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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by garyengelm on January 3, 2008, at 21:23:48
Saw my new Psychiatrist today. To make a long story short, he said he wanted to refer me to his medical director as my case was above his head. At least he was honest.......
O.k., so here goes: I've posted before and the Serzone I take, now down to 300mg from 400mg just wasn't working anymore. I tried to go to 450mg first, but it made my anxiety and depression worse.
The first time I tried Lexapro, I had weaned down to 75mg bid on the Serzone and had a lift from my depression and experienced terrible headaches and Nausea at the time. I definately noticed that I couldn't cry and was getting the numb feeling, which I wish I had back now in hindsight. My doctor at the time told me to go back on the Serzone back to 400mg, so I did, but it just pooped out or something and doesn't do anything but give me withdrawal as I come down.
I have since tried the Lexapro about 4-5 times with the Serzone at 400mg, but it gives me terrible flu like symptoms on or about day 5 or 6 and I have to stop. But even so, for those few days, I feel the lift in my mood, energy, and decreased anxiety.
For the past two days, I've taken 1.25mg of Lexapro, thats a 5mg tab cut into 1/4's. And again, I'm feeling better. I've done this before at this dose and still get unbearable flu like symptoms on or around days 4-7.
So here is my question:
Serzone blocks 5HT2a receptors and Noradrenaline reuptake. I've read that it has no affinity for Serotonin receptors and other sites say it has a small affinity of blocking the reuptake of Serotonin. I thought it just turned off the autoreceptor.
Serzone is metaboblozid by Cytochrome 2D6 and 3a.
Lexapro of course blocks the reuptake of Serotonin at 5HT1a receptors, and is metabolized by 2D6 and 2C19.
I also take Metoprolol and this is metabolized by 2D6 as well.
My last drug is Xanax, which I take prn and is Metabolized by 2C19.
So here is my question: ????????????
Why do I get so sick that I have to stop the Lexapro on day 4,5,6 or 7 ? Is the fact that 2D6 enzyme is being used for all three of my meds and the plasma concentration of the Lexapro getting higher? or is it possible that the Serzone plasma concentrations are getting to high ? I found an article that stated that metoprolol plasma concentrations double when taking lexapro due to the 2D6 enzyme.
http://www.inhousepharmacy.com/anti-depres...nformation.htmlEffects of escitalopram on other drugs in vivo
Co-administration with desipramine (a CYP2D6 substrate) resulted in a twofold increase in plasma levels of desipramine. Therefore, caution is advised when escitalopram and desipramine are co-administered. A similar increase in plasma levels of desipramine, after administration of imipramine, was seen when given together with racemic citalopram.
Co-administration with metoprolol (a CYP2D6 substrate) resulted in a twofold increase in the plasma levels of metoprolol. However, the combination had no clinically significant effects on blood pressure and heart rate.
I have tolerated imipramine and prilosec in the past (both broken down by 2C19, so I doubt I have a problem with this particular enzyme). Which leads me back to the 2D6 issue.
Unless I get plasma levels of each drug, I won't know if this is causing my problem, but given the fact that I respond well to the lexapro even at low doses, it shows that it is partially working for me. I think this is somehow augmenting with the Serzone and thats why I feel what I feel even at 1.25mg of Lexapro which is way subtherapeutic according to dosing literature. My problem is the Director can't see me for two more weeks, so I have time to try and get this right in the meantime. I was having terrible crying spells daily for the last month. When I introduced the Lexapro at 1.25, later that same day, the crying spells went away and have been gone x 3 days now, and I'm feeling much better overall. My anxiety is even down too. Nothing else has changed. It's just a matter of a few more days before I start feeling sick.
Gary
Posted by garyengelm on January 3, 2008, at 21:28:08
http://www.inhousepharmacy.com/anti-depressants/lexapro-information.html
Posted by seldomseen on January 3, 2008, at 21:32:58
In reply to Pharmacogenetic and Receptor Question, posted by garyengelm on January 3, 2008, at 21:23:48
so, before I give my opinion on your symptoms, could you elaborate on the flu-like symptoms you experience a bit?
Do you get a fever? Achy all over? Tender to the touch type thing?
