Paxil Doesn't Work Anymore---What's Next?

TCASII, ADN · May 6, 2005

I've been on almost everything one can think of. Prozac, Paxil, Zoloft, Celexa, Lexapro, Effexor, Tofranil (imipramine), Pamelor (nortriptyline), Wellbutrin, Serzone (nefazodone), and now Cymbalta.

Paxil was the first and only AD that really changed things for me. My depression, anxiety, and migraines were 90% gone! Then tachyphylaxis set in after only one year.

Tried a myriad of ADs and augmentations that never really worked. The closest I got was with Effexor, however, it was only about a 50% reduction in depression, 20% reduction in anxiety, but did work for the migraines.

Just started Cymbalta (duloxetine) at 20 mg qd, but I'm not much different than I was on Effexor. Only real difference is my appetite is better. Next visit to my rheumy, I'm gonna ask for a step up. My psych isn't willing to let me try anything else since he thinks Effexor is working. Well, it did 5+ years ago when I started it, but not now.

Bottom line, no one can really tell you what will work and what won't. Celexa and Lexapro seem to be tolerated well, but no guarantees. They were like candy when I took them. I just need something strong, and Paxil is the most potent 5-HT reuptake inhibitor out there still. Cymbalta seems to be close in its Ki values, but it's very new, so no definite answer there. For an idea of how strong Paxil is, it's 23 times more potent than Prozac at blocking the uptake of 5-HT, and 7 times more potent than Zoloft. Just depends on how much 5-HT and/or NE increase you might need. Combine that with tolerance to the drug and other factors, and it gets frustrating for us who need them.

NurseFirst · May 6, 2005

Cymbalta seems to be close in its Ki values, but it's very new, so no definite answer there. For an idea of how strong Paxil is, it's 23 times more potent than Prozac at blocking the uptake of 5-HT, and 7 times more potent than Zoloft. Just depends on how much 5-HT and/or NE increase you might need. Combine that with tolerance to the drug and other factors, and it gets frustrating for us who need them.

What is a Ki value??

I thought I knew about pharmacology--and about anti-depressants in particular...but I've not heard of a Ki value before!!! (The only "ki" I know about it is the one from Chinese medicine, Tai Chi, etc.)

As for the OP's concerns--

1) everyone reacts differently to antidepressants, as you can see by the various reactions that posters on this thread have had.

2) highly recommend that you be followed by a "pdoc" (psychiatrist) rather than a family practitioner

3) support groups can be very helpful--the one I was a member of back before there was a web was "walkers-in-darkness" -- you can find them at http://www.walkers.org They have online chats, email chats, bulletin board type chats.

4) When I belonged to walkers the first time there was a wonderful pdoc who joined us for a while, Dr. Ivan Goldberg. He has a website, I think it's

http://www.depressioncentral.com . You might try looking there, too.

Best Regards,

NurseFirst

thn5625 · May 6, 2005

Did running help you better than the drugs. I take lexapro with hardly any side effects but I rather go natural. Do you think it maintains the serotin level just as well as medication. I also know someone who does this. I didnt believe her at first but now youre the second person whos saying this.

I've tried various antidepressants but could not stand the side effects. The only thing that works for me is running 3 times a week. I don't do long distance - a mere 2.5miles on a soft path with good quality shoes and I love the side effects! I realize not everyone can run but there are other options. Walking is okay but I have found in order to change my brain chemistry I need something more intense.
Good luck.

thn5625 · May 6, 2005

I also experienced vivid dreams initially taking prozac and also lexapro. It goes away I somewhat. Although sometimes I dream of something and it goes in my memory as it already happened. Recently, I was dreaming of playing football. As I went for a tackle in my dream I woke up hitting my head on the corner of wood. I realized that I was enacting the tackle while I was sleeping. My eye is now bruised!!

