a sleeping pill, not a benzo.  I wonder if you had your blood checked to see if the benzos you took were successfully building up in your system?  One other idea -- taurine, a pseudo-amino acid, along with B6 is what the body uses to make GABA.  Taking GABA as a supplement generally doesn't work, because it usually doesn't successfully cross the blood/brain barrier.  That's one of the reasons neurontin and Lyrica became so popular.  But you might find benefit, as long as you're not on a benzo, from taking some taurine along with your valerian or, better, kava or passionflower, and see if it helps.  You obviously have a pretty severe problem so I don't know how much this will help, but since you're taking this stuff and it isn't working, it's worth a try.  Most times combining relaxants works better than taking one alone -- valerian works better taken with hops and passionflower, for example, than by itself.  But with kava, because you're on so much medication, a few people reported liver problems with it, so make sure if you try it you're other meds don't present that problem and you don't use the standardized version of it.  I found kava to be the closest thing in nature to a benzo.  Good luck.

[Jwright1984]

Gabapentin isn't actually GABA, it is similar in structure but binds to GABA receptors in a negligible amount. As far as magnesium and valerian, these are new and have never been taken with a benzodiazpine. The thing is, I took benzo's last year and they worked like they should. Something in the last year has caused them to stop working and I have no clue as to what or why. Ironically, Valerian also doesn't seem to have any effect but I was told you have to take it for several months to see any benefit so that is what I am doing. As far as taking passionflower I was advised to stay away from this as many species contain  beta-carboline harmala alkaloids of which some are MAO inhibitors which shouldn't be taken with SSRI's so that is out of the question. As far as sleep, I was only prescribed Ambien once but I don't take benzo's for sleep. Mostly I have them for anxiety/panic. As far as my current meds, I don't take any inducers of the liver enzymes responsible for metabolizing benzodiazepines, in fact I actually take some inhibitors of those liver enzymes so certain benzo's, like Diazepam, should actually be made stronger and more effective. I've researched this heavily and there are no obvious answers. The strange thing is I can't find a single reference to anyone else having this same issue. The whole situation is frustrating.

[Paxiled]

I seriously doubt passionflower has any measurable amount of MAO inhibition -- if it did people would have stopped taking it centuries ago because they relied so much on fermented foods and beverages.  If you buy from a reputable supplier, such as Herb Pharm, they aren't using different species, they're using the one that has shown to work over the centuries.  While gabapentin isn't the same as GABA, it was invented to look to the brain just like GABA and it does look almost the same chemically.  It's also true nobody knows why it works, so there's that.  Valerian doesn't need to build up in your system, but it doesn't work for everyone.  The problem when you've taken pharmaceutical products is, they've studied what plants do and made something synthetic that does it but is so much stronger that an herb might be working but you might not notice it for awhile.  Valerian never did anything for me by itself, but when I needed a boost for my meds, instead of taking more benzo, which I thought was more dangerous, I would take a combination remedy that combined passionflower, hops, kava, valerian.  This did work.  But I managed health foods stores for 18 years and in those days the herbalists and naturopaths who formulated natural medicines would come around all the time and train us and we had the books they had written and studied them before we were allowed anywhere near a customer about supplements.  A lot of what we read about natural medicine isn't accurate, it's theoretical, based on small bits of research here and there.  Because they can't be patented, there just isn't the money to do significant research.  One of the more interesting ones to research is St. John's Wort.  Originally, allopathic docs told everyone not to take it because it was an MAO inhibitor.  It wasn't.  The Germans in their Commission E research decided it had to be standardized for a substance called hypericin for it to work.  That turned out to be the wrong marker chemical.  Now they just admit they have no idea how it works, because plants are just too complex -- they contain so many different substances they are painfully difficult to study.  St. John's Wort was mostly used as an anti-viral until more modern usage as an anti-depressant, which shows just how complex herbs are.  Because we know all drugs are toxic to some extent and that the body doesn't know how to deal with them since they're not food, they are also difficult to use and unpredictable, but we use them anyway.  In your case, given you're reached an impasse for unknown reasons, that's why I think a trial with natural medicine couldn't hurt, but it's also why I'm dubious it will work for you because your brain is now so used to very strong drugs, like mine is.  When I mentioned liver metabolites, there is a class of psychiatrist called a functional physician -- they practice medicine as well as just psychiatry.  One of the things they test for is liver metabolites, because it's one indicator of whether a drug will be absorbed or rejected.  So basically, I just threw a kitchen sink at you, hoping if you see a naturopath or a functional physician who practices integrated medicine you might find answers you're not getting now.  I wish I had some, but I don't, I only know different benzos work differently on me and Xanax made me more anxious, not less, but whatever they use when I've had surgery works just fine, thankyou.  We just process this stuff differently.  Here's hoping you figure out this pickle, and it is a pickle.  It's very very hard to combine natural remedies with medication and both have it do what you want and not harm yourself.  Most practitioners of natural medicine prefer their patients get off drugs before treating them, but that's virtually impossible these days so they've had to adapt and work in teams.  That's the future trend, I hope.  Again, best of luck to you.

[Jwright1984]

During the instances I have used passionflower I have had to stop due to significant, and in one instance, dangerous increases in blood pressure. I know this can happen with an SSRI and MAO inhibitor. Now whether my problem was an SSRI MAO interaction I can't say. I just know what the effects have been in me. I've tried to use passionflower at least half a dozen times while on different medications and ended up with the same outcome, some worse than others.

[Paxiled]

That's that, then -- any time you get a bad reaction from taking an herb you shouldn't take it.

[WSH]

Modafinil is a stimulant and could be causing anxiety.