Posted by garyengelm on January 3, 2008, at 21:43:22
In reply to Re: Pharmacogenetic and Receptor Question, posted by seldomseen on January 3, 2008, at 21:32:58
terrible body aches, nausea to the point of gagging, I'm not one to actually vomit, but if I was, I would be vomiting. The chills like you get with the flu with shivering even next to a warm fireplace. Just feel like crap. All that, yet no fever.
Posted by Phillipa on January 3, 2008, at 23:57:57
In reply to Pharmacogenetic and Receptor Question, posted by garyengelm on January 3, 2008, at 21:23:48
Does sound like a difficult case is the pschiatrist or director a psychopharmacologist. I don't understand all the enzymes so I can't help there. Did you pdoc have a recommendation for you til you see the medical director? Phillipa
Posted by Phillipa on January 4, 2008, at 0:09:27
In reply to Re: Pharmacogenetic and Receptor Question, posted by Phillipa on January 3, 2008, at 23:57:57
Have you had all current blood work also? Could xanax be involved I though you said you took it prn may be mistaken. Phillipa
Posted by seldomseen on January 4, 2008, at 4:15:26
In reply to Re: Pharmacogenetic and Receptor Question, posted by garyengelm on January 3, 2008, at 21:43:22
Why were you taking the prilosec?
Posted by garyengelm on January 4, 2008, at 7:05:11
In reply to Re: Pharmacogenetic and Receptor Question » garyengelm, posted by seldomseen on January 4, 2008, at 4:15:26
Prilosec in the past for GI problems
Posted by linkadge on January 4, 2008, at 13:47:59
In reply to Pharmacogenetic and Receptor Question, posted by garyengelm on January 3, 2008, at 21:23:48
>Serzone blocks 5HT2a receptors and Noradrenaline >reuptake. I've read that it has no affinity for >Serotonin receptors and other sites say it has a >small affinity of blocking the reuptake of >Serotonin. I thought it just turned off the >autoreceptor.
From what I understand from doing a search on http://pdsp.med.unc.edu/pdsp.php
Serzone is a moderate serotonin uptake inhibitor, weaker than most SSRI's, but still this is present. It acts as an agonist at 5-ht1a, an antagonist at 5-ht2a/c. It is a little weaker a norepinephrine reuptake inhibitor than a serotonin uptake inhibitor. It also posesses antihistamine effects.
>Lexapro of course blocks the reuptake of >Serotonin at 5HT1a receptors, and is metabolized >by 2D6 and 2C19.Lexapro has no particular affinity for 5-ht1a that I know of, it is a releativly selctive serotonin uptake inhibitor with little affinity for other neurotransmitter sites.
>So here is my question: ????????????>Why do I get so sick that I have to stop the >Lexapro on day 4,5,6 or 7 ?
Probably because GI disturbance and nausia are well documented side effects. These side effects tend to decrease over time, but sometimes require discontinuation. SSRI's can activate 5-ht3 receptors in the stomach and cause nasty nausia for some people.
>Is the fact that 2D6 >enzyme is being used for >all three of my meds and the plasma >concentration of the Lexapro getting higher? or >is it possible that the Serzone plasma >concentrations are getting to high ? I found an >article that stated that metoprolol plasma >concentrations double when taking lexapro due to >the 2D6 enzyme.Possibly, I'm not too up on interactions of metabolism. Lexapro has a slight inhibitory effect on the 2d6 enzyme which might increase the levels of one of the metabolites of serzone, or metoprolol, but I can't see that causing nausia. I can't find that lexapro is itself metabolized by cyp-2d6.
Linkadge
Posted by linkadge on January 4, 2008, at 13:51:31
In reply to Re: Pharmacogenetic and Receptor Question, posted by garyengelm on January 4, 2008, at 7:05:11
You could also try a different SSRI with a different pathway of metabolism to see if it is the lexapro.
Certain serotonergic side effects may also depend on what varient of the serotonin transporter gene you have. One study showed that those with the SS varient of this gene got all the nausia and side effects. Although, no convinent way to test for that at this point.My mother, for instance, had so much nausia and vomiting on paxil that she needed to quit, (she wasn't taking anything else at the time).
Linkadge
This is the end of the thread.
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