I'm on 60 mg of Celexa. If you can get passed the few weeks when you first start it where you cannot stay awake (I realize this isn't an option for everyone) then I'd recommend it. Every time I've upped my dosage, and when I first start it, I have the most incredible, vivid dreams and I can't tell when I'm awake or asleep. It's weird. Anyone else experience this?
Also, sometimes I feel foggy and unalert. Is this due to the medicine? I can't compare to what I felt like before, because I was in such a deep depression my mind didn't work right then either, but this fogginess gets really frustrating when I have a test to take. Like I bombed my last Chemistry quiz just because I was feeling fuzzy. I have an appointment with my doctor to discuss what I should do about my medicine. Are there any antidepressants that wouldn't make me feel fuzzy or foggy? It's not all the time, just occasionally, but it's bothersome.

TCASII, ADN · May 6, 2005

What is a Ki value??
I thought I knew about pharmacology--and about anti-depressants in particular...but I've not heard of a Ki value before!!! (The only "ki" I know about it is the one from Chinese medicine, Tai Chi, etc.)

The Ki value is used to determine receptor-ligand affinity for any drug with certain tissues. K is the equilibrium constant, and the subscript "i" represents inhibition a competing chemical has over a radioligand. Basically, Ki values give researchers the affinities chemicals have for specific receptors and transporters, and how much inhibition is associated. The lower the Ki value the higher the affinity.

In human cloned tissue specific to serotonin (5-HT) activity with 5-HT transporters, paroxetine (Paxil) is less than 1 nmol/L in nearly every assay performed to date. Some values for Paxil are 0.06, 0.10, 0.34, and 0.83. The numbers vary simply because of the tissue and controls used. Paxil is > 100 and

Venlafaxine (Effexor) averages around 70 Ki. One study from 1997 has it at 7.5 nmol/L, but it's the only one below 70.

This is done for nearly all chemicals, not just ADs or psychiatric meds. Ondansetron (Zofran), the anti-emetic has a Ki of around 7.0 for the 5-HT3 receptor located in the gut, however, all the other 5-HT receptor subtypes and dopamine receptors tested the Ki was >10,000. So it has no clinically significant affinity for those receptors, just the 5-HT3 receptor subtype.

hikernurse · May 6, 2005

Did running help you better than the drugs. I take lexapro with hardly any side effects but I rather go natural. Do you think it maintains the serotin level just as well as medication. I also know someone who does this. I didnt believe her at first but now youre the second person whos saying this.

I'll be the third person :). At least it takes the edge off. My friend, a psychiatrist, doesn't think that for most people it will do enough, but I've found that it can make a real difference. I think that it would depend on the person's biochemistry, but I know my head is alot less tangled when I get a few runs in a week. Besides, it's good for your heart :redbeathe.

Long Term Care Columnist / Guide · May 6, 2005

Whew! This is some really great information........thanks to you all!! :bowingpur

Now, here's one for those of you on Paxil CR: Is this any better than regular Paxil? I'd like to stick with the same medication, if at all possible, because I've never had any problems with it, other than some weight gain in the beginning and some bizarre sensations whenever I was out of the stuff for more than a day or two. (Withdrawal is REAL and it's really strange..... :uhoh21: )

Thanks again for all the wonderful input. I agree that I'd do well to get some talk therapy in, too, as well as a light box and some visits to the tanning salon during the looooooong gray months.

NurseFirst · May 6, 2005

The Ki value is used to determine receptor-ligand affinity for any drug with certain tissues. K is the equilibrium constant, and the subscript "i" represents inhibition a competing chemical has over a radioligand. Basically, Ki values give researchers the affinities chemicals have for specific receptors and transporters, and how much inhibition is associated. The lower the Ki value the higher the affinity.
In human cloned tissue specific to serotonin (5-HT) activity with 5-HT transporters, paroxetine (Paxil) is less than 1 nmol/L in nearly every assay performed to date. Some values for Paxil are 0.06, 0.10, 0.34, and 0.83. The numbers vary simply because of the tissue and controls used. Paxil is > 100 and
Venlafaxine (Effexor) averages around 70 Ki. One study from 1997 has it at 7.5 nmol/L, but it's the only one below 70.
This is done for nearly all chemicals, not just ADs or psychiatric meds. Ondansetron (Zofran), the anti-emetic has a Ki of around 7.0 for the 5-HT3 receptor located in the gut, however, all the other 5-HT receptor subtypes and dopamine receptors tested the Ki was >10,000. So it has no clinically significant affinity for those receptors, just the 5-HT3 receptor subtype.

Cool!!!! Thanks for the info!!!

Right now my brain is full of cipro information because I'm taking it--what a pain in the butt drug. Don't eat Ca this many hours before this many hours after taking it...and zine, and iron--and don't drink too much caffeine or eat too much chocolate -- and that's just the PATIENT information :)

For those folks asking about exercise--my pdoc used to distribute a flyer that had non-pharmacological methods for treating mild to moderate depression. Walking, or exercise, was on the top of the list (remember the term "runner's high"?). Light therapy was another; SAMe was another. And, of course, don't discount talk therapy -- such as cognitive therapy, which has been shown in studies to be as effective as an anti-depressant.

NurseFirst

Long Term Care Columnist / Guide · May 6, 2005

You know, I was just thinking about the exercise component........I know from personal experience that it DOES work. Last spring and summer, I worked out almost every day, and I felt better than I had since I was a young girl.

What happens, though, is autumn comes, and then I don't want to be outside anymore because it's wet and chilly, and indoor exercise gets boring after awhile, and then the gray moods set in along with the gray skies, and then I eat every warm carbohydrate I can find!! That in turn leads to weight gain, which makes me even MORE down in the dumps, not only because I feel guilty for eating too much but because sugar really affects my moods. I feel best when I don't eat any sweets other than fruit, but it's SO difficult to avoid all sweets entirely........I managed it for a full 8 months last year, but lost control in the early fall when my schedule changed from 3-11 to 11A-7P. (I'm still not sure why that was, except day shift is SO crazy and I often don't get a lunch break until four or five hours into the shift, if at all, so it's easier to grab whatever's available to prevent the blood-sugar crashes and the inevitable irritability that follows.)

At least I've identified some major sources of the problem; that's half the battle, right? Now, if I can just figure out how to FIX it........

**RosesrReder, BSN, MSN, RN** · May 6, 2005

I've been on this drug for 4 years, and until recently it's served me well. Now it doesn't seem to be doing its job anymore, and I'm already at close to the maximum dosage (I'm taking 40mg QD, and I think the highest safe dose is 50mg).
Now, I know there's a whole wide world of antidepressants, and newer ones than what I'm taking.......which one(s) do you guys think is the best, and tell me what you like about it? I want to have some solid information before I go to my PCP and ask him to switch me to something else.
Thanks!

MY MOTHER RECENLTY WENT TO HER DR. WITH THE SAME CONCERN. SHE CLAIMS THAT HER PAXIL ISN'T WORKING ANYMORE. HER DR. PUT HER ON WELLBUTRIN SR, SHE CLAIMS SHE FEELS MUCH BETTER AND THAT IT IS WORKING WELL FOR HER. YOU MIGHT WANT TO TALK TO YOUR DR. ABOUT IT.

GOOD LUCK, :)

JESSY

lsyorke, RN · May 6, 2005

Paxil and Paxil CR are virtually the same thing. The CR version delays release by .8-4.8 hours due to different binders in the pill. These binders also inhibit the active ingredient so paxil cr 25 mg is equal to paxil regular 20mg. CR isn't truely a "time released" pill since the dosing is the same,unlike a true time released cap like Cardizem cd where the dose is 240mg vs regular cardizem 60mg. CR was marketed when the exclusivity on paxil regulars patent was running out.

hollyster · May 6, 2005

My Dr. put me on Cymbalta to help with pain control. It has been wonderful. I have never been able to tolerate ADs but I have not had one side effect with this and it is helping my ability to tolerate the pain.